131I-Omburtamab, in Recurrent Medulloblastoma and Ependymoma
NCT ID: NCT04743661
Last Updated: 2024-08-06
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
ACTIVE_NOT_RECRUITING
PHASE2
62 participants
INTERVENTIONAL
2022-04-04
2030-10-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
131I-omburtamab Radioimmunotherapy for Neuroblastoma Central Nervous System/Leptomeningeal Metastases
NCT03275402
177Lu-DTPA-Omburtamab Radioimmunotherapy for Recurrent or Refractory Medulloblastoma
NCT04167618
Molecular and Clinical Risk-Directed Therapy for Infants and Young Children With Newly Diagnosed Medulloblastoma
NCT05535166
MIBG With Dinutuximab +/- Vorinostat
NCT03332667
Antiangiogenic Therapy for Children with Recurrent Medulloblastoma, Ependymoma and ATRT
NCT01356290
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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 (typically using 3 whole-body planar gamma camera imaging and at least 1 head SPECT scan or SPECT/CT) 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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Recurrent Medulloblastoma
This arm aims to estimate 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 will receive 2 therapeutic doses of 50 mCi cRIT 131I-omburtamab during Radioimmunotherapy. 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.
Irinotecan
Irinotecan is a semisynthetic water-soluble analog of camptothecin (a plant alkaloid isolated from Camptotheca acuminata). Irinotecan is available in single-dose amber glass vials in 40 mg (2 mL) and 100 mg (5 mL), 300 mg (15 mL), and 500 mg (25 mL).
Patients on Stratum 1 will be given irinotecan at 50 mg/m2/day IV on Days 1 through 5 of each chemotherapy course.
Temozolomide
An orally administered alkylating agent, a second generation imidazotetrazine. A prodrug of MTIC, temozolomide spontaneously decomposes to MTIC at physiologic pH. Exerts its effect by cross-linking DNA. Temozolomide capsules are available in six different strengths (5, 20, 100, 140, 180, 250 mg). The capsules vary in size, color, and imprint according to strength. In the US, capsules are packaged in 5-count and 14-count bottles.
Patients on Stratum 1 will be given temozolomide at 150 mg/m2/dose PO on Days 1-5 of each chemotherapy course.
Bevacizumab
Bevacizumab is a recombinant humanized anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibody. Bevacizumab is supplied as a clear to slightly opalescent, sterile liquid ready for parenteral administration. Each 400 mg (25 mg/mL, 16 mL fill) glass vial contains bevacizumab with phosphate, trehalose, polysorbate 20, and Sterile Water for Injection.
Patients on Stratum 1 will be given bevacizumab at 10 mg/kg/day IV on Days 1 and 15 of each chemotherapy course, with the exception of the last course of Induction Chemotherapy (i.e., Course 2 or 4) where it will be administered on Day 1 only.
Omburtamab I-131
Omburtamab is a murine IgG1 monoclonal antibody (mAb) against B7-H3 (CD276) manufactured by in vivo growth of the hybridoma cell line without the use of animal-derived components. Omburtamab will be radiolabeled with iodine-131 at a designated radiolabeling facility. 131I-omburtamab is supplied as a sterile, injectable, radioactive product in a vial. Each supplied vial will contain enough radioactivity to prepare 50 mCi of 131I-omburtamab, formulated in 3.5-4 mL of solution. 131I-omburtamab should be administered via an intraventricular access device (i.e., Ommaya catheter or programmable VP shunt). Radioimmunotherapy consists of 56 days.
Patients on Stratum 1 will receive a therapeutic dose of 50 mCi cRIT 131I-omburtamab on Days 8 and 36 of Radioimmunotherapy.
Patients on Stratum 2 will receive a therapeutic dose of 50 mCi cRIT 131I-omburtamab on Days 1 and 29 of Radioimmunotherapy.
Liothyronine
Liothyronine (or equivalent) will be given as premedication for 131I-omburtamab to prevent thyroid accumulation. Liothyronine (or equivalent) will be administered at 25 µg PO, NG, or G-tube (if weight \< 25 kg) or 50 µg PO, NG, or G-tube (if weight ≥ 25 kg) daily starting on Day 1 of Radioimmunotherapy (for Stratum 1 patients) or Day 1 of Dosimetry (for Stratum 2 patients), with a mandated minimum of 7 days before each 131I-omburtamab injection and 14 days after each 131I-omburtamab injection. On the day of the 131I-omburtamab injection, administer any time before the injection.
SSKI
SSKI (potassium iodide) will be given as premedication for 131I-omburtamab to prevent thyroid accumulation. SSKI (potassium iodide) will be administered as 7 drops (\~0.35 mL) PO, NG, or G-tube daily starting on Day 1 of Radioimmunotherapy (for Stratum 1 patients) or Day 1 of Dosimetry (for Stratum 2 patients), with a mandated minimum of 7 days before each 131I-omburtamab injection and 14 days after each 131I-omburtamab injection. On the day of the 131I-omburtamab injection, administer any time before the injection.
