StudyFinder
Search Results Within Category "Cancer - Other Solid Tumors"
18 Study Matches
VITAS: Atezolizumab in Combination With Chemotherapy for Pediatric Relapsed/Refractory Solid Tumors
- cancer@cchmc.org
ALL
6 months to 30 years old
PHASE1
NCT04796012
Inclusion Criteria:
• Signed informed consent
• Relapsed or refractory solid tumor after at least one prior course of therapy.
• Hodgkin lymphoma or non-Hodgkin lymphoma are not permitted.
• Patients with CNS malignancy or asymptomatic CNS metastases may be enrolled, provided all of the following criteria are met. * No metastatic or primary disease affecting the brainstem, midbrain, pons, or cerebellum, or within 10 mm of optic nerve * No history of leptomeningeal disease * No history of intracranial or spinal cord hemorrhage * No evidence of progression of neurologic deficit, in the investigator's judgment, within 7 days prior to initiation of study medications.
• Must have histologically confirmed rhabdomyosarcoma (RMS) for RMS efficacy cohort.
• Age ≥ 6 months and ≤ 30 years
• Lansky Performance Status (patients \< 16 years old) or Karnofsky Performance Status (patients ≥ 16 years old) ≥ 50
• Ability to comply with the study protocol, in the investigator's judgment
• For RMS efficacy cohort, disease must be measurable as defined by RECIST v1.1.
• For the feasibility cohort, disease must be evaluable, but patients enrolled in the feasibility cohort will be prospectively assessed for measurable disease, RMS patients will also be included in the RMS efficacy cohort.
• Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation.
• Availability of a tumor specimen suitable for determination of PD-L1 status, either from initial diagnosis or from a recurrence.
• For PD-L1 staining to be performed at the central site, a formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 15 slides containing unstained, freshly cut, serial sections must be available along with an associated pathology report prior to study enrollment.
• Patients for whom the required number of slides are not available may still be eligible to enroll on study with PI approval
• For the RMS efficacy cohort, it will be required that at least 8 of 17 patients have PD-L1(+) tumor. PD-L1 status will be determined at time of enrollment for all patients. When the maximum allowable number of PD-L1(-) patients has been enrolled and treated on study, PD-L1 positivity will be required for all further enrolled patients.
• Staining will be performed in the central site CAP/CLIA-certified laboratory using the 22c3 antibody for immunohistochemical analysis
• PD-L1(+) status will be defined as staining on ≥1% of tumor cells or ≥1% of stroma.
• For the feasibility cohort, PD-L1 positivity is not required but will be performed centrally in all cases for exploratory biomarker studies.
• Adequate organ and marrow function as defined by the following laboratory values obtained within 21 days prior to initiation of study medication.
• For patients without known bone marrow involvement: * Absolute neutrophil count ≥ 1.0 x 10\^9 / L (1000/µL) without granulocyte colony-stimulating factor support (≥14 days after the last dose of a long-acting growth factor such as pegfilgrastim, or 7 days after short-acting growth factor) * Platelet count ≥ 75 x 10\^9 / L (75,000/µL) without transfusion in the last 7 days
• Patients with known bone marrow metastatic disease will be eligible for the study if they meet the following criteria: * Patients with documented liver metastases: AST and ALT ≤ 5 x ULN * Patients with documented liver or bone metastases: ALP ≤ 5 x ULN * Absolute neutrophil count (ANC) ≥ 750/mm\^3 * Platelet count ≥ 50,000/mm\^3 (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions) * These patients will not be evaluable for hematologic toxicity. At least 4 of 6 patients in the feasibility cohort must be evaluable for hematologic toxicity. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity.
• Total bilirubin ≤1.5 x upper limit of normal (ULN) for age (Patients with known Gilbert disease: serum bilirubin ≤ 3 x ULN)
• AST (SGOT) and ALT (SPGT) ≤ 2.5 x ULN for age
• Serum albumin ≥ 25 g/L (2.5 g/dL)
• Creatinine ≤ 1.5 x ULN for age or creatinine clearance (or radioisotope glomerular filtration rate) ≥ 70 mL/min/1.73 m2
• Left ventricular ejection fraction ≥ 50% or shortening fraction ≥ 30%
• Hemoglobin ≥ 90 g/L (9 g/dL)
• Patients may be transfused to meet this criterion.
• For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• Negative HIV and hepatitis B surface antigen (HBsAg) tests at screening
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as defined below:
• Women must remain abstinent or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for 5 months after the final doses of atezolizumab, vincristine, and temozolomide. Women must refrain from donating eggs during this same period.
• A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus), regardless of sexual orientation or marital status.
• Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
• The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception.
• For men who are not surgically sterile: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
• With a female partner of childbearing potential who is not pregnant, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of less 1% per year during the treatment period and for 5 months after the final doses of atezolizumab, irinotecan, and temozolomide. Men must refrain from donating sperm during this same period.
• The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception
Exclusion Criteria:
• Pregnancy or breast-feeding:
• Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of study treatment
• Women of childbearing potential must have a negative serum pregnancy test result within 21 days prior to initiation of study treatment.
• Medical conditions that are excluded:
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Guillain-Barré syndrome, multiple sclerosis, or Kawasaki syndrome with the following exceptions: * Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study. * Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study. * Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met at study initiation: (1) Rash must cover less 10% of body surface area, (2) Disease is well controlled at baseline and requires only low-potency topical corticosteroids, (3) No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
• Uncontrolled or symptomatic hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL or corrected serum calcium \> ULN)
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) * Patients with indwelling catheters (e.g., PleurX®) are allowed.
• Uncontrolled tumor-related pain * Patients requiring pain medication must be on a stable regimen at study entry for at least 2 weeks. Intermittent use of as-needed medication is allowed during this period.
• Clinically significant gastrointestinal disorder that may interfere with absorption of orally administered drugs (at the discretion of the treating physician)
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan * History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
• History of severe asthma or uncontrolled asthma
• Dyspnea at rest or requirement for supplemental oxygen
• Uncontrolled seizures. Patients taking a stable dose of anticonvulsants (for 2 weeks) are permitted, as long as they are not strong inducers or inhibitors of CYP3A4.
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications in the opinion of the treating investigator
• Washout periods from prior therapies:
• Myelosuppressive chemotherapy or radiotherapy within 21 days prior to starting study treatment. * Subjects must have recovered from all acute prior treatment-related toxicities to grade 1 or baseline (excluding alopecia and clinically stable toxicities requiring ongoing medical management, such as hypothyroidism).
• Non-myelosuppressive cancer therapy, such as kinase inhibitors, within 7 days prior to study treatment.
• Treatment with monoclonal antibodies with long half-lives, within 3 half-lives prior to study treatment.
• Treatment with targeted cellular therapies within 28 days prior to starting study treatment.
• Major surgical procedure, other than for diagnosis, within 30 days prior to initiation of study treatment, or anticipation of the need for a major surgical procedure during the first four cycles of the study. * Biopsy tissue collection or placement of a vascular access device is permitted if the site has healed prior to initiation of study medications. * For patients with CNS disease, no neurosurgical resection, brain biopsy, or stereotactic/whole-brain radiation within 30 days prior to Cycle 1, Day 1
• Treatment with a live, attenuated vaccine within 30 days prior to initiation of study treatment, or anticipation of the need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
• Treatment with investigational therapy within 21 days prior to initiation of study treatment or concurrent participation with another investigational agent
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-agents) within 2 weeks prior to initiation of study treatment, or anticipation of the need for systemic immunosuppressive medication during study treatment, with the following exceptions: * Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Principal Investigator confirmation has been obtained. * Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study. * Patients with CNS disease can be receiving concurrent treatment with corticosteroids with approval from the Principal Investigator. Patients must be receiving a stable or decreasing dose for ≥ 5 days prior to the baseline MRI scan and at the time of drug initiation. The Principal Investigator should be informed when steroid doses are increased because of declining patient status.
• Use of strong CYP3A4 inhibitors or inducers or strong UGT1A1 inhibitors within 12 days of Cycle 1, Day 1.
• Treatment with high-dose chemotherapy and hematopoietic stem-cell rescue within 3 months prior to initiation of study drug
• Treatment with herbal cancer therapy within 1 week prior to initiation of study medications.
• Treatment with a long-acting hematopoietic growth factor (such as pegfilgrastim) within 2 weeks prior to initiation of study medications, or a short-acting hematopoietic growth factor (such as G-CSF) within 1 week prior to initiation of study medications.
• Prior treatments:
• Prior allogeneic stem cell or solid organ transplantation
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies to include all anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\] within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
• Subjects must not have previously progressed while receiving regimens that include irinotecan or temozolomide. Patients who have received irinotecan or temozolomide and did not progress while on these medications are eligible.
• Known ongoing or untreated infection, including, but not limited to bacteremia, active tuberculosis, or severe pneumonia
• Active tuberculosis
• Current treatment with anti-viral therapy for HBV
• Active hepatitis C
• Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study
• Known allergy or hypersensitivity to any component of the study medications
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
DRUG: Atezolizumab, DRUG: Vincristine, DRUG: Irinotecan, DRUG: Temozolomide
Solid Tumor, Rhabdomyosarcoma
Relapsed solid tumor, Refractory solid tumor, Rhabdomyosarcoma
SPEARHEAD-3 Pediatric Study
- cancer@cchmc.org
ALL
2 years to 21 years old
PHASE1
NCT05642455
Inclusion Criteria:
* Subject has histologically confirmed diagnosis of any one of the following cancers: (A) Synovial Sarcoma (SS), (B) MPNST, (C) Neuroblastoma, or (D) Osteosarcoma (OS).
* Age:
(A) Synovial Sarcoma: 2 to 17 years (B) MPNST, Neuroblastoma and Osteosarcoma: 2 to 21 years
* Body weight ≥ 10 kg
* Must have previously received a systemic chemotherapy
* Measurable disease prior to lymphodepletion according to RECIST v1.1 (or INCR, 2017 Neuroblastoma only).
* HLA-A\*02 positive
* Tumor shows MAGE-A4 expression confirmed by central laboratory.
* Performance Status:
(A) Subjects ≥16: Eastern Cooperative Oncology Group (ECOG) 0 or 1 (B) Subjects 2 to 16: Lansky score ≥ 80
• Subject has anticipated life expectancy of greater than 3 months in the opinion of the investigator.
Exclusion Criteria:
* Positive for HLA-A\*02:05 in either allele; or any A\*02 having same protein sequence as HLA-A\*02:05
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide.
* History of autoimmune or immune mediated disease
* Known central nervous system (CNS) metastases.
* Other prior malignancy that is not considered by the Investigator to be in complete remission
* Clinically significant cardiovascular disease
* Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or human T cell leukemia virus
* Pregnant or breastfeeding
* Experiencing ongoing rapid disease progression that in the opinion of the Investigator significantly increases the subjects risk associated with treatment. GENETIC: Afamitresgene autoleucel
Synovial Sarcoma, Malignant Peripheral Nerve Sheath Tumor (MPNST), Neuroblastoma (NBL), Osteosarcoma
CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma
- cancer@cchmc.org
ALL
12 months to 21 years old
PHASE1
NCT04870944
Inclusion Criteria:
* Parts A and B: Patients must be \>= 12 months and =\< 21 years of age at the time of study enrollment
* Patients must have had histologic verification of malignancy at original diagnosis or relapse, except in patients with diffuse intrinsic brain stem tumors, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers, including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
* Part A: Patients with relapsed or refractory solid tumors or lymphoma, including patients with CNS tumors or known CNS metastases (including untreated or progressive) are eligible
* Part B: Patients with progressive or recurrent DIPG (diagnosed by biopsy or imaging characteristics) and other H3 K27-altered DMG previously treated with radiation therapy
* Part A: Patients must have either measurable or evaluable disease
* Part B: Patients must have measurable disease
* Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
* Patients must have a performance status corresponding to Easter Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age. Patients must have a Karnofsky or Lansky score \>= 50%
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
* Solid tumor patients: \>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
* Anti-cancer agents not known to be myelosuppressive (eg, not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days after the last dose of agent
* Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1
* Corticosteroids: If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid. Patients with CNS tumors receiving corticosteroids must have been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment
* Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
* Stem cell Infusions (with or without total body irradiation \[TBI\]):
* Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: \>= 84 days after infusion and no evidence of graft versus host disease (GVHD)
* Autologous stem cell infusion including boost infusion: \>= 30 days
* Cellular therapy: \>= 42 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.)
