Indoximod + Chemotherapy/Radiation for Pediatric Brain Cancer
Trial Summary
Do I have to stop taking my current medications for the trial?
The trial protocol does not specify if you must stop taking your current medications. However, you must be 14 days from any investigational agent or prior cytotoxic therapy, with specific longer periods for certain treatments. Seizure disorders must be well controlled on antiepileptic medication.
What data supports the idea that Indoximod + Chemotherapy/Radiation for Pediatric Brain Cancer is an effective treatment?
The available research shows that temozolomide, a drug used in combination with other treatments for pediatric brain cancer, has shown some effectiveness. In a study, patients with high-grade gliomas who received temozolomide and lomustine had a median survival of 17.6 months, with 60% surviving one year and 40% surviving two years. However, there were significant side effects, including myelosuppression and myelodysplasia, which are serious blood-related conditions. While temozolomide has shown promise, the data also highlights the challenges and risks associated with its use. There is no specific data on Indoximod in the provided information, so its effectiveness in combination with chemotherapy and radiation for pediatric brain cancer cannot be directly assessed from the available research.12345
What safety data is available for Indoximod and chemotherapy/radiation in pediatric brain cancer treatment?
The safety data for the treatment involving temozolomide (TMZ) and lomustine (CCNU) in pediatric brain cancer includes findings from several studies. A phase I trial determined the maximum tolerated dose (MTD) of TMZ with lomustine, noting dose-limiting myelosuppression and thrombocytopenia at higher doses. The MTD was established at 160 mg/m²/day for TMZ with 90 mg/m² lomustine. Radiographic changes post-radiation therapy (RT) complicated early tumor progression assessment, and metastatic disease was common before death. Another study highlighted high-grade hematotoxicity as a frequent side effect in TMZ/lomustine therapy. Overall, TMZ is noted for a lower toxicity profile compared to traditional chemotherapy agents, making it a candidate for combined radio-chemotherapy treatments.15678
Is the drug combination of Cyclophosphamide, Etoposide, Full-dose Radiation, Lomustine, and Temozolomide promising for treating pediatric brain cancer?
What is the purpose of this trial?
Indoximod was developed to inhibit the IDO (indoleamine 2,3-dioxygenase) enzymatic pathway, which is important in the natural regulation of immune responses. This potent immune suppressive mechanism has been implicated in regulating immune responses in settings as diverse as infection, tissue/organ transplant, autoimmunity, and cancer. By inhibiting the IDO pathway, we hypothesize that indoximod will improve antitumor immune responses and thereby slow the growth of tumors.The central clinical hypothesis for the GCC1949 study is that inhibiting the pivotal IDO pathway by adding indoximod immunotherapy during chemotherapy and/or radiation is a potent approach for breaking immune tolerance to pediatric tumors that will improve outcomes, relative to standard therapy alone.This is an NCI-funded (R01 CA229646, MPI: Johnson and Munn) open-label phase 2 trial using indoximod-based combination chemo-radio-immunotherapy for treatment of patients age 3 to 21 years who have progressive brain cancer (glioblastoma, medulloblastoma, or ependymoma), or newly-diagnosed diffuse intrinsic pontine glioma (DIPG). Statistical analysis will stratify patients based on whether their treatment plan includes up-front radiation (or proton) therapy in combination with indoximod. Central review of tissue diagnosis from prior surgery is required, except non-biopsied DIPG. This study will use the "immune-adapted Response Assessment for Neuro-Oncology" (iRANO) criteria for measurement of outcomes. Planned enrollment is up to 140 patients.
Research Team
Theodore S Johnson, MD, PhD
Principal Investigator
Augusta University
Eligibility Criteria
This trial is for children and young adults aged 3 to 21 with progressive brain cancers like glioblastoma, medulloblastoma, ependymoma, or newly diagnosed DIPG. They must be able to swallow pills, have a certain level of physical function (Lansky/Karnofsky score ≥50%), controlled seizures if present, and not have had recent treatments or other specific conditions.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Radiation
Participants receive up-front radiation therapy in combination with indoximod
Chemo-immunotherapy
Participants receive indoximod with oral temozolomide as part of the Core Regimen
Follow-up
Participants are monitored for safety and effectiveness after treatment
Salvage Regimen
Participants may opt to continue access to indoximod with alternative chemotherapy after progression
Treatment Details
Interventions
- Cyclophosphamide
- Etoposide
- Full-dose Radiation
- Indoximod
- Lomustine
- Partial Radiation
- Temozolomide
Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
- Rheumatoid arthritis
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
- Rheumatoid arthritis
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
- Rheumatoid arthritis
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
Find a Clinic Near You
Who Is Running the Clinical Trial?
Theodore S. Johnson
Lead Sponsor
National Cancer Institute (NCI)
Collaborator
Emory University
Collaborator
Augusta University
Collaborator