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Testing a New Anti-Cancer Drug, 131I-Omburtamab, in Recurrent Medulloblastoma or Ependymoma

Trial Status: Approved

This phase II trial studies the effect of 131I-omburtamab compared to usual chemotherapy in treating patients with medulloblastoma that has come back (recurrent) (Stratum 1), and the effect of 131I-omburtamab in treating patients with recurrent ependymoma (Stratum 2). Patients in both strata receive 131I-omburtamab, a monoclonal antibody called 8H9 linked to a radioactive agent called iodine 131. 8H9 attaches to B7H3 positive tumor cells in a targeted way and delivers iodine 131 to kill them. Patients in Stratum 1 receive the usual chemotherapy drugs, temozolomide and irinotecan, that work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Patients in Stratum 1 also receive the usual drug bevacizumab, which may stop or slow tumor cells by blocking the growth of new blood vessels necessary for tumor growth. Adding a new drug called 131I-omburtamab to the usual chemotherapy may lower the chance of recurrent medulloblastoma growing or spreading (Stratum 1). Giving 131I-omburtamab may also be used safely to treat patients with recurrent ependymoma (Stratum 2).

Inclusion Criteria

  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients with a histologically confirmed diagnosis of medulloblastoma that is recurrent, progressive, or refractory to standard therapy. All tumors must have histologic verification at either the time of initial diagnosis or recurrence * Note: For this study, refractory disease is specifically defined as the presence of persistent abnormality on conventional magnetic resonance imaging (MRI) that is further distinguished by histology (tissue sample) or advanced imaging, i.e., diffusion weighted sequences or MR spectroscopy
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients must have disease, defined as tumor that is measurable 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
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients may have tumor cells in the CSF with or without radiographic evidence of disease at the time of enrollment
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients must be < 22 years of age at the time of enrollment
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Protocol treatment with radioimmunotherapy (131I-omburtumab) will require the presence of an appropriate intraventricular access device (e.g., programmable ventriculoperitoneal [VP] shunt or Ommaya reservoir). Patients are not required to have an existing programmable VP shunt or Ommaya at the time of study enrollment but must be willing and able to undergo a surgical procedure to have one placed prior to radioimmunotherapy. * Note: Patients with an existing intraventricular VP shunt without a programmable component must be willing and able to undergo modification of the shunt before treatment with 131I-omburtumab.
  • STRATUM 1 ENROLLMENT: Patients must have recurrent, progressive, or refractory medulloblastoma after prior craniospinal irradiation (CSI) therapy with or without prior chemotherapy, unless CSI is contraindicated or determined to be not in the best interest of the patient due to underlying medical conditions or declined by the patient/family. Patients must have experienced no more than two recurrences of medulloblastoma or have refractory disease * Note: Patients with contraindications to radiation therapy are still eligible.
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients must have received their last dose of known myelosuppressive anticancer therapy at least 21 days (3 weeks) prior to enrollment or at least 42 days (6 weeks) if prior nitrosourea
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: 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
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Monoclonal antibody treatment 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 >= 21 days prior to study enrollment
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients must have had their last fraction of: * Craniospinal irradiation, whole brain radiation, total body irradiation, or radiation to >= 50% of pelvis or spine 24 weeks prior to study enrollment. The tumor designated as “measurable” for protocol purposes must not have received radiation within 12 weeks prior to study enrollment * Focal radiation to areas of symptomatic metastatic disease at least 14 days prior to study enrollment.
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: For autologous stem cell transplant (SCT), >= 3 months must have elapsed prior to study enrollment
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment. A baseline detailed neurological exam should clearly document the neurological status of the patient at the time of study enrollment
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients with seizure disorders may be enrolled if seizures are controlled and on non-enzyme inducing anticonvulsants. Patients must not be taking enzyme-inducing antiepileptic medicines within 1 week prior to study enrollment
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Karnofsky performance scale (KPS for > 16 years of age) or Lansky performance score (LPS for =< 16 years of age) assessed within 2 weeks prior to study 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
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Peripheral absolute neutrophil count (ANC) >= 1 x 10^9/ L (must not have received granulocyte colony-stimulating factor (G-CSF) within the 7 days prior to enrollment or pegfilgrastim within the 14 days prior to enrollment)
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Platelet count >= 100 x 10^9/ L (unsupported, defined as no platelet transfusion within 7 days prior to study enrollment)