Dexamethasone
Dexamethasone will be given as premedication for 131I-omburtamab to prevent possible meningeal inflammatory reaction. Starting within 24 hours prior to each 131I-omburtamab injection, dexamethasone will be administered orally at 0.5 mg (if weight \< 15 kg) or 1 mg (if weight ≥ 15 kg) twice-daily doses for a total of 6 doses to alleviate infusion-related AEs: Two doses starting 24 hours pre-131I-omburtamab injection, two doses on the day of the injection (can be given before or after), and two doses 24 hours post-131I-omburtamab injection.
Antipyretic
An antipyretic (e.g., oral acetaminophen \[15 mg/kg, 650 mg maximum\] or equivalent) will be given as premedication for 131I-omburtamab within 1 to 3 hours before each 131I-omburtamab injection.
Antihistamine
An antihistamine (e.g., IV diphenhydramine \[1 mg/kg, 50 mg maximum\] or equivalent) will be given as premedication for 131I-omburtamab within 1 to 3 hours before each 131I-omburtamab injection.
anti-emetics
An anti-emetic (e.g., IV ondansetron \[0.25 mg/kg, 16 mg maximum\] or equivalent) will be given as premedication for 131I-omburtamab within 1 to 3 hours before each 131I-omburtamab injection.
Recurrent Ependymoma
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. Tumor tissue (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) of cRIT 131I-omburtamab.
Omburtamab I-131
Omburtamab is a murine IgG1 monoclonal antibody (mAb) against B7-H3 (CD276) manufactured by in vivo growth of the hybridoma cell line without the use of animal-derived components. Omburtamab will be radiolabeled with iodine-131 at a designated radiolabeling facility. 131I-omburtamab is supplied as a sterile, injectable, radioactive product in a vial. Each supplied vial will contain enough radioactivity to prepare 50 mCi of 131I-omburtamab, formulated in 3.5-4 mL of solution. 131I-omburtamab should be administered via an intraventricular access device (i.e., Ommaya catheter or programmable VP shunt). Radioimmunotherapy consists of 56 days.
Patients on Stratum 1 will receive a therapeutic dose of 50 mCi cRIT 131I-omburtamab on Days 8 and 36 of Radioimmunotherapy.
Patients on Stratum 2 will receive a therapeutic dose of 50 mCi cRIT 131I-omburtamab on Days 1 and 29 of Radioimmunotherapy.
Liothyronine
Liothyronine (or equivalent) will be given as premedication for 131I-omburtamab to prevent thyroid accumulation. Liothyronine (or equivalent) will be administered at 25 µg PO, NG, or G-tube (if weight \< 25 kg) or 50 µg PO, NG, or G-tube (if weight ≥ 25 kg) daily starting on Day 1 of Radioimmunotherapy (for Stratum 1 patients) or Day 1 of Dosimetry (for Stratum 2 patients), with a mandated minimum of 7 days before each 131I-omburtamab injection and 14 days after each 131I-omburtamab injection. On the day of the 131I-omburtamab injection, administer any time before the injection.
SSKI
SSKI (potassium iodide) will be given as premedication for 131I-omburtamab to prevent thyroid accumulation. SSKI (potassium iodide) will be administered as 7 drops (\~0.35 mL) PO, NG, or G-tube daily starting on Day 1 of Radioimmunotherapy (for Stratum 1 patients) or Day 1 of Dosimetry (for Stratum 2 patients), with a mandated minimum of 7 days before each 131I-omburtamab injection and 14 days after each 131I-omburtamab injection. On the day of the 131I-omburtamab injection, administer any time before the injection.
Dexamethasone
Dexamethasone will be given as premedication for 131I-omburtamab to prevent possible meningeal inflammatory reaction. Starting within 24 hours prior to each 131I-omburtamab injection, dexamethasone will be administered orally at 0.5 mg (if weight \< 15 kg) or 1 mg (if weight ≥ 15 kg) twice-daily doses for a total of 6 doses to alleviate infusion-related AEs: Two doses starting 24 hours pre-131I-omburtamab injection, two doses on the day of the injection (can be given before or after), and two doses 24 hours post-131I-omburtamab injection.
Antipyretic
An antipyretic (e.g., oral acetaminophen \[15 mg/kg, 650 mg maximum\] or equivalent) will be given as premedication for 131I-omburtamab within 1 to 3 hours before each 131I-omburtamab injection.