* Radiation therapy \[XRT\]/external beam irradiation including protons: \>= 14 days after local XRT; \>= 150 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow (BM) radiation
* Radiopharmaceutical therapy (e.g., radiolabeled antibody, I-131 metaiodobenzylguanidine \[131I MIBG\]): \>= 42 days after systemically administered radiopharmaceutical therapy
* Patients must not have received prior exposure to CBL0137
* For patients with solid tumors without known bone marrow involvement:
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
* For patients with solid tumors without known bone marrow involvement:
* Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a creatinine based on age/sex as follows (performed within 7 days prior to enrollment unless otherwise indicated):
* Age: Maximum serum creatinine (mg/dL)
* 1 to \< 2 years: 0.6 (male); 0.6 (female)
* 2 to \< 6 years: 0.8 (male); 0.8 (female)
* 6 to \< 10 years: 1 (male); 1 (female)
* 10 to \< 13 years: 1.2 (male); 1.2 (female)
* 13 to \< 16 years: 1.5 (male); 1.4 (female)
* \>= 16 years: 1.7 (male); 1.4 (female)
* Patients with solid tumors:
* Bilirubin (sum of conjugated + unconjugated or total) =\< 1.5 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with solid tumors:
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L (performed within 7 days prior to enrollment unless otherwise indicated)
* Shortening fraction of \>= 27% by echocardiogram (performed within 7 days prior to enrollment unless otherwise indicated) or
* Ejection fraction of \>= 50% by gated radionuclide study (performed within 7 days prior to enrollment unless otherwise indicated)
* Corrected QT (QTC) \< 480 msec (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with seizure disorder may be enrolled if seizures well controlled without the use of enzyme-inducing anti-convulsant agents. Well controlled is defined by no increase in seizure frequency in the prior 7 days
* Nervous system disorders (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]5) resulting from prior therapy must be =\< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
* Patients have consented to receive a central venous catheter prior to the administration of CBL0137. A central line is required for CBL0137 administration
Exclusion Criteria:
* Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control
* Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Patients who are currently receiving another investigational drug are not eligible
* Patients who are currently receiving other anti-cancer agents are not eligible (except leukemia patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy)
* Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
* Patients who are receiving drugs that are strong inducers or inhibitors of CYP3A4, CYP2B6 (e.g., carbamazepine) and CYP1A2 (e.g., ciprofloxacin, enoxacin, fluvoxamine, smoking) are not eligible. These agents are to be avoided for 7 days prior to the start of CBL0137 and for the duration of the protocol therapy. Sensitive substrates of CYP2D6 (e.g., atomoxetine, desipramine, dextromethorphan, eliglustat, nebivolol, nortriptyline, perphenazine, tolterodine, R-venlafaxine) should also be avoided for the duration protocol therapy
* Patients who are receiving drugs associated with a known risk of Torsades de Pointes (TdP) are not eligible. Drugs associated with known risk of Torsades de Pointes (TdP) are to be avoided for 7 days prior to the start of CBL0137 and for duration of the protocol therapy
* Patients with known peripheral vascular disease are excluded
* Patients with a history of pro-thrombotic disorder are not eligible
* Patients who have an uncontrolled infection are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspirate, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Echocardiography Test, DRUG: FACT Complex-targeting Curaxin CBL0137
Diffuse Midline Glioma, H3 K27-Altered, Metastatic Malignant Neoplasm in the Central Nervous System, Recurrent Diffuse Intrinsic Pontine Glioma, Recurrent Diffuse Midline Glioma, H3 K27-Altered, Recurrent Lymphoma, Recurrent Malignant Solid Neoplasm, Recurrent Primary Malignant Central Nervous System Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Primary Malignant Central Nervous System Neoplasm
NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
cancer@cchmc.org
ALL
Up to 30 years old
PHASE1
NCT06239272
Inclusion Criteria:
Inclusion Criteria - All Patients
* Patients must be 1-30 years at the time of the biopsy that established the diagnosis of NRSTS.
* Surgical Resection: Patients who had an upfront resection prior to enrollment will be eligible if they are able to begin therapy within 28 days of resection assuming other eligibility criteria are met. Delayed resection is preferred for all patients with intermediate and high-risk disease.
* Lansky performance status score ≥ 60 for patients ≤ 16 years of age. Karnofsky performance status score ≥ 60 for patients \>16 years of age. Note patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
Diagnosis
• Patients with CIC-DUX 4 rearranged sarcomas will be enrolled on the high-risk stratum only, regardless of presence of metastasis, size, or resection status.
Patient has low-risk disease if the patient has a:
* Low-grade tumor of any size where R0 or R1 surgical margins are anticipated or achieved.
* High-grade tumors that are \< 5 cm where R0 or R1 resection margins are anticipated or achieved.
Patient must have adequate organ function in the organs that will be within the radiotherapy field.
Adequate renal function defined as:
* Creatinine clearance or radioisotope GFR \> 70 mL/min/1.73 m2, or
* A normal serum creatinine based on age/gender as follows
Age Maximum Serum Creatinine (mg/dL) Male Female 2 to \< 6 years 0.8 0.8 6 to \< 10 years 1 1 10 to \< 13 years 1.2 1.2 13 to \< 16 years 1.5 1.4 \> 16 years 1.5 1.4
Adequate liver function defined as:
* Total bilirubin \< 1.5 x upper limit of normal (ULN) for age
* SGOT (AST) or SGPT (ALT) \< 2.5 x ULN for age
Adequate cardiac function defined as:
* Ejection fraction of \> 55% by echocardiogram or cardiac MRI
* QTc \< 480 msec
Adequate pulmonary function defined as:
* No evidence of dyspnea at rest, no exercise intolerance, and a resting pulse oximetry reading \> 94% on room air if there is clinical indication for determination.
Inclusion Criteria - Intermediate and High Risk Participants
Patient has intermediate-risk if the patient has a:
* Low-grade non-metastatic initially unresectable disease at study enrollment where delayed resection is planned.
* High-grade \< 5 cm non-metastatic initially unresectable disease at study enrollment where delayed resection is planned. Of note, patients enrolled on the low-risk arm who were unable to achieve gross total resection where delayed re-resection is planned are eligible for this arm.
* High-grade tumor \> 5 cm that is potentially resectable.
Patient high-risk if the patient has:
* Metastatic disease at presentation
* Unresectable disease at study enrollment where delayed resection is not anticipated. Of note, patients enrolled on the low-risk arm who were unable to achieve gross total resection where delayed re-resection is not-planned are eligible for this arm.
* CIC-DUX4 rearranged sarcoma
Organ Function
Adequate bone marrow function defined as:
* Absolute neutrophil count \> 1000/µL
* Platelet count \> 100,000/µL
* Hemoglobin \> 8 g/dL for patients \< 16 years of age
* Hemoglobin \> 9 g/dL for patients \> 16 years of age
Note: No transfusions are permitted 7 days prior to laboratory studies to determine eligibility.
Adequate renal function defined as:
* Creatinine clearance or radioisotope GFR \> 70 mL/min/1.73 m2, or
* A normal serum creatinine based on age/gender as follows
Age Maximum Serum Creatinine (mg/dL) Male Female 2 to \< 6 years 0.8 0.8 6 to \< 10 years 1 1 10 to \< 13 years 1.2 1.2 13 to \< 16 years 1.5 1.4 \> 16 years 1.5 1.4
Adequate liver function defined as:
* Total bilirubin \< 1.5 x upper limit of normal (ULN) for age
* SGOT (AST) or SGPT (ALT) \< 2.5 x ULN for age
Adequate cardiac function defined as:
* Ejection fraction of \> 55% by echocardiogram or cardiac MRI
* QTc \< 480 msec
Adequate pulmonary function defined as:
* No evidence of dyspnea at rest, no exercise intolerance, and a resting pulse oximetry reading \> 94% on room air if there is clinical indication for determination.
Anticoagulation
Patients on low molecular weight heparin, warfarin (with a stable INR), or direct oral anticoagulants (DOAC) who have been on a stable dose of are eligible. Patients being treated for a pulmonary embolism or deep venous thrombosis (DVT) must have been treated for a minimum of 6 weeks prior to starting therapy treatment.
Life Expectancy
Patient must have a life expectancy of at least 3 months with appropriate therapy.
Exclusion Criteria:
* Patients with known primary CNS sarcoma or CNS metastases are not eligible. Note: Brain imaging is not an eligibility requirement. Tumors with intracranial extension will be allowed.
* Patients with the following histologic diagnosis are not eligible: intermediate locally aggressive tumors as defined by WHO, malignant rhabdoid tumor, alveolar soft part sarcoma, infantile fibrosarcoma, unresectable/metastatic dermatofibrosarcoma protuberans, inflammatory myofibroblastic tumor, desmoid fibromatosis, rhabdomyosarcoma, desmoplastic small round cell tumor, BCOR-CCNB3 fusion positive sarcoma.
* Bleeding diathesis: Patients with evidence of active bleeding or bleeding diathesis will be excluded (Note: Patients aged \> 17 years with excess of 2.5 mL of hemoptysis are not eligible).
* Uncontrolled hypertension: Patients with uncontrolled hypertension (CTCAE v5 Grade ≥ 2) are ineligible. Hypertension must be well controlled on stable doses of medication for at least two weeks.
Prior Therapy
* Patients must have had no prior systemic therapy for the treatment of the NRSTS
* Patients must have had no prior anthracycline or ifosfamide chemotherapy
* Patients must have had no prior use of pazopanib or similar multi-targeted TKI.
Patients must have had no prior radiotherapy to tumor-involved sites.
Note: Patients previously treated for a non-NRSTS cancer are eligible provided they meet the prior therapy requirements. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier are excluded.
* CYP3A4 Substrates WITH Narrow Therapeutic Indices: Patients chronically receiving medications known to be metabolized by CYP3A4 and with narrow therapeutic indices within 7 days prior to study enrollment, including but not limited to pimozide, aripiprazole, triazolam, ergotamine and halofantrine are not eligible. Note: the use of fentanyl is permitted.
* CYP3A4 Inhibitors: Patients chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment, including but not limited to itraconazole, clarithromycin, erythromycin, many NNRTIs, diltiazem, verapamil, and grapefruit juice are not eligible.
* CYP3A4 Inducers: Patients chronically receiving drugs that are known potent CYP3A4 inducers within 14 days prior to study enrollment, including but not limited to carbamazepine, phenobarbital, phenytoin, rifampin, and St. John's wort are not eligible (with the exception of glucocorticoids).
* Certain medications that are associated with a risk for QTc prolongation and/or Torsade's de Pointes, although not prohibited, should be avoided or replaced with medications that do not carry these risks, if possible.
* Subjects with any condition that may impair the ability to absorb oral medications/investigational product including:
* prior surgical procedures affecting absorption including, but not limited to major resection of stomach or small bowel
* active peptic ulcer disease
* malabsorption syndrome
• 4.12 Thyroid Replacement Therapy: Patients who require thyroid replacement therapy are not eligible if they have not been receiving a stable replacement dose for at least 4 weeks prior to study enrollment.
• 4.13 Subjects with any condition that may increase the risk of gastrointestinal bleeding or gastrointestinal perforation, including: * active peptic ulcer disease * known intraluminal metastatic lesions * inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other gastrointestinal conditions which increase the risk of perforation * history of abdominal fistula, gastrointestinal perforation or intra- abdominal abscess within 28 days prior to beginning study treatment.
• 4.14 Pulmonary embolism or DVT. Patients must not have experienced: * An untreated pulmonary embolism or DVT in last 6 months or * treated pulmonary embolism or DVT which has been treated with therapeutic anticoagulation for less than 6 weeks * arterial thrombosis in last 12 months History of serious or non-healing wound, ulcer, or bone fracture. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. HIV-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pazopanib. In addition, these subjects are at increased risk of lethal infections when treated with marrow-suppressive therapy. Patients who are receiving any other investigational agent(s). Pregnancy and Breast Feeding * Pregnancy and Breast Feeding Female patients who are pregnant are ineligible due to risks of fetal and teratogenic adverse events as seen in animal/human studies. * Lactating females are not eligible unless they have agreed not to breastfeed their infants during treatment and for a period of 1 month following completion of treatment. * Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained. * Unwillingness to use an effective contraceptive method for the duration of their study participation and for at least 1 month after treatment is completed if sexually active with reproductive potential.
PROCEDURE: Surgical resection, RADIATION: Proton beam radiation therapy, DRUG: Pazopanib, DRUG: Ifosfamide, DRUG: Doxorubicin, DRUG: Selinexor
Adipocytic Neoplasm, Liposarcoma, Atypical Fibroxanthoma, Angiomatoid Fibrous Histiocytoma, Fibrosarcoma NOS, Myxofibrosarcoma, Angiosarcoma, Osteosarcoma, Extraskeletal, Dedifferentiated Liposarcoma, Myxoid Liposarcoma, Pleomorphic Liposarcoma, Myxoid Pleomorphic Liposarcoma, Low Grade Fibromyxoid Sarcoma, Sclerosing Epithelioid Fibrosarcoma, Malignant Tenosynovial Giant Cell Tumor of Soft Tissue, Epithelioid Hemangioendothelioma, Glomus Tumor, Inflammatory Leiomyosarcoma, Leiomyosarcoma, Ossifying Fibromyxoid Tumor, Malignant, Myoepithelioma, Synovial Sarcoma, Epithelioid Sarcoma, Perineurioma, Malignant, Clear Cell Sarcoma, Extraskeletal Myxoid Chondrosarcoma, Granular Cell Tumor, Malignant, Melanotic Malignant Nerve Sheath Tumor, Malignant Peripheral Nerve Sheath Tumor, Perivascular Epithelioid Tumor, Malignant, Intimal Sarcoma, Myoepithelial Carcinoma, Undifferentiated Sarcoma, Pleomorphic Sarcoma, Undifferentiated, Round Cell Sarcoma, Undifferentiated, NTRK-Rearranged Spindle Cell Neoplasm, Phosphaturic Mesenchymal Tumor, Malignant, Round Cell Sarcoma, Well Differentiated Liposarcoma, Giant Cell Tumor of Soft Parts NOS, Low Grade Myofibroblastic Sarcoma, Dermatofibrosarcoma Protuberans, Fibrosarcomatous
Proton therapy
A Study of Codrituzumab in Children and Young Adults With Solid Tumors and Have Not Responded to Treatment or Have Come Back After Treatment
- cancer@cchmc.org
ALL
1 year to 21 years old
PHASE1
NCT04928677
Inclusion Criteria:
* Consent/Assent: All patients and/or their parents or legally authorized representatives must sign written informed consent; assent, when appropriate, will be obtained according to institutional guidelines.
* Age: Patients must be aged 12 months up to but not including 22 years at the time of study registration. A patient who is 21 at the time of enrollment but turns 22 thereafter will still be considered eligible for the purposes of this study.
Diagnosis:
* Patients must have a diagnosis of a primary extra-cranial solid tumor that is recurrent or refractory to standard therapy.
* For the purposes of this study, the following definitions will be used:
* Refractory is defined as any tumor which progresses despite maximal standard therapies
* Recurrent (relapsed) is defined as a completion of planned therapy after which point the tumor recurs within 5 years of treatment. Additionally, any tumor which recurs twice is considered relapsed.
