131I-Omburtamab, in Recurrent Medulloblastoma and Ependymoma

  • STATUS
    Recruiting
  • End date
    Jul 30, 2030
  • participants needed
    62
  • sponsor
    Pediatric Brain Tumor Consortium
Updated on 25 April 2022

Summary

A Phase 2 study investigating the addition of cRIT 131I-omburtamab to irinotecan, temozolomide, and bevacizumab for patients with recurrent medulloblastoma. A feasibility cohort is included to assess the feasibility of incorporating cRIT 131I-omburtamab for patients with recurrent ependymoma.

Direct intraventricular delivery of radiolabeled tumor-specific antibodies may aid in both the detection and treatment of recurrent disease for these highly specific pediatric patients with recurrent tumors.

Description

Stratum 1: This is a phase 2 single-arm open-label study that will define event-free survival (EFS) and overall survival (OS) following therapy with irinotecan, temozolomide, bevacizumab, and compartmental (intraOmmaya) radioimmunotherapy (cRIT) 131I-omburtamab in patients with recurrent medulloblastoma. Patients with recurrent medulloblastoma will undergo surgery if feasible prior to study entry, followed by Induction Chemotherapy with irinotecan, temozolomide, and bevacizumab on study as per the Children's Oncology Group (COG) trial ACNS0821. Following 2 or 4 courses of chemotherapy and if radiographic disease status is stable or improved, patients may continue to Radioimmunotherapy to receive 2 therapeutic doses (50 mCi each) of cRIT 131I-omburtamab. Following Radioimmunotherapy, patients may resume to Maintenance Chemotherapy with irinotecan, temozolomide, and bevacizumab for up to 12 total courses of chemotherapy or until disease progression, whichever occurs sooner. The primary comparison for this study will be the medulloblastoma cohort treated on ACNS0821 on the irinotecan + temozolomide + bevacizumab arm (N=52).

Stratum 2: This is a feasibility cohort. The primary objective is to assess feasibility of incorporating cRIT 131I-omburtamab for patients with recurrent ependymoma and to assess dosimetry. Patients must have progressed after initial surgery, radiation therapy, or other therapies. Patients will undergo surgery (if feasible) prior to study entry with the goal of achieving stable or better disease. Tumors (archived or new) will be tested for B7H3 prior to enrollment. If positive, patients will enroll on Stratum 2 and receive one dosimetry dose (2 mCi) of cRIT 131I-omburtamab with nuclear medicine scintigraphy using SPECT during the Dosimetry Course (14 days in length). Following the Dosimetry Course and within 2 weeks of the dosimetry dose, patients may continue to Radioimmunotherapy to receive 2 therapeutic doses (50 mCi each) of cRIT 131I-omburtamab.

Details
Condition Recurrent Medulloblastoma, Recurrent Ependymoma
Treatment Dexamethasone, bevacizumab, Temozolomide, Irinotecan, Antihistamine, Liothyronine, Antipyretic, Omburtamab I-131, SSKI, SSKI, anti-emetics, anti-emetics
Clinical Study IdentifierNCT04743661
SponsorPediatric Brain Tumor Consortium
Last Modified on25 April 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Stratum 2
For patients with histological diagnosis of ependymoma, screening consent for B7H3 must be obtained prior to enrollment on PBTC-058
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 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
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 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
Patients may have tumor cells in CSF with or without radiographic evidence of disease at time of screening
Patients must be < 22 years of age at the time of screening
Potential Eligibility for Study Enrollment - Patients screened for this trial should be expected to meet criteria for treatment as outlined in the protocol
INCLUSION CRITERIA FOR ENROLLMENT: Stratum 2
Patients with histologically confirmed diagnosis of ependymoma that is recurrent, progressive, or refractory to standard therapy. All tumors must have histologic verification at either time of initial diagnosis or recurrence
Patients must be positive for B7H3 reactivity by IHC performed in a CLIA-certified lab
Patients may have tumor cells in CSF with or without radiographic evidence of disease at the time of enrollment. Patients are not required to have measurable or evaluable disease at time of study enrollment
Patients must be < 22 years of age at the time of enrollment
Intraventricular Access Device - Protocol treatment with radioimmunotherapy (131I-omburtamab) 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 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-omburtamab
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
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 prior nitrosourea
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
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
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
Patients with neurological deficits should have deficits stable for a minimum of 1
week prior to enrollment. A baseline detailed neurological exam should clearly
document neurological status of the patient at time of study 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
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
Organ Function
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)
Platelet count ≥ 100 x 10^9/ L (unsupported, defined as no platelet transfusion within 7 days prior to study enrollment)
Hemoglobin ≥ 8.0 g/dL (may receive PRBC transfusions)
Serum creatinine based on age/gender. Patients that do not meet the criteria but have a 24 hour Creatinine Clearance or GFR (radioisotope or iothalamate) ≥ 70 mL/min/1.73 m^2 are eligible
Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) for age
ALT (SGPT) and AST (SGOT) < 5 x institutional upper limit of normal (ULN) for age
HIV Infected Individuals - 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
Hep B Chronically Infected Individuals - For patients with known evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
Hep C (HCV) Infected Individuals - 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
Corticosteroids - Patients who are receiving dexamethasone at a stable or decreasing dose for at least 7 days prior to study enrollment are eligible
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) or at least 2 weeks for pegfilgrastim
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
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
The patient or parent/guardian can understand the consent and is willing to sign a written informed consent document according to institutional guidelines

Exclusion Criteria

Stratum 2
Female patients who are breastfeeding are not eligible for this study unless they agree not to breastfeed
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 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
Patients who are receiving any other anti-cancer or investigational drug therapy are ineligible
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
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