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Hemoglobin >= 8.0 g/dL (may receive packed red blood cell [PRBC] transfusions)
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Serum creatinine based on age/gender as noted below. Patients that do not meet the criteria below but have a 24 hour creatinine clearance or glomerular filtration rate (GFR) (radioisotope or iothalamate) >= 70 mL/min/1.73 m^2 are eligible * Serum creatinine for age/gender ** 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 year; 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)
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Urine protein should be screened by dipstick analysis. If protein >= 2+ on dipstick, then Urine Protein Creatinine (UPC) ratio should be calculated. If UPC ratio > 0.5, 24-hour urine protein should be obtained, and the level should be < 1000 mg/24 hours for patient enrollment * Note: UPC ratio of spot urine is an estimation of the 24-urine protein excretion – a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) and aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) < 5 x institutional upper limit of normal (ULN)
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: International normalized ratio (INR)/prothrombin time (PT) =< 1.5 x institutional upper limit of normal (ULN)
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Hypertension must be well controlled (=< 95th percentile) on stable doses of medication
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients must have recovered from any surgical procedure before enrolling on this study (see table below for examples of major, intermediate, and minor surgical procedures): * Patients with a major surgical procedure within 28 days prior to enrollment should be excluded * Patients with an intermediate surgical procedure within 14 days prior to enrollment should be excluded * For minor surgical procedures (including Broviac line or infusaport placement), patients should not receive the first planned dose of bevacizumab until the wound is healed and at least 7 days have elapsed
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients who are known to be Human immunodeficiency virus (HIV)-infected must be on effective anti-retroviral therapy with undetectable viral load within 6 months prior to study enrollment
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: For patients with known evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients with a known history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with known HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients who are receiving dexamethasone at a stable or decreasing dose for at least 7 days prior to study enrollment are eligible
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients must be off all colony-forming growth factor(s) for at least 1 week prior to enrollment (e.g., filgrastim, sargramostim, or erythropoietin) or at least 2 weeks for pegfilgrastim
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Pregnant women are excluded from this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies. Female patients of childbearing potential must have a negative serum or urine pregnancy test prior to enrollment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: 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 6 months after the completion of bevacizumab therapy
  • STRATUM 1 - ELIGIBILITY CRITERIA FOR ENROLLMENT: The patient or parent/guardian can understand the consent and is willing to sign a written informed consent document according to institutional guidelines
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR SCREENING: For patients with a histological diagnosis of ependymoma, a screening consent for B7H3 must be obtained prior to enrollment on PBTC-058
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR SCREENING: Patients must have evidence of tumor reactivity for B7H3 (CD276) to be eligible for treatment. Results from prior testing of tumor reactivity for B7H3 (CD276) using a Clinical Laboratory Improvement Act (CLIA)-certified immunohistochemistry (IHC) assay may be used. For patients who do not have prior B7H3 testing results from a CLIA lab, samples must be sent to MSKCC within 3 days of reservation
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR SCREENING: Patients with a histologically confirmed diagnosis of ependymoma that is recurrent, progressive, or refractory to standard therapy. All tumors must have histologic verification at either the time of initial diagnosis or recurrence * Note: For this study, refractory disease is specifically defined as the presence of persistent abnormality on conventional MRI that is further distinguished by histology (tissue sample) or advanced imaging, i.e., diffusion weighted sequences or MR spectroscopy.
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR SCREENING: Patients may have tumor cells in the CSF with or without radiographic evidence of disease at the time of screening
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR SCREENING: Patients must be < 22 years of age at the time of screening
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR SCREENING: Patients screened for this trial should be expected to meet the criteria for treatment
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients with a histologically confirmed diagnosis of ependymoma that is recurrent or progressive to standard therapy. All tumors must have histologic verification at either the time of initial diagnosis or recurrence
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients must be positive for B7H3 reactivity by IHC performed in a CLIA-certified lab
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients may have tumor cells in the CSF with or without radiographic evidence of disease at the time of enrollment