* Tumor GPC3 Expression: Patients must have demonstrated positive GPC3 expression via immunohistochemistry (IHC) on any prior tumor sample. Confirmation of GPC3 expression may include a diagnostic or relapsed sample, at a primary or metastatic site. There is no limit to how long ago this sample was collected. This GPC3 expression via IHC will be centrally confirmed by Ventana as in prior studies of codrituzumab and described in the treatment. Patients may choose to enroll on the prescreening portion, which allows for assessment of GPC3 expression only, prior to enrollment on the full clinical trial.
* Tumor GPC3 Expression: Patients must have demonstrated a minimum of 1+ GPC3 expression via immunohistochemistry (IHC) on any prior tumor sample. Confirmation of GPC3 expression may include a diagnostic or relapsed sample, at a primary or metastatic site. There is no limit to how long ago this sample was collected. This GPC3 expression via IHC will be centrally confirmed by Ventana as in prior studies of codrituzumab and described in the treatment plan section. Patients may choose to enroll on the prescreening portion, which allows for assessment of GPC3 expression only, prior to enrollment on the full clinical trial.
* Disease Status: Patients must have measurable disease based on RECIST 1.1.
* Performance Level: Patients must have Karnofsky Performance Score (for patients \> 16 years of age) or Lansky Performance Score (for patients ≤ 16 years of age) ≥ 50% assessed within 2 weeks of study enrollment.
* Neurological Deficits: Patients with neurologic deficits must have been stable and off of steroids for a minimum of 1 week prior to study entry; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
* Pregnancy/Contraception: Patients must not be pregnant or breast-feeding; females, excluding pre-menstrual, must have a negative serum or urine pregnancy test within 7 days prior to enrollment; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method, which includes abstinence, for 90 days after the last dose of study drug.
* Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study; recovery is defined as all AEs, attributable to prior therapy, having improved to grade 2 or better or as outlined below. For agents that have known adverse events occurring beyond 28 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair.
* Systemic Anticancer Therapy (e.g. Chemotherapy):
* Not Myelosuppressive: \> 7 days must have elapsed from their last dose of anticancer therapy not known to be myelosuppressive (e.g. not associated with reduced platelet or ANC counts).
* Myelosuppressive: \> 14 days must have elapsed from their last dose of known myelosuppressive anticancer therapy.
* Antibodies: \> 21 days must have elapsed from the infusion of last anticancer antibody.
* Cellular Therapies: \> 42 days must have elapsed from the completion of any type of cellular therapy, including modified T cells, NK cells, dendritic cells, etc.
* Radiation: Patients who have had radiation must have had their last fraction of:
* Local irradiation to the primary tumors or other limited sites (cumulative dose \< 40Gy) \> 14 days prior to registration.
* Local irradiation to the primary tumors or other sites (cumulative dose ≥ 40Gy), therapeutic 131I-MIBG or other radiopharmaceutical, and other substantial bone marrow radiation, \> 42 days prior to registration.
* Craniospinal irradiation, radiation to \> 50% of pelvis, or total body irradiation \> 120 days prior to registration.
* Stem Cell Infusions: With or without TBI
* 84 days must have elapsed from an allogeneic bone marrow or stem cell transplant, or any stem cell infusion including DLI or boost infusion and patients must also not have any evidence of acute or chronic GvHD.
* 42 days must have elapsed from an autologous stem cell infusion including boost infusion.
* Supportive Therapies: Patients must be off all growth factor(s) that support platelet, red blood cell, or white blood cell count, number or function for at least 7 days prior to registration (e.g. filgrastim, sargramostim, erythropoietin, romiplostim, eltrombopag, etc.) as well as off Pegylated G-CSF for at least 14 days prior to registration.
* Organ Function: Patients must have documented within 14 days of registration and within 7 days of starting treatment the following:
* Hgb \> 8 gm/dL (may be transfusion-supported)
* Platelet count \> 50,000/mm\^3 (transfusion independent)
* Absolute neutrophil count (ANC) \> 1000/mm\^3
* INR ≤ 2.5
* Total Bilirubin (sum of conjugated + unconjugated) ≤ 3 times institutional upper limit of normal (ULN) for age
* Aspartate aminotransferase (AST) ≤ 5 times institutional ULN for age
* Alanine Aminotransferase (ALT) ≤ 5 times institutional ULN for age
* Serum albumin ≥ 2 g/dL
* GFR ≥ 50 mL/min/1.73 m\^2 as measured using urine creatinine clearance, serum cystatin c, radioisotope GFR, or serum creatinine as measured by the Schwartz equation (Refer to Schwartz, et al. J Am Soc Neph, 2009)
Exclusion Criteria:
* Patients receiving current anti-cancer therapy or investigational agents are not eligible for study entry.
* Patients who do not have tumor tissue available for GPC3 testing are not eligible for study entry.
* Patients who have received any prior GPC3-directed immunotherapy are not eligible for study entry.
* Patients with uncontrolled seizures are not eligible for study entry.
* Subjects with a condition requiring systemic treatment with either corticosteroids (\>0.15 mg/kg daily prednisone equivalents) or other immunosuppressive medications, if used to modify immune adverse events related to prior therapy, \> 14 days must have elapsed since last dose of corticosteroid or immunosuppressive agent. Inhaled or topical steroids, and adrenal replacement doses ≤ 0.15 mg/kg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
* Patients with documented CNS tumor, CNS metastasis, CNS ischemia and/or infarction, whether symptomatic or discovered incidentally without clinical symptoms, will be excluded from study participation.
* Patients with a baseline QTc \> 480. (as measured using Bazett formula; Refer to Bazett, Heart, 1920).
* Patients with an inability to return for follow-up visits, obtain follow-up studies required to assess toxicity to therapy, or comply with the safety monitoring requirements.
* Patients who have an uncontrolled infection are not eligible.
* Patients who have received a prior solid organ transplantation are not eligible. DRUG: Codrituzumab
Primary Extra-cranial Solid Tumor, Recurrent or Refractory Glypican 3 (GPC3)
Codrituzumab, Hepatoblastoma, 20-489
A Tailored Medication Adherence-Promotion Intervention for Adolescents and Young Adults With Cancer
- cancer@cchmc.org
ALL
15 years to 24 years old
NA
NCT07223463
Inclusion Criteria:
* Patient is 15.00 to 24.99 years of age
* Patient is diagnosed with cancer
* Patient is prescribed an oral anticancer/antitumor agent or prophylaxis
Exclusion Criteria:
* Patient is not fluent in English
* Patient evidences significant cognitive deficits
* Patient's medical status or treatment precludes participation
* Patient enrolled on a medical trial requiring medication storage in a trial-provided container
* Patient demonstrates greater than or equal to 95% adherence during run-in period
* Patient declines to use or has difficulty using electronic adherence monitoring device during run-in BEHAVIORAL: Tailored Program, BEHAVIORAL: Feedback Program (Uniform Standard of Care)
Cancer, Medication Adherence
adolescents and young adults, cancer, adherence
Testing a Standardized Approach to Surgery and Chemotherapy for Type I Pleuropulmonary Blastoma or the Addition of an Anti-cancer Drug, Topotecan, to the Usual Treatment for Types II and III Pleuropulmonary Blastoma
- cancer@cchmc.org
ALL
Up to 21 years old
PHASE3
NCT06647953
Inclusion Criteria:
* 21 years of age or younger
* Newly diagnosed PPB. Note that patients with known germline DICER1 variant or mosaicism with a large, solid unresectable thoracic mass with imaging features characteristic for Type II or III PPB are eligible without histologic confirmation of the diagnosis if a biopsy of the mass is not considered safe or feasible
* Individuals are eligible based on institutional diagnosis of Type I, Ir, II or III PPB diagnosed within 60 days prior to enrollment. Children with Type II or III PPB at risk for clinical decompensation may receive protocol therapy while awaiting rapid central pathology review. Children with Type I or Ir PPB will be assigned to chemotherapy vs. observation based on imaging and central pathology review diagnosis. Type I and Ir patients should not begin chemotherapy prior to return of central pathology results
* For patients with Type II or III PPB (within 7 days prior to enrollment): A serum creatinine based on age/sex as follows:
* Age: 1 month to \< 6 months - Maximum Serum Creatinine (mg/dL): 0.4 (Male), 0.4 (Female)
* Age: 6 months to \< 1 year - Maximum Serum Creatinine (mg/dL): 0.5 (Male), 0.5 (Female)
* Age: 1 to \< 2 years - Maximum Serum Creatinine (mg/dL): 0.6 (Male), 0.6 (Female)
* Age: 2 to \< 6 years - Maximum Serum Creatinine (mg/dL): 0.8 (Male), 0.8 (Female)
* Age: 6 to \< 10 years - Maximum Serum Creatinine (mg/dL): 1 (Male), 1 (Female)
* Age: 10 to \< 13 years - Maximum Serum Creatinine (mg/dL): 1.2 (Male), 1.2 (Female)
* Age: 13 to \< 16 years - Maximum Serum Creatinine (mg/dL): 1.5 (Male), 1.4 (Female)
* Age: ≥ 16 years - Maximum Serum Creatinine (mg/dL): 1.7 (Male), 1.4 (Female) OR - A 24 hour urine creatinine clearance ≥ 60 mL/min/1.73 m\^2 OR - A glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
* Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
* For patients with Type II or III PPB (within 7 days prior to enrollment): Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age
* For patients with Type II or III PPB (within 7 days prior to enrollment): Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) ≤ 135 U/L
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* Shortening fraction of ≥ 27% by echocardiogram, or ejection fraction of ≥ 50% by radionuclide angiogram (within 21 days prior to start of protocol therapy)
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible as long as they are NOT receiving anti-retroviral agents that are strong inhibitors or inducers of CYP3A4
Exclusion Criteria:
* Administration of prior PPB-directed chemotherapy is an exclusion criterion. Prior treatment for another malignancy is not an exclusion criterion
* Patients with known Charcot-Marie-Tooth disease
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met PROCEDURE: Biospecimen Collection, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, BIOLOGICAL: Dactinomycin, DRUG: Dexrazoxane, DRUG: Doxorubicin, PROCEDURE: Echocardiography Test, DRUG: Ifosfamide, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Multigated Acquisition Scan, OTHER: Patient Observation, PROCEDURE: Positron Emission Tomography, DRUG: Topotecan, PROCEDURE: Ultrasound Imaging, DRUG: Vincristine
Pleuropulmonary Blastoma
Lutathera for Treatment of Recurrent or Progressive High-Grade CNS Tumors
- cancer@cchmc.org
ALL
4 years to 39 years old
PHASE1
NCT05278208
All participants must meet the following inclusion and exclusion criteria. No exceptions will be given. Imaging studies to establish eligibility must be done within three weeks prior to enrollment. All other clinical evaluations to establish eligibility (except for \[68Ga\]Ga-DOTATATE PET) must be done within 7 days prior to enrollment.
• Screening Criteria
• 1 Diagnosis Patient must have a diagnosis of primary high-grade CNS tumor (any histopathologic diagnosis that is WHO grade III-IV) or meningioma (any histologic grade) that is recurrent, progressive, or refractory. Note that patients with DIPG (based on radiographic/clinical diagnosis) who have undergone biopsy will be eligible with histologic diagnosis of grade II-IV infiltrating glioma. All tumors must have histologic verification either at the time of diagnosis or recurrence, except for patients meningioma who have not previously undergone biopsy or resection. Note: Refractory disease is defined as the presence of persistent abnormality on conventional MRI that is further distinguished by histology (biopsy or sample of lesion) or advanced imaging, OR as determined by the treating physician and discussed with the primary investigator prior to enrollment.
• 2 Prior Therapy Patients must have recurred/progressed following prior standard therapy for their tumor. Note: Patients with meningioma, atypical meningioma, or anaplastic meningioma must have received at least surgical resection or radiation.
• 3 Screening Consent Participant/legal guardian is willing to sign a screening consent for \[68Ga\]Ga-DOTATATE PET imaging. The screening consent is to be obtained according to institutional guidelines. Assent, when appropriate, will be obtained according to institutional guidelines.
• Eligibility Criteria * Phase I Age Patient must be ≥ 4 and \<12 years of age at the time of enrollment. Disease Status: Patients who participate in the efficacy expansion cohort must have bi-dimensionally measurable disease, defined as at least one lesion that can be accurately measured in at least two dimensions Patients with measurable extraneural disease only are also eligible. * Phase II Age Patient must be 12 to \ • Inclusion Criteria
• 1 Uptake on \[68Ga\]Ga-DOTATATE PET Patients must have uptake on DOTATATE PET/CT in at least one tumor lesion (corresponding to known disease) equivalent to a Krenning score ≥2 (confirmed by central radiology review).
• 2 Prior Therapy Patients must have recovered from the acute treatment related toxicities (defined as ≤ grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy, radiotherapy, or any other treatment modality prior to entering this study.
• 3 Chemotherapy Patients must have received their last dose of known myelosuppressive anticancer therapy at least 21 days prior to enrollment or at least 42 days if nitrosourea.
• 4 Investigational/Biologic Agent ●Biologic or investigational agent (anti-neoplastic): Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the investigational or biologic agent ≥ 7 days prior to study enrollment. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. ●Monoclonal Antibodies and agents with known prolonged half-lives: Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the agent ≥ 28 days prior to study enrollment.
• 5 Radiation Patients must have had their last fraction of: * Craniospinal irradiation or total body irradiation or radiation to \> 50% of pelvis \> 3 months prior to enrollment. * Focal irradiation \> 4 weeks prior to enrollment
• 6 Stem Cell Transplant Patient must be: * ≥ 6 months since allogeneic stem cell transplant prior to enrollment with no evidence of active graft vs. host disease * ≥ 3 months since autologous stem cell transplant prior to enrollment
• 7 Growth Factors Patients must be off all colony-forming growth factor(s) for at least 1 week prior to enrollment (e.g. filgrastim, sargramostim or erythropoietin). Two weeks must have elapsed if patients received long-acting formulations.