Antihistamine
An antihistamine (e.g., IV diphenhydramine \[1 mg/kg, 50 mg maximum\] or equivalent) will be given as premedication for 131I-omburtamab within 1 to 3 hours before each 131I-omburtamab injection.
anti-emetics
An anti-emetic (e.g., IV ondansetron \[0.25 mg/kg, 16 mg maximum\] or equivalent) will be given as premedication for 131I-omburtamab within 1 to 3 hours before each 131I-omburtamab injection.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Irinotecan
Irinotecan is a semisynthetic water-soluble analog of camptothecin (a plant alkaloid isolated from Camptotheca acuminata). Irinotecan is available in single-dose amber glass vials in 40 mg (2 mL) and 100 mg (5 mL), 300 mg (15 mL), and 500 mg (25 mL).
Patients on Stratum 1 will be given irinotecan at 50 mg/m2/day IV on Days 1 through 5 of each chemotherapy course.
Temozolomide
An orally administered alkylating agent, a second generation imidazotetrazine. A prodrug of MTIC, temozolomide spontaneously decomposes to MTIC at physiologic pH. Exerts its effect by cross-linking DNA. Temozolomide capsules are available in six different strengths (5, 20, 100, 140, 180, 250 mg). The capsules vary in size, color, and imprint according to strength. In the US, capsules are packaged in 5-count and 14-count bottles.
Patients on Stratum 1 will be given temozolomide at 150 mg/m2/dose PO on Days 1-5 of each chemotherapy course.
Bevacizumab
Bevacizumab is a recombinant humanized anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibody. Bevacizumab is supplied as a clear to slightly opalescent, sterile liquid ready for parenteral administration. Each 400 mg (25 mg/mL, 16 mL fill) glass vial contains bevacizumab with phosphate, trehalose, polysorbate 20, and Sterile Water for Injection.
Patients on Stratum 1 will be given bevacizumab at 10 mg/kg/day IV on Days 1 and 15 of each chemotherapy course, with the exception of the last course of Induction Chemotherapy (i.e., Course 2 or 4) where it will be administered on Day 1 only.
Omburtamab I-131
Omburtamab is a murine IgG1 monoclonal antibody (mAb) against B7-H3 (CD276) manufactured by in vivo growth of the hybridoma cell line without the use of animal-derived components. Omburtamab will be radiolabeled with iodine-131 at a designated radiolabeling facility. 131I-omburtamab is supplied as a sterile, injectable, radioactive product in a vial. Each supplied vial will contain enough radioactivity to prepare 50 mCi of 131I-omburtamab, formulated in 3.5-4 mL of solution. 131I-omburtamab should be administered via an intraventricular access device (i.e., Ommaya catheter or programmable VP shunt). Radioimmunotherapy consists of 56 days.
Patients on Stratum 1 will receive a therapeutic dose of 50 mCi cRIT 131I-omburtamab on Days 8 and 36 of Radioimmunotherapy.
Patients on Stratum 2 will receive a therapeutic dose of 50 mCi cRIT 131I-omburtamab on Days 1 and 29 of Radioimmunotherapy.
Liothyronine
Liothyronine (or equivalent) will be given as premedication for 131I-omburtamab to prevent thyroid accumulation. Liothyronine (or equivalent) will be administered at 25 µg PO, NG, or G-tube (if weight \< 25 kg) or 50 µg PO, NG, or G-tube (if weight ≥ 25 kg) daily starting on Day 1 of Radioimmunotherapy (for Stratum 1 patients) or Day 1 of Dosimetry (for Stratum 2 patients), with a mandated minimum of 7 days before each 131I-omburtamab injection and 14 days after each 131I-omburtamab injection. On the day of the 131I-omburtamab injection, administer any time before the injection.
SSKI
SSKI (potassium iodide) will be given as premedication for 131I-omburtamab to prevent thyroid accumulation. SSKI (potassium iodide) will be administered as 7 drops (\~0.35 mL) PO, NG, or G-tube daily starting on Day 1 of Radioimmunotherapy (for Stratum 1 patients) or Day 1 of Dosimetry (for Stratum 2 patients), with a mandated minimum of 7 days before each 131I-omburtamab injection and 14 days after each 131I-omburtamab injection. On the day of the 131I-omburtamab injection, administer any time before the injection.
Dexamethasone
Dexamethasone will be given as premedication for 131I-omburtamab to prevent possible meningeal inflammatory reaction. Starting within 24 hours prior to each 131I-omburtamab injection, dexamethasone will be administered orally at 0.5 mg (if weight \< 15 kg) or 1 mg (if weight ≥ 15 kg) twice-daily doses for a total of 6 doses to alleviate infusion-related AEs: Two doses starting 24 hours pre-131I-omburtamab injection, two doses on the day of the injection (can be given before or after), and two doses 24 hours post-131I-omburtamab injection.
Antipyretic
An antipyretic (e.g., oral acetaminophen \[15 mg/kg, 650 mg maximum\] or equivalent) will be given as premedication for 131I-omburtamab within 1 to 3 hours before each 131I-omburtamab injection.