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients must be < 22 years of age at the time of enrollment
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients must have recurrent or refractory ependymoma after having received either focal or craniospinal irradiation (CSI) therapy, unless CSI is contraindicated or declined by the patient/family. There are no restrictions on the number of prior recurrences for this stratum. * Note: Patients with contraindications to radiation therapy are still eligible.
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients must have received their last dose of known myelosuppressive anticancer therapy at least 21 days (3 weeks) prior to enrollment or at least 42 days (6 weeks) if prior nitrosourea
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Biologic or investigational agent (anti-neoplastic): Patients 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
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Monoclonal antibody treatment and agents with known prolonged half-lives: Patients must have recovered from any acute toxicity potentially related to the agent and received their last dose of the agent >= 21 days prior to study enrollment
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients must have had their last fraction of: * Craniospinal irradiation, whole brain radiation, total body irradiation or radiation to >= 50% of pelvis or spine 24 weeks prior to study enrollment. The tumor designated as “measurable” for protocol purposes must not have received radiation within 12 weeks prior to study enrollment * Focal radiation to areas of symptomatic metastatic disease 14 days prior to study enrollment
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment. A baseline detailed neurological exam should clearly document the neurological status of the patient at the time of study enrollment
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients with seizure disorders may be enrolled if seizures are controlled and on non-enzyme inducing anticonvulsants. Patients must not be taking enzyme-inducing antiepileptic medicines within 1 week prior to study enrollment
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Karnofsky performance scale (KPS for > 16 years of age) or Lansky performance score (LPS for =< 16 years of age) assessed within 2 weeks prior to study 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
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Peripheral absolute neutrophil count (ANC) >= 1 x 10^9/ L (must not have received G-CSF within the 7 days prior to enrollment or pegfilgrastim within the 14 days prior to enrollment)
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Platelet count >= 100 x 10^9/ L (unsupported, defined as no platelet transfusion within 7 days prior to study enrollment)
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Hemoglobin >= 8.0 g/dL (may receive PRBC transfusions)
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Serum creatinine based on age/gender as noted below. Patients that do not meet the criteria below but have a 24 hour creatinine clearance or GFR (radioisotope or iothalamate) >= 70 mL/min/1.73 m^2 are eligible * Serum creatinine for age/gender ** 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 year; 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)
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) for age
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: ALT (SGPT) and AST (SGOT) < 5 x institutional upper limit of normal (ULN) for age
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients who are known to be Human immunodeficiency virus (HIV)-infected must be on effective anti-retroviral therapy with undetectable viral load within 6 months prior to study enrollment
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients with known evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients with a known history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with known HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients who are receiving dexamethasone at a stable or decreasing dose for at least 7 days prior to study enrollment are eligible
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Patients must be off all colony- forming growth factor(s) for at least 1 week prior to enrollment (e.g., filgrastim, sargramostim or erythropoietin) or at least 2 weeks for pegfilgrastim
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Pregnant women are excluded from this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies. Female patients of childbearing potential must have a negative serum or urine pregnancy test prior to enrollment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: 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 40 days after the last dose of 131I-omburtamab
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: The patient or parent/guardian can understand the consent and is willing to sign a written informed consent document according to institutional guidelines
  • STRATUM 2 - ELIGIBILITY CRITERIA FOR ENROLLMENT: Protocol treatment with radioimmunotherapy (131I-omburtumab) will require the presence of an appropriate intraventricular access device (e.g., programmable ventriculoperitoneal [VP] shunt or Ommaya reservoir). Patients are not required to have an existing programmable VP shunt or Ommaya at the time of study enrollment but must be willing and able to undergo a surgical procedure to have one placed prior to radioimmunotherapy. * Note: Patients with an existing intraventricular VP shunt without a programmable component must be willing and able to undergo modification of the shunt before treatment with 131I-omburtumab.