• 8 Thrombopoietin receptor agonist * Phase I: Patients must be off thrombopoietin receptor agonists for at least 1 week prior to enrollment (e.g. romiplostim, eltrombopag) * Phase II: Patients can receive concurrent thrombopoietin receptor agonists
• 9 Somatostatin analogs Patients must be off long-acting somatostatin analogs for at least 4 weeks and off short-acting somastatin analogs (i.e., octreotide) for at least 24 hours.
• 10 Neurologic Status * Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment, documented by a detailed neurological exam. * Patients with seizure disorders may be enrolled if seizures are well controlled.
• 11 Performance Status Karnofsky Performance Scale (KPS for \> 16 years of age) or Lansky Performance Score (LPS for ≤ 16 years of age) assessed within two weeks of enrollment must be ≥ 50. Patients who are unable to walk because of neurologic deficits, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• 12 Organ Function Patients must have adequate organ and marrow function, for eligibility and enrollment, as defined below: * Adequate Bone Marrow Function as defined as: * Absolute neutrophil count ≥ 1.0 x 109 cells/ L * Platelets ≥100 x 109 cells/ L (unsupported, defined as no platelet transfusion within 7 days) * Hemoglobin ≥8 g/dl (may receive transfusions) * Adequate Renal Function as defined as: * Creatinine clearance or radioisotope GFR \>70mL/min/1.73m2 OR * A serum creatinine based on (Schwartz et al. J. Peds, 106:522, 1985) age/gender as follows: 1 to \< 2 years: maximum serum creatinine 0.6 mg/dL for males and females. 2 to \< 6 years: maximum serum creatinine 0.8 mg/dL for males and females. 6 to \< 10 years: maximum serum creatinine 1.0 mg/dL for males and females. 10 to \< 13 years: maximum serum creatinine 1.2 mg/dL for males and females. 13 to \< 16 years: maximum serum creatinine 1.5 mg/dL for males and 1.4 mg/dL for females. ≥ 16 years: maximum serum creatinine 1.7 mg/dL for males and 1.4 mg/dL for females. * Adequate Liver Function as defined as: * Total bilirubin ≤ 3 times institutional upper limit of normal (ULN) for age * AST(SGOT)/ALT(SGPT) ≤ 3 times institutional ULN * Serum albumin ≥ 2g/dL * Coagulation parameters: INR \<1.5 times ULN and aPTT \<1.5 times ULN unless patients are receiving therapeutic anticoagulation which affects these parameters * Adequate Cardiac Function as defined as: * Ejection fraction of ≥ 55% by echocardiogram * Serum electrolytes (Sodium, Potassium, Chloride) within institutional limits of normal (patients can be on enteral supplementation)
• 13 Corticosteroids Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment, with a maximum dexamethasone dose of 2.5mg/m2/day.
• 14 Pregnancy Status Female patients of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• 15 Pregnancy Prevention Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study and for at least 7 months after drug cessation in females of childbearing potential and for at least 4 months after drug cessation in males of child fathering potential.
• 16 Informed Consent The patient or parent/guardian is able to understand the consent and is willing to sign a written informed consent document according to institutional guidelines.
• Exclusion Criteria
• 1 Confirmed bone marrow metastatic disease Patients with confirmed metastatic disease to bone marrow are ineligible.
• 2 Presence of bulky disease Patients with bulky disease on imaging as described below are ineligible. Treating physicians are encouraged to request a rapid central imaging review to confirm fulfillment of these criteria if there are questions or concerns. Bulky disease is defined as: * Tumor with evidence of clinically significant uncal herniation or midline shift. * Tumor with diameter of \>5cm in one dimension on T2/FLAIR. * Tumor that in the opinion of the site investigator shows significant mass effect in either the brain or spine. Note that patients with metastatic or multi-focal disease (with exception of bone marrow) are eligible as long as no sites of disease meet above criteria for bulky disease.
• 3 Breast-feeding Nursing mothers are excluded from this study. There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Lutathera.
• 4 Concurrent Illness * Patients with a history of any other malignancy, except patients with a secondary brain tumor if the patient's prior malignancy has been in remission for at least 5 years from the end of treatment. * Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patient's ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results. * Patients with type I diabetes.
• 5 Concomitant Medications * Patients who are receiving any other anti-cancer or investigational drug therapy are ineligible. * Prior or current treatment with 177Lu-DOTATATE/TOC or 90Y-DOTATATE/TOC.
• 6 Prisoners will be excluded from this study.
• 7 Inability to participate: Patients who in the opinion of the investigator are unwilling or unable to return for required follow-up visits, obtain follow-up studies required to assess toxicity to therapy, or adhere to drug administration plan, other study procedures, and study restrictions.
• Inclusion of Women and Minorities Both males and females of all races and ethnic groups are eligible for this study.
• Screening Criteria
• 1 Diagnosis Patient must have a diagnosis of primary high-grade CNS tumor (any histopathologic diagnosis that is WHO grade III-IV) or meningioma (any histologic grade) that is recurrent, progressive, or refractory. Note that patients with DIPG (based on radiographic/clinical diagnosis) who have undergone biopsy will be eligible with histologic diagnosis of grade II-IV infiltrating glioma. All tumors must have histologic verification either at the time of diagnosis or recurrence, except for patients meningioma who have not previously undergone biopsy or resection. Note: Refractory disease is defined as the presence of persistent abnormality on conventional MRI that is further distinguished by histology (biopsy or sample of lesion) or advanced imaging, OR as determined by the treating physician and discussed with the primary investigator prior to enrollment.
• 2 Prior Therapy Patients must have recurred/progressed following prior standard therapy for their tumor. Note: Patients with meningioma, atypical meningioma, or anaplastic meningioma must have received at least surgical resection or radiation.
• 3 Screening Consent Participant/legal guardian is willing to sign a screening consent for \[68Ga\]Ga-DOTATATE PET imaging. The screening consent is to be obtained according to institutional guidelines. Assent, when appropriate, will be obtained according to institutional guidelines.
• Eligibility Criteria * Phase I Age Patient must be ≥ 4 and \<12 years of age at the time of enrollment. Disease Status: Patients who participate in the efficacy expansion cohort must have bi-dimensionally measurable disease, defined as at least one lesion that can be accurately measured in at least two dimensions Patients with measurable extraneural disease only are also eligible. * Phase II Age Patient must be 12 to \ • Inclusion Criteria
• 1 Uptake on \[68Ga\]Ga-DOTATATE PET Patients must have uptake on DOTATATE PET/CT in at least one tumor lesion (corresponding to known disease) equivalent to a Krenning score ≥2 (confirmed by central radiology review).
• 2 Prior Therapy Patients must have recovered from the acute treatment related toxicities (defined as ≤ grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy, radiotherapy, or any other treatment modality prior to entering this study.
• 3 Chemotherapy Patients must have received their last dose of known myelosuppressive anticancer therapy at least 21 days prior to enrollment or at least 42 days if nitrosourea.
• 4 Investigational/Biologic Agent ●Biologic or investigational agent (anti-neoplastic): Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the investigational or biologic agent ≥ 7 days prior to study enrollment. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. ●Monoclonal Antibodies and agents with known prolonged half-lives: Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the agent ≥ 28 days prior to study enrollment.
• 5 Radiation Patients must have had their last fraction of: * Craniospinal irradiation or total body irradiation or radiation to \> 50% of pelvis \> 3 months prior to enrollment. * Focal irradiation \> 4 weeks prior to enrollment
• 6 Stem Cell Transplant Patient must be: * ≥ 6 months since allogeneic stem cell transplant prior to enrollment with no evidence of active graft vs. host disease * ≥ 3 months since autologous stem cell transplant prior to enrollment
• 7 Growth Factors Patients must be off all colony-forming growth factor(s) for at least 1 week prior to enrollment (e.g. filgrastim, sargramostim or erythropoietin). Two weeks must have elapsed if patients received long-acting formulations.
• 8 Thrombopoietin receptor agonist * Phase I: Patients must be off thrombopoietin receptor agonists for at least 1 week prior to enrollment (e.g. romiplostim, eltrombopag) * Phase II: Patients can receive concurrent thrombopoietin receptor agonists
• 9 Somatostatin analogs Patients must be off long-acting somatostatin analogs for at least 4 weeks and off short-acting somastatin analogs (i.e., octreotide) for at least 24 hours.
• 10 Neurologic Status * Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment, documented by a detailed neurological exam. * Patients with seizure disorders may be enrolled if seizures are well controlled.
• 11 Performance Status Karnofsky Performance Scale (KPS for \> 16 years of age) or Lansky Performance Score (LPS for ≤ 16 years of age) assessed within two weeks of enrollment must be ≥ 50. Patients who are unable to walk because of neurologic deficits, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• 12 Organ Function Patients must have adequate organ and marrow function, for eligibility and enrollment, as defined below: * Adequate Bone Marrow Function as defined as: * Absolute neutrophil count ≥ 1.0 x 109 cells/ L * Platelets ≥100 x 109 cells/ L (unsupported, defined as no platelet transfusion within 7 days) * Hemoglobin ≥8 g/dl (may receive transfusions) * Adequate Renal Function as defined as: * Creatinine clearance or radioisotope GFR \>70mL/min/1.73m2 OR * A serum creatinine based on (Schwartz et al. J. Peds, 106:522, 1985) age/gender as follows: 1 to \< 2 years: maximum serum creatinine 0.6 mg/dL for males and females. 2 to \< 6 years: maximum serum creatinine 0.8 mg/dL for males and females. 6 to \< 10 years: maximum serum creatinine 1.0 mg/dL for males and females. 10 to \< 13 years: maximum serum creatinine 1.2 mg/dL for males and females. 13 to \< 16 years: maximum serum creatinine 1.5 mg/dL for males and 1.4 mg/dL for females. ≥ 16 years: maximum serum creatinine 1.7 mg/dL for males and 1.4 mg/dL for females. * Adequate Liver Function as defined as: * Total bilirubin ≤ 3 times institutional upper limit of normal (ULN) for age * AST(SGOT)/ALT(SGPT) ≤ 3 times institutional ULN * Serum albumin ≥ 2g/dL * Coagulation parameters: INR \<1.5 times ULN and aPTT \<1.5 times ULN unless patients are receiving therapeutic anticoagulation which affects these parameters * Adequate Cardiac Function as defined as: * Ejection fraction of ≥ 55% by echocardiogram * Serum electrolytes (Sodium, Potassium, Chloride) within institutional limits of normal (patients can be on enteral supplementation)
• 13 Corticosteroids Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment, with a maximum dexamethasone dose of 2.5mg/m2/day.
• 14 Pregnancy Status Female patients of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• 15 Pregnancy Prevention Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study and for at least 7 months after drug cessation in females of childbearing potential and for at least 4 months after drug cessation in males of child fathering potential.
• 16 Informed Consent The patient or parent/guardian is able to understand the consent and is willing to sign a written informed consent document according to institutional guidelines.
• Exclusion Criteria
• 1 Confirmed bone marrow metastatic disease Patients with confirmed metastatic disease to bone marrow are ineligible.
• 2 Presence of bulky disease Patients with bulky disease on imaging as described below are ineligible. Treating physicians are encouraged to request a rapid central imaging review to confirm fulfillment of these criteria if there are questions or concerns. Bulky disease is defined as: * Tumor with evidence of clinically significant uncal herniation or midline shift. * Tumor with diameter of \>5cm in one dimension on T2/FLAIR. * Tumor that in the opinion of the site investigator shows significant mass effect in either the brain or spine. Note that patients with metastatic or multi-focal disease (with exception of bone marrow) are eligible as long as no sites of disease meet above criteria for bulky disease.
• 3 Breast-feeding Nursing mothers are excluded from this study. There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Lutathera.
• 4 Concurrent Illness * Patients with a history of any other malignancy, except patients with a secondary brain tumor if the patient's prior malignancy has been in remission for at least 5 years from the end of treatment. * Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patient's ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results. * Patients with type I diabetes.
• 5 Concomitant Medications * Patients who are receiving any other anti-cancer or investigational drug therapy are ineligible. * Prior or current treatment with 177Lu-DOTATATE/TOC or 90Y-DOTATATE/TOC.
• 6 Prisoners will be excluded from this study.
• 7 Inability to participate: Patients who in the opinion of the investigator are unwilling or unable to return for required follow-up visits, obtain follow-up studies required to assess toxicity to therapy, or adhere to drug administration plan, other study procedures, and study restrictions.
• Inclusion of Women and Minorities Both males and females of all races and ethnic groups are eligible for this study.