Antihistamine
An antihistamine (e.g., IV diphenhydramine \[1 mg/kg, 50 mg maximum\] or equivalent) will be given as premedication for 131I-omburtamab within 1 to 3 hours before each 131I-omburtamab injection.
anti-emetics
An anti-emetic (e.g., IV ondansetron \[0.25 mg/kg, 16 mg maximum\] or equivalent) will be given as premedication for 131I-omburtamab within 1 to 3 hours before each 131I-omburtamab injection.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Patients must have disease, defined as tumor 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. Patients may have tumor cells in CSF with or without radiographic evidence of disease at time of enrollment.
* Patients must be \< 22 years of age at time of enrollment.
* 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, 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 patient due to underlying medical conditions or declined by 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.
* 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) - 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 antibody treatment and agents with known prolonged half-lives - Patient must have recovered from any acute toxicity potentially related to the agent and received last dose of the agent ≥ 21 days prior to study enrollment.
* Radiation - Patients must have had their last fraction of:
1. Craniospinal irradiation, whole brain radiation, total body irradiation, or radiation to \>= 50% of pelvis or spine 24 weeks prior to study enrollment. Tumor designated as "measurable" for protocol purposes must not have received radiation within 12 weeks prior to study enrollment.
2. Focal radiation to areas of symptomatic metastatic disease at least 14 days prior to study enrollment.
* Stem Cell Transplant (SCT) - For autologous SCT \>= 3 months must have elapsed 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 - Patients must have:
1. Peripheral absolute neutrophil count (ANC) ≥ 1 x 10\^9/ L (must not have received G-CSF within 7 days prior to enrollment or pegfilgrastim within 14 days prior to enrollment)
2. Platelet count ≥ 100 x 10\^9/ L (unsupported, defined as no platelet transfusion within 7 days prior to study enrollment)
3. Hemoglobin ≥ 8.0 g/dL (may receive packed red blood cell \[PRBC\] transfusions)
4. Serum creatinine based on age/gender. Patients that do not meet the criteria in Table 1 but have a 24 hour Creatinine Clearance or GFR (radioisotope or iothalamate) ≥ 70 mL/min/1.73 m\^2 are eligible.
5. 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.
6. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
7. ALT (SGPT) and AST (SGOT) \< 5 x institutional upper limit of normal (ULN)
8. INR/PT ≤ 1.5 x institutional upper limit of normal (ULN)
* Hypertension must be well controlled (≤ 95th percentile) on stable doses of medication.
* Patients must have recovered from any surgical procedure before enrolling on this study.
* 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.
* 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.
* The patient or parent/guardian can understand the consent and is willing to sign a written informed consent document according to institutional guidelines.
* 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.
* 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:
1. 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.
2. 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
1. 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)
2. Platelet count ≥ 100 x 10\^9/ L (unsupported, defined as no platelet transfusion within 7 days prior to study enrollment)
3. Hemoglobin ≥ 8.0 g/dL (may receive PRBC transfusions)
4. 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.
5. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) for age
6. 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.
* 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
* Patients must not have previously received the combination of bevacizumab, irinotecan, and temozolomide therapy.
* Patients with a serious or non-healing wound, ulcer, or bone fracture are not eligible for this study.
* Patients must not have a history of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to study enrollment.
* Patients must not have a known bleeding diathesis or coagulopathy.
* 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.
* 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.
* Patients must not have evidence of new CNS hemorrhage on baseline MRI obtained within 14 days prior to study enrollment.
* Patients with 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.
* Patients must not have serious and inadequately controlled cardiac arrhythmia.
* Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies are not eligible.
* Patients must not be currently taking NSAIDS, clopidrogel, dipyridamole, or aspirin therapy \> 81 mg/day.
* 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 currently receiving any of the following medications and cannot be discontinued 7 days prior to enrollment are ineligible:
1. 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
2. Substrates of CYP3A4/5 with a narrow therapeutic index
3. 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.
* 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.
* 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.
* 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.
21 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Cancer Institute (NCI)
NIH
Memorial Sloan Kettering Cancer Center
OTHER
Y-mAbs Therapeutics
INDUSTRY
Pediatric Brain Tumor Consortium
NETWORK
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Matthias Karajannis, MD, MS
Role: PRINCIPAL_INVESTIGATOR
Memorial Sloan Kettering Cancer Center
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Children's Hospital Los Angeles
Los Angeles, California, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Countries
Review the countries where the study has at least one active or historical site.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Informed Consent Form
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2021-00773
Identifier Type: REGISTRY
Identifier Source: secondary_id
PBTC-058
Identifier Type: OTHER
Identifier Source: secondary_id
PBTC-058
Identifier Type: OTHER
Identifier Source: secondary_id
PBTC-058
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.