Exclusion Criteria

  • STRATUM 1: Patients must not have previously received the combination of bevacizumab, irinotecan, and temozolomide therapy
  • STRATUM 1: Patients with a serious or non-healing wound, ulcer, or bone fracture are not eligible for this study
  • STRATUM 1: Patients must not have a history of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to study enrollment
  • STRATUM 1: Patients must not have a known bleeding diathesis or coagulopathy
  • STRATUM 1: Patients must not have had significant vascular disease (e.g., aortic aneurysm requiring surgical repair, deep venous or arterial thrombosis) within the last 6 months prior to study enrollment
  • STRATUM 1: Patients must not have a known thrombophilic condition (i.e., protein S, protein C or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocysteinemia or antiphospholipid antibody syndrome). Testing is not required in patients without thrombophilic history
  • STRATUM 1: Patients must not have evidence of new central nervous system (CNS) hemorrhage on baseline MRI obtained within 14 days prior to study enrollment
  • STRATUM 1: Patients with a history of stroke, myocardial infarction, transient ischemic attack (TIA), severe or unstable angina, peripheral vascular disease, or grade II or greater congestive heart failure within the past 6 months are not eligible
  • STRATUM 1: Patients must not have serious and inadequately controlled cardiac arrhythmia
  • STRATUM 1: Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies are not eligible
  • STRATUM 1: Patients must not be currently taking non-steroidal anti-inflammatory drugs (NSAIDS), clopidogrel, dipyridamole, or aspirin therapy > 81 mg/day
  • STRATUM 1: Female patients who are breastfeeding are not eligible for this study unless they agree not to breastfeed
  • STRATUM 1: 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
  • STRATUM 1: Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen for this trial
  • STRATUM 1: Patients who are receiving any other anti-cancer or investigational drug therapy are ineligible
  • STRATUM 1: Patients currently receiving any of the following medications and cannot be discontinued 7 days prior to enrollment are ineligible: * Known strong and moderate inducers or inhibitors of CYP3A4/5, including enzyme-inducing anti-convulsant drugs (EIACDs), grapefruit, echinacea, grapefruit hybrids, pummelos, starfruit, and Seville oranges * Substrates of CYP3A4/5 with a narrow therapeutic index * Herbal preparations/medications (except for vitamins) including, but not limited to: St. John’s wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, black cohosh and ginseng. Patients should stop using all herbal medications and dietary supplements at least 7 days prior to enrollment
  • STRATUM 1: Patients who in the opinion of the investigator are unwilling or unable to return for required follow-up visits or obtain follow-up studies required to assess toxicity to therapy or to adhere to drug administration plan, other study procedures, and study restrictions
  • STRATUM 2: Female patients who are breastfeeding are not eligible for this study unless they agree not to breastfeed
  • STRATUM 2: 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
  • STRATUM 2: Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen for this trial
  • STRATUM 2: Patients who are receiving any other anti-cancer or investigational drug therapy are ineligible
  • STRATUM 2: Patients who in the opinion of the investigator are unwilling or unable to return for required follow-up visits or obtain follow-up studies required to assess toxicity to therapy or to adhere to drug administration plan, other study procedures, and study restrictions

Location information is not yet available.

PRIMARY OBJECTIVES:

I. To estimate the event-free survival (EFS) of patients with relapsed medulloblastoma treated with irinotecan, temozolomide, bevacizumab, and compartmental radioimmunotherapy (cRIT) iodine I 131 omburtamab (131I-omburtamab). (Stratum 1 – Recurrent Medulloblastoma)

II. To assess feasibility of incorporating cRIT 131I-omburtamab for patients with recurrent ependymoma. (Stratum 2 – Recurrent Ependymoma)

SECONDARY OBJECTIVES:

I. To estimate the overall survival (OS) of patients with recurrent medulloblastoma treated on this study including intraOmmaya 131I-omburtamab. (Stratum 1 – Recurrent Medulloblastoma)

II. To assess the B7H3 expression profile on ependymoma tumors. (Stratum 2 – Recurrent Ependymoma)

III. To estimate the EFS and OS of patients with recurrent ependymoma following incorporation of intraOmmaya 131I-omburtamab. (Stratum 2 – Recurrent Ependymoma)

IV. To assess dosimetry to whole-body, organs, cerebrospinal fluid (CSF), and/or tumor (if applicable). (Stratum 2 – Recurrent Ependymoma)

V. To determine the acute and cumulative toxicities of serial injections of cRIT 131I-omburtamab. (Both strata)

EXPLORATORY OBJECTIVE:

I. To explore the significance of cell free deoxyribonucleic acid (cfDNA) and exosome signature in CSF and blood before and after 131I-omburtamab in assessing minimal residual disease. (Both strata)

OUTLINE: Patients are assigned to 1 of 2 strata.

STRATUM 1 (MEDULLOBLASTOMA):

INDUCTION: Patients receive temozolomide orally (PO) on days 1-5, irinotecan intravenously (IV) over 90 minutes on days 1-5, and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 2 or 4 courses in the absence of disease progression or unacceptable toxicity.

RADIOIMMUNOTHERAPY: Beginning 4-6 weeks after induction, patients with stable disease (SD) or better receive 131I-omburtamab by injection via intraventricular access device on day 1. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients temozolomide PO on days 1-5, irinotecan IV over 90 minutes on days 1-5, and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 8 or 10 courses (total of 12 courses induction + maintenance) in the absence of disease progression or unacceptable toxicity.

STRATUM 2 (EPENDYMOMA): Patients receive 131I-omburtamab by injection via intraventricular access device on day 1. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for year 1, every 4 months for year 2, and then every 6 months for years 3-5.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Pediatric Brain Tumor Consortium

Principal Investigator
Matthias A. Karajannis

  • Primary ID PBTC-058
  • Secondary IDs NCI-2021-00773
  • Clinicaltrials.gov ID NCT04743661