DRUG: LUTATHERA® (Lutetium Lu 177 dotatate)
High Grade Glioma, Meningioma, Embryonal Tumor, Medulloblastoma, Anaplastic Ependymoma, Recurrent Diffuse Intrinsic Pontine Glioma, Recurrent Malignant Glioma, Recurrent Medulloblastoma, Recurrent Primary Central Nervous System Neoplasm, Refractory Diffuse Intrinsic Pontine Glioma, Refractory Malignant Glioma, Refractory Medulloblastoma, Refractory Primary Central Nervous System Neoplasm
Somatostatin Receptor, DOTATATE, Lutathera
Development and Validation of Patient Reported Outcome (PRO) Measures for Individuals With Neurofibromatosis 1 (NF1) and Plexiform Neurofibromas (pNFs)
cancer@cchmc.org
ALL
5 years and over
NCT02544022
* SUBJECT INCLUSION CRITERIA:
* Documented NF1 either by NIH clinical criteria or molecularly-proven mutation in the
NF1 gene, PER the Neurofibromatosis Diagnostic Criteria AND \>=1 plexiform neurofibroma in any location that is either symptomatic or asymptomatic, and is defined by the following:
• a neurofibroma that has grown along the length of a nerve and may involve multiple fascicles and branches OR a spinal neurofibroma that involves two or more levels with connection between the levels or extending laterally along the nerve OR a skin thickness neurofibroma;
• measures \>=3 cm on longest diameter by visual exam, palpation or 2D MR imaging OR \>=3 mL by volumetric MR imaging. * For phase 1, Age \>=5 years. (complete) * For phase 2, Age \>= 8 years * Ability of subject or parent or guardian to understand and the willingness to sign a written informed consent document. * Participants must be able to understand, read, and speak the English language. * For phase 1 focus groups only, patients need to report experiencing pNF related pain recently with a minimum pain level of 3 on the current NRS-11 or report taking prescription medication that reduces pain and experiencing pNF related pain recently with a minimum pain level of 1 on the current NRS-11. (complete) * For phase 2 patients with pain, patients need to report recently experiencing at least a minimal amount of pNF-related pain. Specifically, they will be asked if they recently experienced any pain in a target tumor area and will have to respond yes to be eligible. * For phase 2 patients without pain, patients need to report no recent pNF-related pain. Specifically, they will be asked if they recently experienced any pain in a target tumor area and will have to respond no to be eligible. PRIMARY CAREGIVER INCLUSION CRITERIA: * Primary caregiver (i.e. parent,guardian, grandparent) who is \>= 18 years old of participating subject \<= 17 years old * Participants must be able to understand, read, and speak the English language EXCLUSION CRITERIA: * Patients with severe cognitive or behavior impairments who, in the judgment of the investigators, would not be able to cooperate with the study procedures will be excluded. * Patients cannot be newly enrolled on a clinical trial to treat their pNF or cannot have started a new pain treatment regimen (e.g., medication, psychosocial therapy, physical therapy, etc.) at the time of enrollment. Specifically, patients will be ineligible if they were enrolled on a MEK inhibitor trial in the past 12 months or began a new pain medication or treatment within the past 3 months prior to enrollment on this study.
• a neurofibroma that has grown along the length of a nerve and may involve multiple fascicles and branches OR a spinal neurofibroma that involves two or more levels with connection between the levels or extending laterally along the nerve OR a skin thickness neurofibroma;
• measures \>=3 cm on longest diameter by visual exam, palpation or 2D MR imaging OR \>=3 mL by volumetric MR imaging. * For phase 1, Age \>=5 years. (complete) * For phase 2, Age \>= 8 years * Ability of subject or parent or guardian to understand and the willingness to sign a written informed consent document. * Participants must be able to understand, read, and speak the English language. * For phase 1 focus groups only, patients need to report experiencing pNF related pain recently with a minimum pain level of 3 on the current NRS-11 or report taking prescription medication that reduces pain and experiencing pNF related pain recently with a minimum pain level of 1 on the current NRS-11. (complete) * For phase 2 patients with pain, patients need to report recently experiencing at least a minimal amount of pNF-related pain. Specifically, they will be asked if they recently experienced any pain in a target tumor area and will have to respond yes to be eligible. * For phase 2 patients without pain, patients need to report no recent pNF-related pain. Specifically, they will be asked if they recently experienced any pain in a target tumor area and will have to respond no to be eligible. PRIMARY CAREGIVER INCLUSION CRITERIA: * Primary caregiver (i.e. parent,guardian, grandparent) who is \>= 18 years old of participating subject \<= 17 years old * Participants must be able to understand, read, and speak the English language EXCLUSION CRITERIA: * Patients with severe cognitive or behavior impairments who, in the judgment of the investigators, would not be able to cooperate with the study procedures will be excluded. * Patients cannot be newly enrolled on a clinical trial to treat their pNF or cannot have started a new pain treatment regimen (e.g., medication, psychosocial therapy, physical therapy, etc.) at the time of enrollment. Specifically, patients will be ineligible if they were enrolled on a MEK inhibitor trial in the past 12 months or began a new pain medication or treatment within the past 3 months prior to enrollment on this study.
Neurofibromatosis 1, Plexiform Neurofibromas
Pain Scale, QOL, Tool Validation, Cognitive Interviews, Natural History
A Study of Selinexor in People With Wilms Tumors and Other Solid Tumors
- cancer@cchmc.org
ALL
1 year and over
PHASE2
NCT05985161
Inclusion Criteria:
* Age:
• Age ≥ 6 at the time of informed consent
• Age ≥ 2 years to \< 6 years at time of informed consent (Refer to Section 4.3): If PK cohort 1 is open, patients in this age range may enroll onto this cohort. If PK cohort 1 has been completed and deemed sufficient to proceed, then such patients may enroll onto the phase 2.
• Age ≥ 12 months to \< 2 years at time of informed consent (Refer to Section 4.3): If PK cohort 2 is open, patients in this age range may enroll onto this cohort. If PK cohort 2 has been completed and deemed sufficient to proceed, then such patients may enroll onto the phase 2. * Consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines. * Performance: Karnofsky ≥ 60% for patients \> 16 years of age and Lansky ≥ 60 for patients ≤ 16 years of age. * Diagnosis: Patients must enroll into one of the following cohorts:
• Cohort A: Any type of Wilms tumor or nephroblastoma is eligible for this study provided they meet at least one of these criteria: (1) in their second or greater relapse, (2) refractory or in their first relapse with high risk histology (i.e., any anaplastic or blastemal-type after neoadjuvant chemotherapy), or (3) refractory or in first relapse without high risk histology but after having received chemotherapies other than the initial 4 agents used as current standard of care in the up-front setting for non-high risk cases - specifically vincristine, dactinomycin, doxorubicin, and irinotecan (i.e., any patient who relapses following an initial regimen more intense than EE4A, DD4A, VAD, AVD, or VIVA; for example, those including cyclophosphamide/etoposide - such as Regimen I, M, or MVI - or those additionally including carboplatin - such as Regimens UH-1, UH-2, or UH-3).
• Cohort B: Any Rhabdoid tumor is eligible for this cohort. This includes, but is not limited to, related subtypes of rhabdoid tumors such as atypical teratoid rhabdoid tumors (ATRT), malignant rhabdoid tumors of the kidney (MRTK), malignant rhabdoid tumors of the soft tissue and liver, small cell undifferentiated hepatoblastomas (SCUH), and small-cell carcinoma of the ovary of hypercalcemic type (SCCOHT). Patients must have failed to respond to at least 1 line of systemic therapy prior to enrollment.
• Cohort C: Patients with progressive, relapsed, unresectable or metastatic MPNST, are eligible for this cohort. Patients must have failed to respond to at least 1 line of systemic therapy prior to enrollment.
• Cohort D: Patients must not qualify for Cohorts A, B, or C but have a solid tumor (no hematologic malignancies including lymphoma) for which there is specific evidence that this particular patient's tumor may benefit from selinexor. Patients must have failed to respond to at least 1 line of systemic therapy prior to enrollment. Examples of evidence are listed below. All patients in this cohort require approval of study principal investigator and must provide documentation of specific supporting evidence. i. Tumor XPO1 Dependency: Defined as either Darwin OncoTarget demonstrating XPO1 as aberrantly activated or Darwin OncoTreat demonstrating context-specific tumor checkpoint inversion with Selinexor, both of which must be significant at a -log10 (Bonferroni corrected p-value) of 5 or greater. ii. Tumor XPO1 Activation: Defined as the detection of a gain of function mutation in XPO1, specifically E571K. Additionally, detection of elevated transcriptomic or proteomic expression of XPO1 in the tumor via RNAseq or IHC, respectively, would be considered sufficient for treatment. iii. Preclinical Tumor Testing: Defined as testing of Selinexor on patient derived cell line, organoid, or xenograft models of the patient's tumor (or other related tumors) performed in a laboratory context and for which, in the investigator's opinion, demonstrates promising activity. Testing may include commercial testing as well as academic laboratory testing. * Cohort E: Patients must have a solid tumor with an activating genomic alteration (e.g. fusion or internal tandem duplication) involving BCOR. Specific examples of qualifying alterations including BCOR-ITD, BCOR-CCNB3, BCOR-MAML3 and ZC3H7B-BCOR; Other potentially qualifying BCOR alterations require approval of study principal investigator; note that loss of function alterations of BCOR would not qualify. * Disease Status: Patients on the phase II portion of the study must have measurable disease whereas patients on the PK cohorts can have either evaluable or measurable disease as measured by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (Version 1.1). a. Primary Brain Tumors: Patients with primary brain tumors are eligible and must also have measurable disease for the phase II (as well as evaluable or measurable for the PK cohorts), but this can be defined as at least equal or greater than twice the slice thickness in two perpendicular diameters on MRI OR diffuse leptomeningeal disease OR clear MRI evidence of disease that may not be measurable in two perpendicular diameters OR positive CSF cytology alone. * Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and meet minimum washout durations (shown below) from prior therapy.
• Anti-cancer agents not known to be myelosuppressive: ≥ 7 days
• Anti-cancer and cytotoxic agents known to be myelosuppressive: ≥ 21 days
• Immunotherapies (including antibodies, interleukins, interferons, etc.): ≥ 21 days
• Adoptive cellular therapies (including modified T cells, vaccines, etc.): ≥ 42 days
• Autologous stem cell infusion (boost, no conditioning): ≥ 21 days
• Autologous stem cell transplantation (with conditioning): ≥ 42 days
• Allogeneic bone marrow transplantation: ≥ 84 days
• Focal external beam radiation (e.g., limited sites of disease): ≥ 14 days
• Substantial external beam radiation (e.g. whole lung or abdomen): ≥ 42 days
• Radiopharmaceutical therapy (e.g., radiolabeled antibody or MIBG): ≥ 42 days * Hepatic Function: Adequate function (within 14 days prior to C1D1), defined as:
• Total bilirubin \< 1.5 × upper limit of normal (ULN) (except patients with Gilbert's syndrome, who must have a total bilirubin of \<3 × ULN)
• Alanine aminotransferase (ALT) \< 3 × ULN
• Serum albumin ≥ 2 g/dL * Renal Function: Adequate function (within 14 days prior to C1D1) defined as a GFR ≥ 50 ml/min/1.73 m2 determined via any of these methods:
• Nuclear radioisotope
• 24 hr urine creatinine clearance
• Serum cystatin c
• Serum creatinine using the Schwartz formula for estimating creatinine clearance (Schwartz et al. J Peds, 106:522, 1985) * Hematologic Function: Adequate function (within 14 days prior to C1D1), defined as:
• Absolute neutrophil count (ANC) ≥ 1000/mm3
• Platelet count ≥ 100,000/mm3
• Note: patients may not receive platelet transfusions nor hematopoietic growth factor support, including granulocyte-colony stimulating factor (e.g. filgrastim) and platelet stimulators (e.g. romiplostim) for at least 7 days prior to demonstrating adequate hematologic function.
Exclusion Criteria:
* Prior Therapy: Has received selinexor or another XPO1 inhibitor previously.
* Infection: Patients who have an uncontrolled infection are not eligible. Patients on prophylactic antibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable
* Transplants: Patients who have received allogeneic bone marrow transplant are potentially eligible unless they are being actively treated for GvHD. Patients who have had a prior solid organ transplantation are not eligible.
* Compliance: Patients who as a result of serious medical, psychiatric, and/or social situation(s), in the opinion of the investigator, may not be able to comply with supportive care, safety monitoring, or any other key requirements of the study protocols are not eligible.
* Pregnancy and Breast-feeding: Pregnant or breast-feeding women will not be entered on this study because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal.
* Contraception: Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control. DRUG: Selinexor
Wilms Tumor, Rhabdoid Tumor, Malignant Peripheral Nerve Sheath Tumors, MPNST, Nephroblastoma, XPO1 Gene Mutation, Solid Tumor
Wilms Tumor, Rhabdoid Tumor, Malignant Peripheral Nerve Sheath Tumors, MPNST, Nephroblastoma, XPO1, Selinexor, Memorial Sloan Kettering Cancer Center, 22-393, Solid Tumor
Tegavivint for the Treatment of Recurrent or Refractory Solid Tumors, Including Lymphomas and Desmoid Tumors
- cancer@cchmc.org
ALL
12 months to 30 years old
PHASE1
NCT04851119
Inclusion Criteria:
* PART A: Patients must be \>= 12 months and =\< 21 years of age at the time of study enrollment
* PART B: Patients must be \>= 12 months and =\< 30 years of age at the time of study enrollment
* Patients with recurrent or refractory solid tumors including non-Hodgkin lymphoma and desmoid tumors are eligible. Patients must have had histologic verification of malignancy at original diagnosis or relapse
* PART A: Patients with relapsed or refractory solid tumors, including patients with non-Hodgkin lymphoma and desmoid tumors
* PART B: Patients with recurrent or refractory Ewing sarcoma, desmoid tumors, osteosarcoma, liver tumors (HCC and hepatoblastoma), Wilms tumor, and tumors with Wnt pathway aberrations. For the Wnt pathway aberrations cohort we will include the most common CTNNB1 mutations (S37F, S45F, T41A, S45P, S33C, S37C, D32Y, S33F, T41I, G34R, G34V, D32N, S33P, G34E, D32G) as well as any loss of function mutations in the APC, Axin2FBXW7, TCF7L2, and RNF43 genes or any gain-of-function mutations in the GSK3B, LRP6, and LGR5 genes. For patients without prior sequencing, immunohistochemistry (IHC), is required. IHC showing strong nuclear beta-catenin staining will be accepted for the following tumor types: colorectal carcinoma, melanoma, endometrial cancer, ovarian cancer, neuroblastoma, non-Hodgkin lymphoma, pancreatic ductal adenocarcinoma, and solid pseudopapillary tumor of the pancreas
* PART A: Patients must have either measurable or evaluable disease. For desmoid tumors, the patient must have disease that the investigator deems unresectable or sufficiently morbid or potentially life-threatening that there is favorable risk/benefit to the patient to participate in the trial
* PART B: Patients must have measurable disease. For desmoid tumors, the patient must have measurable disease that the investigator deems unresectable or sufficiently morbid or potentially life-threatening that there is favorable risk/benefit to the patient to participate in the trial
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately.
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
* Solid tumor patients: \>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
* Non-Hodgkin lymphoma patients
* A waiting period prior to enrollment is not required for patients receiving standard maintenance chemotherapy (i.e., corticosteroid, vincristine, thioguanine \[6MP\], and/or methotrexate)
* \>= 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy
* NOTE: Cytoreduction with hydroxyurea must be discontinued \>= 24 hours prior to the start of protocol therapy
* Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil counts \[ANC\]): \>= 7 days after the last dose of agent
* Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1
* Corticosteroids: If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
* Stem cell Infusions (with or without total-body irradiation \[TBI\]):
* Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: \>= 84 days after infusion and no evidence of graft versus host disease (GVHD)
* Autologous stem cell infusion including boost infusion: \>= 42 days.
* Cellular therapy: \>= 42 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.).
* External beam radiation therapy (XRT)/external beam irradiation including protons: \>= 14 days after local XRT; \>= 150 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow (BM) radiation
* Radiopharmaceutical therapy (e.g., radiolabeled antibody, iobenguane I-131 \[131I MIBG\]): \>= 42 days after systemically administered radiopharmaceutical therapy
* Patients must not have received prior exposure to tegavivint
* PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Peripheral absolute neutrophil count (ANC) \>= 1000/uL (within 7 days prior to enrollment)
* PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (within 7 days prior to enrollment)
* PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Hemoglobin \>= 8.0 g/dL at baseline (may receive red blood cell \[RBC\] transfusions) (within 7 days prior to enrollment)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled on Part A must be evaluable for hematologic toxicity
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a creatinine based on age/gender as follows (within 7 days prior to enrollment):
* Age; maximum serum creatinine
* Age 1 to \< 2 years; 0.6 mg/dL (male); 0.6 mg/dL (female)
* Age 2 to \< 6 years; 0.8 mg/dL (male); 0.8 mg/dL (female)
* Age 6 to \< 10 years; 1 mg/dL (male); 1 mg/dL (female)
* Age 10 to \< 13 years; 1.2 mg/dL (male); 1.2 mg/dL (female)
* Age 13 to \< 16 years; 1.5 mg/dL (male); 1.4 mg/dL (female)
* Age \>= 16 years; 1.7 mg/dL (male); 1.4 mg/dL (female)
* PATIENTS WITH SOLID TUMORS: Bilirubin (sum of conjugated + unconjugated or total) =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
* PATIENTS WITH SOLID TUMORS: Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L (within 7 days prior to enrollment)
* PATIENTS WITH SOLID TUMORS: Albumin \>= 2 g/dL (within 7 days prior to enrollment)
Exclusion Criteria:
* Pregnant or breast-feeding women will not be entered on this study because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control
* Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Patients who are currently receiving another investigational drug are not eligible
* Patients who are currently receiving other anti-cancer agents are not eligible
* Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
* Patients who are currently receiving drugs that are strong inducers or inhibitors of CYP3A4 are not eligible. Strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to the 1st dose of tegavivint to the end of the study
* Patients who have received bisphosphonates within 4 weeks prior to study enrollment will be excluded
* Patients who have received denosumab within 180 days prior to study enrollment will be excluded
* Patients with primary brain tumors are ineligible
* Patients with known central nervous system (CNS) metastasis, except for craniopharyngeal tumors, will be excluded
* Patients with a known metabolic bone disease (ex: hyperparathyroidism, Paget's disease, osteomalacia) are not eligible
* Patients with a disorder associated with abnormal bone metabolism will be excluded
* Patients with grade \>= 2 hypocalcemia that is not corrected with oral calcium supplementation will be excluded
* Patients with vitamin D \< 20 ng/mL will require supplementation, or will otherwise be excluded. Patients must agree to take vitamin D +/- calcium supplements (if necessary) according to institutional or published guidelines. Additional calcium supplementation is not required if adequate dietary intake can be ascertained
* Patients with pre-existing grade 3 osteoporosis are excluded
* Patients who have an uncontrolled infection are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible PROCEDURE: Biospecimen Collection, PROCEDURE: Dual X-ray Absorptiometry, DRUG: Tegavivint, PROCEDURE: X-Ray Imaging
Colorectal Carcinoma, Endometrial Carcinoma, Melanoma, Neuroblastoma, Ovarian Carcinoma, Pancreatic Ductal Adenocarcinoma, Recurrent Desmoid Fibromatosis, Recurrent Ewing Sarcoma, Recurrent Hepatoblastoma, Recurrent Hepatocellular Carcinoma, Recurrent Malignant Solid Neoplasm, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Refractory Desmoid Fibromatosis, Refractory Ewing Sarcoma, Refractory Hepatoblastoma, Refractory Hepatocellular Carcinoma, Refractory Malignant Solid Neoplasm, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Solid Pseudopapillary Neoplasm of the Pancreas, Wilms Tumor
Identification of Biomarkers for Patients with Vascular Anomalies
- hvmcresearch@cchmc.org
ALL
Not specified
NCT03001180
Inclusion Criteria:
* Any patient having labs drawn as standard of care will have blood drawn for the study if consented/ assented.
* All patients who are undergoing a surgical procedure or sclerotherapy are currently consented for participation in the tissue bank.
Exclusion Criteria:
* N/A Vascular Anomaly, Generalized Lymphatic Anomaly, Kaposiform Hemangioendothelioma, Kaposiform Lymphangiomatosis, Gorham-Stout Disease, Klippel Trenaunay Syndrome, Congenital Lipomatous Overgrowth, Vascular Malformations, and Epidermal Nevi
Generalized Lymphatic Anomaly, Vascular Anomaly, Kaposiform Hemangioendothelioma, Kaposiform Lymphangiomatosis, Vascular Endothelial Growth Factor, Biomarkers, GLA, KLA, KHE, GSD
Active Surveillance, Bleomycin, Etoposide, Carboplatin or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors
- cancer@cchmc.org
ALL
PHASE3
NCT03067181
Inclusion Criteria:
* There is no age limit for the low risk stratum (stage I ovarian immature teratoma and stage I non-seminoma or seminoma malignant GCT \[all sites\])
* Standard risk 1: Patients must be \< 11 years of age at enrollment
* Standard risk 2: Patients must be \>= 11 and \< 25 years of age at enrollment
* Patients enrolling on one of the low risk arms must be newly diagnosed with a stage I germ cell tumor; for the standard risk arms, patients must be newly diagnosed with malignant germ cell tumor (stage II or higher).
* Histologic confirmation of a primary extracranial germ cell tumor in any of the categories outlined below is required of all patients at enrollment , with the following exceptions:
* Among patients were initially diagnosed with completely resected non-seminoma malignant GCT and later recur during observation post surgery, a diagnostic biopsy is not required for enrollment if elevated tumor markers rise to \> 5 x upper limit of normal (ULN) on at least 2 measurements taken at least 1 week apart. The pathology report of initial surgery should be provided
* Patients may be enrolled without histologic or cytologic confirmation in the rare case where there are exceptionally raised tumor markers (alpha fetoprotein \[AFP- ≥ 500 ng/mL or HCG ≥ 500 IU/L) and radiologic features consistent with GCT. In addition, the treating clinician must deem that the patient's tumor is not suitable for upfront resection and that a biopsy is not in the patient's best interest; or that there is a need to start therapy urgently
* Low risk immature teratoma (IT); site: ovarian; stage: any; grade: any; histology: pure immature teratoma, mixed immature and mature teratoma, (may contain microscopic foci of yolk sac tumor \[\< 3 mm\], but no other pathological evidence of MGCT); tumor markers: alpha-FP =\< 1,000 ng/mL, beta-HCG institutional normal; all ages
* Low risk stage I non-seminoma MGCT; site: ovarian, testicular, or extragonadal; stage: COG stage I, FIGO stage IA and IB, American Joint Committee on Cancer (AJCC) testicular stage IA, IB and IS; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or mixed); all ages
* Low risk stage I seminoma-MGCT; site: testicular; stage: COG stage I; AJCC testicular stage IA IB, and IS; histology: must contain only seminoma; may contain immature/mature teratoma; may NOT contain yolk sac tumor, embryonal carcinoma, or choriocarcinoma; all ages
* Standard risk 1 (SR1); site: ovarian, testicular, or extragonadal; stage: COG stage II-IV, FIGO stage IC-IV, (International Germ Cell Consensus Classification \[IGCCC\] criteria DO NOT apply); histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) \< 11
* Standard risk 2 (SR2)
* Site: ovarian; stage: COG stage II, III, and III-X, FIGO stage IC, II and III; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) \>= 11 and \< 25
* Site: testicular; stage: COG stage II-IV, AJCC stage II, III, IGCCC good risk; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma: must be IGCCC good risk; post op: alpha-FP \< 1,000 ng/mL, beta-HCG \< 5,000 IU/mL and lactate dehydrogenase (LDH) \< 3.0 x normal; age (years) \>= 11 and \< 25
* Notes:
* IGCCC criteria only apply to SR2 patients with a testicular primary tumor
* Use post-op tumor marker levels to determine IGCCC risk group
* Pure seminoma patients are not eligible for the standard risk arms of the study
* For the low risk stage I non-seminoma MGCT and the standard risk arms, components of yolk sac tumor, embryonal carcinoma, or choriocarcinoma can be mixed with other forms of GCT, such as seminoma or mature or immature teratoma; if yolk sac tumor is the only malignant component present, then it must be deemed by the pathologist to be greater than a "microscopic component" of yolk sac tumor
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, 2 or 3; use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* Organ function requirements apply ONLY to patients who will receive chemotherapy (SR1 and SR2 patients)
* Adequate renal function defined as:
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 (within 7 days prior to enrollment) OR
* A serum creatinine based on age/sex as follows (within 7 days prior to enrollment): (mg/dL)
* 1 month to \< 6 months male: 0.4 female: 0.4
* 6 months to \< 1 year male: 0.5 female: 0.5
* 1 to \< 2 years male: 0.6 female: 0.6
* 2 to \< 6 years male: 0.8 female: 0.8
* 6 to \< 10 years male: 1 female: 1
* 10 to \< 13 years male: 1.2 female: 1.2
* 13 to \< 16 years: male: 1.5 female: 1.4
* \>= 16 years male: 1.7 female: 1.4
* Total bilirubin =\< 2 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
* Unless due to Gilbert's disease, malignant involvement of liver or vanishing bile duct syndrome
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 x upper limit of normal (ULN) (within 7 days prior to enrollment)
* Unless due to Gilbert's disease, malignant involvement of liver or vanishing bile duct syndrome
* Peripheral absolute neutrophil count (ANC) \>= 750/mm\^3 (within 7 days prior to enrollment) AND
* Platelet count \>= 75,000/mm\^3 (within 7 days prior to enrollment)
* Patients enrolling on the standard risk arms must be medically fit to receive protocol treatment and with no contraindications to protocol treatment
* Eligibility criteria to participate in the pilot study of the AYA-Hears instrument (patient reported outcomes \[PROs\] of ototoxicity) Note: participants in group 1 will not receive AGCT1531 protocol-directed therapy; all other AYA-HEARS patients must be enrolled on the AGCT1531 SR2 arm in order to participate
* \>= 11 and \< 25 years old at enrollment
* Able to fluently speak and read English
* Has received prior cisplatin- or carboplatin-based chemotherapy regimen for malignancy including diagnoses other than germ cell tumor
* Followed for cancer or survivorship care at one of the following institutions:
* Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
* Dana Farber/Harvard Cancer Center
* Hospital for Sick Children
* Children's Hospital of Eastern Ontario
* Oregon Health and Science University
* Seattle Children's Hospital
* Yale University
Exclusion Criteria:
* Patients with any diagnoses not listed including:
* Stage I testicular cancer patients who have undergone primary RPLND (retroperitoneal lymph node dissection)
* Pure ovarian or extragonadal dysgerminoma/seminoma
* Pure mature teratoma
* Pure immature teratoma with alpha-fetoprotein (AFP) \>= 1000 ng/mL
* "Poor risk" GCT (age \>= 11 years old and COG stage IV ovarian, COG stage II- IV extragonadal, or IGCCC intermediate or poor risk testicular), or
* Primary central nervous system (CNS) germ cell tumor
* Germ cell tumor with somatic malignant transformation
* Spermatocytic seminoma
* Patients must have had no prior systemic therapy for the current cancer diagnosis
* Patients must have had no prior radiation therapy with the exception of CNS irradiation of brain metastases; (this exception only applies to SR1 patients; any patients over age 11 with distant metastases to brain \[stage IV disease\] would be considered poor risk and therefore not eligible for this trial)
* Patients with significant, pre-existing co-morbid respiratory disease that contraindicate the use of bleomycin are ineligible for the standard risk arms of the trial
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential; (this criteria applies ONLY to patients who will receive chemotherapy \[SR1 and SR2 patients\])
* Lactating females who plan to breastfeed their infants; (this criteria applies ONLY to patients who will receive chemotherapy \[SR1 and SR2 patients\])
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation; (this criteria applies ONLY to patients who will receive chemotherapy \[SR1 and SR2 patients\]) OTHER: Best Practice, PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, BIOLOGICAL: Bleomycin Sulfate, DRUG: Carboplatin, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Etoposide, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Pulmonary Function Test, OTHER: Questionnaire Administration
Childhood Extracranial Germ Cell Tumor, Extragonadal Embryonal Carcinoma, Germ Cell Tumor, Malignant Germ Cell Tumor, Malignant Ovarian Teratoma, Stage I Ovarian Choriocarcinoma, Stage I Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage I Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage I Testicular Choriocarcinoma AJCC v6 and v7, Stage I Testicular Embryonal Carcinoma AJCC v6 and v7, Stage I Testicular Seminoma AJCC v6 and v7, Stage I Testicular Yolk Sac Tumor AJCC v6 and v7, Stage II Ovarian Choriocarcinoma, Stage II Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage II Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage II Testicular Choriocarcinoma AJCC v6 and v7, Stage II Testicular Embryonal Carcinoma AJCC v6 and v7, Stage II Testicular Yolk Sac Tumor AJCC v6 and v7, Stage III Ovarian Choriocarcinoma, Stage III Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage III Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage III Testicular Choriocarcinoma AJCC v6 and v7, Stage III Testicular Embryonal Carcinoma AJCC v6 and v7, Stage III Testicular Yolk Sac Tumor AJCC v6 and v7, Stage IV Ovarian Choriocarcinoma, Stage IV Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage IV Ovarian Yolk Sac Tumor AJCC v6 and v7, Testicular Mixed Choriocarcinoma and Embryonal Carcinoma, Testicular Mixed Choriocarcinoma and Teratoma, Testicular Mixed Choriocarcinoma and Yolk Sac Tumor
Project: Every Child for Younger Patients With Cancer
- cancer@cchmc.org
ALL
Up to 25 years old
NCT02402244
Inclusion Criteria:
* Enrollment must occur within 6 months of initial disease presentation OR within 6 months of refractory disease, disease progression, disease recurrence, second or secondary malignancy, or post-mortem
* Patients previously enrolled on ACCRN07 are eligible to enroll on Tracking Outcome, Registry and Future Contact components of APEC14B1 any time after they reach age of majority
* Patients with a known or suspected neoplasm that occurs in the pediatric, adolescent or young adult populations are eligible for enrollment as follows:
* All cancer cases with an International Classification of Diseases for Oncology (ICD-O) histologic behavior code of one "1" (borderline), two "2" (carcinoma in situ) or three "3" (malignant)
* All neoplastic lesions of the central nervous system regardless of behavior, i.e., benign, borderline or malignant
* All neoplastic lesions of the kidney regardless of behavior, i.e., benign, borderline or malignant
* The following other benign/borderline conditions:
* Mesoblastic nephroma
* Teratomas (mature and immature types)
* Myeloproliferative diseases including transient myeloproliferative disease
* Langerhans cell histiocytosis
* Lymphoproliferative diseases
* Desmoid tumors
* Gonadal stromal cell tumors
* Neuroendocrine tumors including pheochromocytoma
* Melanocytic tumors, except clearly benign nevi
* Ganglioneuromas
* Subjects must be =\< 25 years of age at time of original diagnosis, except for patients who are being screened specifically for eligibility onto a COG (or COG participating National Clinical Trials Network \[NCTN\]) therapeutic study, for which there is a higher upper age limit
* All patients or their parents or legally authorized representatives must sign a written informed consent and agree to participate in at least one component of the study; parents will be asked to sign a separate consent for their own biospecimen submission
* If patients or their parents or legally authorized representatives have not signed the Part A subject consent form at the time of a diagnostic bone marrow procedure, it is recommended that they initially provide consent for drawing extra bone marrow using the Consent for Collection of Additional Bone Marrow; consent using the Part A subject consent form must be provided prior to any other procedures for eligibility screening or banking under APEC14B1 OTHER: Cytology Specimen Collection Procedure, OTHER: Medical Chart Review
Adrenal Gland Pheochromocytoma, Carcinoma In Situ, Central Nervous System Neoplasm, Childhood Immature Teratoma, Childhood Kidney Neoplasm, Childhood Langerhans Cell Histiocytosis, Childhood Mature Teratoma, Congenital Mesoblastic Nephroma, Desmoid Fibromatosis, Ganglioneuroma, Lymphoproliferative Disorder, Malignant Neoplasm, Malignant Solid Neoplasm, Melanocytic Neoplasm, Myeloproliferative Neoplasm, Neoplasm of Uncertain Malignant Potential, Neuroendocrine Neoplasm, Stromal Neoplasm
Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial
- cancer@cchmc.org
ALL
PHASE2
NCT05564377
Inclusion Criteria:
* Patient must have measurable disease
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status between 0-2 OR patient must have Lansky performance status of \>= 50% or Karnofsky performance status of \>= 50%
* Patient must be deemed potentially eligible for a ComboMATCH Treatment Trial as assessed by the enrolling provider
* All patients must have sequencing results available from a National Cancer Institute (NCI) credentialed Designated Laboratory (DL)
* Patients must have locally advanced or advanced histologically documented solid tumors requiring therapy and meet one of the following criteria:
* Patients must have progressed on at least one line of standard systemic therapy OR
* Patients whose disease has no standard treatment that has been shown to prolong overall survival
* Patient must meet one of the following requirements:
* Patients 18 years and older who have tumor amenable to minimal risk image-guided or direct vision biopsy and must be willing and able to undergo a tumor biopsy to obtain samples for research if the patient is to enroll in a ComboMATCH treatment trial OR
* Patients 18 years and older who do not have disease that is biopsiable at minimal risk to the patient must confirm availability of an archival tumor tissue specimen for submission for research if the patient enrolls to a ComboMATCH Treatment Trial. This tumor tissue must meet the following criteria:
* Tissue must have been collected within 12 months prior to registration to the EAY191 Registration Trial
* Patient must not have had a Response Evaluation Criteria in Solid Tumors (RECIST) response (complete response \[CR\] or partial response \[PR\]) to any intervening therapy after collection of the tissue
* Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be available OR
* Patients under 18 years old must confirm availability of an archival tumor tissue specimen for submission for research if patient enrolls to a ComboMATCH Treatment Trial. This tumor tissue must meet the following criteria:
* Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be available
* NOTE: See specific ComboMATCH Treatment Trial protocol for tissue collection and management instructions. Performance of the mandatory research biopsy or submission of pre-trial formalin-fixed paraffin-embedded (FFPE) and collection and submission of the blood specimens for the integrated studies will be performed under the consent authority of the specific treatment trial protocol to which the patient is registered. No procedures to collect specimens for research only are to be performed for patients registered to the EAY191 Registration Trial only
* NOTE: Each ComboMATCH Treatment Trial contains specific eligibility criteria. If patient is found to not be eligible for the assigned ComboMATCH Treatment Trial, indication of ineligibility will trigger re-evaluation and potential assignment to another Treatment Trial DRUG: Alpelisib, DRUG: Binimetinib, PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography Test, DRUG: Fluorouracil, DRUG: Fulvestrant, DRUG: Ipatasertib, DRUG: Leucovorin, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Multigated Acquisition Scan, PROCEDURE: Mutation Carrier Screening, DRUG: Neratinib Maleate, DRUG: Nilotinib Hydrochloride Monohydrate, DRUG: Olaparib, DRUG: Oxaliplatin, DRUG: Paclitaxel, DRUG: Palbociclib, BIOLOGICAL: Panitumumab, PROCEDURE: Positron Emission Tomography, DRUG: Selumetinib Sulfate, DRUG: Sotorasib
Advanced Malignant Solid Neoplasm, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Locally Advanced Malignant Solid Neoplasm, Malignant Female Reproductive System Neoplasm, Metastatic HER2-Negative Breast Carcinoma, Metastatic Malignant Solid Neoplasm, Recurrent Endometrial Carcinoma, Recurrent Fallopian Tube Carcinoma, Recurrent Malignant Female Reproductive System Neoplasm, Recurrent Malignant Solid Neoplasm, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma, Unresectable HER2-Negative Breast Carcinoma, Unresectable Malignant Solid Neoplasm
Studying Health Outcomes After Treatment in Patients With Retinoblastoma (RIVERBOAT)
Amanda Pfeiffer - amanda.pfeiffer@cchmc.org
ALL
NCT03932786
* Unilateral or bilateral intraocular retinoblastoma
* Diagnosis between the ages of 0 - 17.99 years
* Diagnosis on or after January 1, 2008
* No exclusions based on primary or secondary treatment modalities
* Retrospective group patients must be ≥ 6 months post end of treatment at study entry
* For those already at this timepoint, they are now eligible
* For those in treatment, or otherwise not yet at this timepoint, they are eligible once at they are ≥ 6 months post end of treatment
* Prospective group patients must not have begun treatment
* Patients with diminished capacity will not be enrolled.
* Language: Patients must be able to communicate in English, French, or Spanish
* Sibling Cohort: One sibling, not affected by retinoblastoma will be enrolled, preference for the sibling closest in age to the RB patient.
* Regulatory Requirements: All patients and/or their parents or legal guardians must sign a written informed consent. All institutional, FDA, and NCI requirements for human studies must be met.
PROCEDURE: Biospecimen collection, OTHER: Vision assessment, OTHER: Questionnaire administration, OTHER: Quality of life assessment, OTHER: Laboratory Biomarker Analysis
Retinoblastoma, Cancer Survivor, Biological Sibling, Intraocular Retinoblastoma, Unilateral Retinoblastoma
64Cu-LNTH-1363S in Patients With Sarcoma or Gastrointestinal Tract Cancer (PHANTOM)
- cancer@cchmc.org
ALL
15 years and over
PHASE1
NCT06298916
Inclusion Criteria:
Part 1
Patients are eligible to be included in the study only if all of the following criteria apply:
• Patient must be ≥ 15 years of age and must have provided written informed consent and assent, where applicable (by patient or legal guardian). Those aged ≥15 to \<18 years must weigh at least 55 kg.
• Patients with suspected FAP-expressing metastatic sarcoma.
• Patients must have histological, pathological, and/or cytological confirmation of a metastatic sarcoma (e.g., undifferentiated pleomorphic sarcoma, liposarcoma, Leiomyosarcoma, myxofibrosarcoma, solitary fibrous tumor, Ewing's sarcoma, synovial sarcoma, sarcoma not otherwise specified, osteosarcoma).
• Patients must be willing to consent to provide sufficient and adequate archived tumor tissue samples (formalin fixed, paraffin embedded sample), preferably from a biopsy of a tumor lesion obtained either at the time of or after the diagnosis of disease; if archival tissue sample is unavailable, a new biopsy should be performed on the most accessible lesion(s) to obtain the tumor tissue sample.
• Adequate renal function as determined by a calculated creatinine clearance ≥ 60 mL/min (Cockcroft Gault equation).
• Women of childbearing potential (WOCBP) must have a negative beta-human chorionic gonadotropin (β-hCG) test and must not be breastfeeding. WOCBP must agree to use a highly effective method of contraception during the study and for 28 days after the last injection of the study drug.
• Male subjects who are able to father a child must agree to avoid impregnating a partner, to adhere to a highly effective method of contraception and to not donate sperm during the study and for 28 days after the last injection of the study drug.
Inclusion Criteria:
Part 2
• Patient must be ≥ 15 years of age and must have provided written informed consent and assent, where applicable (by patient or legal guardian). Those aged ≥15 to \<18 years must weigh at least 55 kg.
• Patients must have histological, pathological, and/or cytological confirmation of a sarcoma or GIT cancers e.g., esophageal, gastric, pancreatic, colorectal cancer.
• Patients must have suspected FAP expressing sarcoma or GIT cancers and planned for surgery within 60 days (from study imaging).
• Patients must be willing to consent to provide sufficient and adequate tumor tissue samples (formalin fixed, paraffin embedded sample), from their planned surgery after participating in study imaging.
• Adequate renal function as determined by a calculated creatinine clearance ≥ 60 mL/min (Cockcroft Gault equation).
• Women of childbearing potential (WOCBP) must have a negative beta-human chorionic gonadotropin (β-hCG) test and must not be breastfeeding. WOCBP must agree to use a highly effective method of contraception during the study and for 28 days after the last injection of the study drug.
• Male subjects who are able to father a child must agree to avoid impregnating a partner, to adhere to a highly effective method of contraception and to not donate sperm during the study and for 28 days after the last injection of the study drug.
Exclusion Criteria:
Part 1
Patients are excluded from the study if any of the following criteria apply:
• Unlikely to comply with protocol procedures, restrictions and requirements as judged by the Investigator.
• Known pregnancy or breastfeeding.
• Any PET scan done within 10 physical half-lives of the PET agent prior to receiving study intervention.
• Patients participating in another clinical trial at the time of screening for this study.
• Patients who have had systemic anti-cancer therapy administered in the 14 days prior to IP administration.
• Has undergone or plans to undergo PET or single-photon emission computerized tomography (SPECT) imaging with any other FAPi imaging agent within 6 months prior to or after participating in this trial.
• History of QT/QTc interval prolongation, a marked baseline QT/QTc interval prolongation (e.g., repeated demonstration of a QTc interval, calculated with Fridericia's correction, \> 450 milliseconds) or taking medication known to cause QT/QTc prolongation.
• A history of additional risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome).
Exclusion Criteria:
Part 2
• Patients who have had neoadjuvant anti-cancer therapy administered in the 14 days prior to IP administration.
• Evidence of metastatic or advanced, inoperable disease.
• Unlikely to comply with protocol procedures, restrictions and requirements and judged by the investigator to be unsuitable for participation.
• Known pregnancy or breastfeeding.
• Any PET scan done within 10 physical half-lives of the PET agent prior to receiving study intervention.
• Patients participating in another clinical trial at the time of screening for this study.
• Has undergone or plans to undergo PET or SPECT imaging with any other FAPi imaging agent within 6 months prior to or after participating in this trial.
• History of QT/QTc interval prolongation, a marked baseline QT/QTc interval prolongation (e.g., repeated demonstration of a QTc interval, calculated with Fridericia's correction, \> 450 milliseconds) or taking drugs known to cause QT/QTc prolongation.
• A history of additional risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome
COMBINATION_PRODUCT: 64Cu-LNTH-1363S
Metastatic Sarcoma, Esophageal Cancer, Gastric Cancer, Pancreatic Cancer, Colorectal Cancer, Sarcoma
FAPi, Imaging, 64Cu-LNTH-1363S
Study of Olutasidenib and Temozolomide in HGG
Peter M de Blank, MD - Peter.deBlank@cchmc.org
ALL
12 years to 39 years old
PHASE2
NCT06161974
Criteria TarGeT-D study strata definitions
* Stratum A: Patients with localized, intracranial, non-pontine, and non-thalamic IDH 1 mutant Astrocytoma, CNS WHO Grade 3.
* Stratum B: Patients with localized, intracranial, non-pontine, and non-thalamic IDH 1 mutant Astrocytoma, CNS WHO Grade 4.
* Stratum C: Patients with IDH-1 mutant DIPG, primary thalamic and spinal cord IDH-1 mutant HGG.
• Inclusion criteria already met to enroll on TarGeT-SCR (central molecular and histopathologic screening) based on:
• 1) Age: patients must be ≥12 years and ≤39 years of age at the time of enrollment on TarGeT-SCR 1.2) Diagnosis: * Patients with a newly-diagnosed IDH1-mutant HGG including DIPG are eligible. All patients must have tumor tissue from diagnostic biopsy or resection, without exceptions. The diagnosis of HGG, including DIPG, must have been confirmed through TarGeT-SCR. * For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2/3 of the pons, and histopathology consistent with diffuse WHO Grade 2-4 glioma. * All other HGG must be WHO Grade 3 or 4.
• 3) Disease status: There are no disease status requirements for enrollment * Measurable disease is not required. Patients without measurable disease are eligible. * Primary spinal tumor: Patients with a primary spinal HGG are eligible. * Patient must not have metastatic disease.
• Inclusion criteria for assignment to TarGeT-D, for all strata:
• 1 Presence of at Least One Relevant Actionable Somatic Mutation in IDH1 Gene, Detailed Here: * R132H, R132C, R132S, R132G or R132L. * Patients whose tumors harbor other alterations in addition to IDH1 mutation will potentially be eligible following consensus recommendation by the international multidisciplinary molecular screening committee. * Patients with IDH2 mutations are not eligible. * Patients with oligodendroglioma, IDH-mutant and 1p/19q-codeleted are not eligible.
• 2 Weight: Patients must weigh ≥35 Kg (77 lbs) at the time of enrollment on TarGeT-D.
• 3 Performance Level: Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• 4 Prior Therapy 2.4.1 Surgery, radiation, and/or dexamethasone are permissible. Temozolomide administered concurrently with radiotherapy is permissible. Prior administration of bevacizumab is allowed, given at least 42-day washout period is completed prior to beginning treatment on TarGeT-D. No other prior anticancer therapy for HGG will be allowed.
• 4.2 Radiation therapy requirements: RT, delivered via photon or proton beam, must have been administered at a standard dose including 54 Gy in 30 fractions for DIPG, 55-59.4 Gy in 30-33 fractions for other HGG or 45-54 Gy for primary spinal cord HGG. Any variances in the radiotherapy dose within 10% of the standard doses outlined above will be discussed with the Study Chair to confirm eligibility prior to study enrollment.
• 4.3 Timing between diagnosis and start of RT: Patients must have started RT \< 42 calendar days of initial diagnosis defined as the date of diagnostic biopsy or resection; if a patient underwent two upfront surgeries (e.g., biopsy then resection or debulking), this is the date of the second surgery. * Patients in pre-maintenance phase must enroll and start treatment no later than 21 calendar days post-completion of RT. * Patients not in pre-maintenance phase must enroll and start treatment no later than 35 calendar days post-completion of RT.
• 5 Organ Function Requirements 2.5.1 Adequate Bone Marrow Function Defined as: * Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3. * Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment). * Hemoglobin \> 8 g/dL (may be transfused). 2.5.2 Adequate Renal Function Defined as * Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 OR * Maximum serum creatinine based on age/gender as follows: 10 to \< 13 yrs=1.2 mg/dL for males and females. 13 to \< 16 yrs=1.5 mg/dL for males and 1.4 mg/dL for females.
• 5.3 Adequate Liver Function Defined as: * Total bilirubin must be ≤ 1.5 × institutional ULN. * AST(SGOT)/ALT(SGPT) \< 3 × institutional ULN. * Alkaline Phosphatase \< 3 × institutional ULN. 2.5.4 Adequate Neurologic Function Defined as: * Patients with seizure disorder may be enrolled if well-controlled on anticonvulsants that are not a strong inducer or inhibitor of CYP3A4/5. * Patients must be able to swallow oral medications to be eligible for study enrollment.
• 6. Informed consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
• Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to unknown potential risks of fetal and teratogenic adverse events as seen in animal studies. Pregnancy tests must be obtained in girls who are post-menarchal. Patients of childbearing or child fathering potential must agree to use one highly effective method of contraception while being treated on this study and for 3 months after completing therapy. A woman is considered of childbearing potential if she is fertile, following menarche and until becoming post-menopausal unless permanently sterile. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. Male participants should refrain from sperm donation throughout the duration of treatment and for 3 months after completion of therapy. A highly effective contraception method is defined as one that results in a low failure rate (\<1% per year) when used consistently and correctly. The following are considered highly effective contraception methods: * Combined estrogen and progesterone containing hormonal contraception associated with inhibition of ovulation. * Progesterone-only hormonal contraception associated with inhibition of ovulation. * Intra Uterine Device (IUD). * Intra uterine hormone releasing system. * Bilateral tubal occlusion. * Vasectomized partner. * Sexual abstinence (avoiding heterosexual intercourse). * The following contraceptive measures are NOT considered effective: * Progesterone-only hormonal contraception (birth control pill) that that does NOT stop ovulation. * Male or female condom with or without spermicide. * Cap, diaphragm, or sponge with spermicide.
• Using the following types of concomitant medications: * Corticosteroids: Patients receiving corticosteroids are eligible. The use of corticosteroids must be reported. * Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible. * Anti-cancer Agents: Concurrent anti-cancer agents are not allowed with the exception of temozolomide given concurrently with RT and as protocol-instructed post RT maintenance therapy after enrollment on TarGeT-D. * Anticonvulsants: Patients who are receiving enzyme inducing anticonvulsants that are strong inducers of CYP3A4/5 are not eligible. * Strong CYP3A4/5 inducers: Patients who are receiving strong inducers of CYP3A4/5 are not eligible. Strong inducers of CYP3A4/5 should be avoided from 14 days prior to or 5 half-lives (whichever is longer) enrollment to the end of the study. * Patients who are receiving medications known to prolong QTc interval are not eligible * Selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft) should be used with caution but are not contraindicated.
• Other Criteria * Infection: Patients who have an uncontrolled infection are not eligible. * Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible. * Patients with known clinically significant active malabsorption syndrome or other condition that could affect absorption are not eligible. * Patients with malignancy related to HIV or solid organ transplant: known history of HIV, HBV surface antigen positivity or positive HCV antibody are not eligible. Viral testing is not required unless clinically indicated in patients without a known history. * Patients with prior or ongoing clinically significant illness, medical or psychiatric condition, that, in the investigator's opinion, could affect the safety of the participant, or could impair the assessment of study results are not eligible. * Patients with any prior solid organ transplant are not eligible. * Patients with secondary/radiation-related HGG are not eligible. * Patients with metastatic/disseminated HGG who have received CSI are not eligible.
Inclusion Criteria:
• Inclusion criteria already met to enroll on TarGeT-SCR (central molecular and histopathologic screening) based on:
• 1) Age: patients must be ≥12 years and ≤39 years of age at the time of enrollment on TarGeT-SCR 1.2) Diagnosis: * Patients with a newly-diagnosed IDH1-mutant HGG including DIPG are eligible. All patients must have tumor tissue from diagnostic biopsy or resection, without exceptions. The diagnosis of HGG, including DIPG, must have been confirmed through TarGeT-SCR. * For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2/3 of the pons, and histopathology consistent with diffuse WHO Grade 2-4 glioma. * All other HGG must be WHO Grade 3 or 4.
• 3) Disease status: There are no disease status requirements for enrollment * Measurable disease is not required. Patients without measurable disease are eligible. * Primary spinal tumor: Patients with a primary spinal HGG are eligible. * Patient must not have metastatic disease.
• Inclusion criteria for assignment to TarGeT-D, for all strata:
• 1 Presence of at Least One Relevant Actionable Somatic Mutation in IDH1 Gene, Detailed Here: * R132H, R132C, R132S, R132G or R132L. * Patients whose tumors harbor other alterations in addition to IDH1 mutation will potentially be eligible following consensus recommendation by the international multidisciplinary molecular screening committee. * Patients with IDH2 mutations are not eligible. * Patients with oligodendroglioma, IDH-mutant and 1p/19q-codeleted are not eligible.
• 2 Weight: Patients must weigh ≥35 Kg (77 lbs) at the time of enrollment on TarGeT-D.
• 3 Performance Level: Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• 4 Prior Therapy 2.4.1 Surgery, radiation, and/or dexamethasone are permissible. Temozolomide administered concurrently with radiotherapy is permissible. Prior administration of bevacizumab is allowed, given at least 42-day washout period is completed prior to beginning treatment on TarGeT-D. No other prior anticancer therapy for HGG will be allowed.
• 4.2 Radiation therapy requirements: RT, delivered via photon or proton beam, must have been administered at a standard dose including 54 Gy in 30 fractions for DIPG, 55-59.4 Gy in 30-33 fractions for other HGG or 45-54 Gy for primary spinal cord HGG. Any variances in the radiotherapy dose within 10% of the standard doses outlined above will be discussed with the Study Chair to confirm eligibility prior to study enrollment.
• 4.3 Timing between diagnosis and start of RT: Patients must have started RT \< 42 calendar days of initial diagnosis defined as the date of diagnostic biopsy or resection; if a patient underwent two upfront surgeries (e.g., biopsy then resection or debulking), this is the date of the second surgery. * Patients in pre-maintenance phase must enroll and start treatment no later than 21 calendar days post-completion of RT. * Patients not in pre-maintenance phase must enroll and start treatment no later than 35 calendar days post-completion of RT.
• 5 Organ Function Requirements 2.5.1 Adequate Bone Marrow Function Defined as: * Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3. * Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment). * Hemoglobin \> 8 g/dL (may be transfused). 2.5.2 Adequate Renal Function Defined as * Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 OR * Maximum serum creatinine based on age/gender as follows: 10 to \< 13 yrs=1.2 mg/dL for males and females. 13 to \< 16 yrs=1.5 mg/dL for males and 1.4 mg/dL for females.
• 5.3 Adequate Liver Function Defined as: * Total bilirubin must be ≤ 1.5 × institutional ULN. * AST(SGOT)/ALT(SGPT) \< 3 × institutional ULN. * Alkaline Phosphatase \< 3 × institutional ULN. 2.5.4 Adequate Neurologic Function Defined as: * Patients with seizure disorder may be enrolled if well-controlled on anticonvulsants that are not a strong inducer or inhibitor of CYP3A4/5. * Patients must be able to swallow oral medications to be eligible for study enrollment.
• 6. Informed consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
Exclusion Criteria:
• Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to unknown potential risks of fetal and teratogenic adverse events as seen in animal studies. Pregnancy tests must be obtained in girls who are post-menarchal. Patients of childbearing or child fathering potential must agree to use one highly effective method of contraception while being treated on this study and for 3 months after completing therapy. A woman is considered of childbearing potential if she is fertile, following menarche and until becoming post-menopausal unless permanently sterile. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. Male participants should refrain from sperm donation throughout the duration of treatment and for 3 months after completion of therapy. A highly effective contraception method is defined as one that results in a low failure rate (\<1% per year) when used consistently and correctly. The following are considered highly effective contraception methods: * Combined estrogen and progesterone containing hormonal contraception associated with inhibition of ovulation. * Progesterone-only hormonal contraception associated with inhibition of ovulation. * Intra Uterine Device (IUD). * Intra uterine hormone releasing system. * Bilateral tubal occlusion. * Vasectomized partner. * Sexual abstinence (avoiding heterosexual intercourse). * The following contraceptive measures are NOT considered effective: * Progesterone-only hormonal contraception (birth control pill) that that does NOT stop ovulation. * Male or female condom with or without spermicide. * Cap, diaphragm, or sponge with spermicide.
• Using the following types of concomitant medications: * Corticosteroids: Patients receiving corticosteroids are eligible. The use of corticosteroids must be reported. * Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible. * Anti-cancer Agents: Concurrent anti-cancer agents are not allowed with the exception of temozolomide given concurrently with RT and as protocol-instructed post RT maintenance therapy after enrollment on TarGeT-D. * Anticonvulsants: Patients who are receiving enzyme inducing anticonvulsants that are strong inducers of CYP3A4/5 are not eligible. * Strong CYP3A4/5 inducers: Patients who are receiving strong inducers of CYP3A4/5 are not eligible. Strong inducers of CYP3A4/5 should be avoided from 14 days prior to or 5 half-lives (whichever is longer) enrollment to the end of the study. * Patients who are receiving medications known to prolong QTc interval are not eligible * Selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft) should be used with caution but are not contraindicated.
• Other Criteria * Infection: Patients who have an uncontrolled infection are not eligible. * Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible. * Patients with known clinically significant active malabsorption syndrome or other condition that could affect absorption are not eligible. * Patients with malignancy related to HIV or solid organ transplant: known history of HIV, HBV surface antigen positivity or positive HCV antibody are not eligible. Viral testing is not required unless clinically indicated in patients without a known history. * Patients with prior or ongoing clinically significant illness, medical or psychiatric condition, that, in the investigator's opinion, could affect the safety of the participant, or could impair the assessment of study results are not eligible. * Patients with any prior solid organ transplant are not eligible. * Patients with secondary/radiation-related HGG are not eligible. * Patients with metastatic/disseminated HGG who have received CSI are not eligible.
DRUG: Olutasidenib + TMZ
High Grade Glioma, Astrocytoma, Astrocytoma, Grade III, Astrocytoma, Grade IV, Diffuse Intrinsic Pontine Glioma, WHO Grade III Glioma, WHO Grade IV Glioma, Metastatic Brain Tumor, Diffuse Midline Glioma, H3 K27M-Mutant, Thalamus Tumor, Spinal Tumor, IDH1 Mutation, IDH1 R132, IDH1 R132C, IDH1 R132H, IDH1 R132S, IDH1 R132G, IDH1 R132L, Oligodendroglioma