Nivolumab + Methotrexate/5-Azacytidine for Recurrent Brain Tumors
Trial Summary
What is the purpose of this trial?
The goal of this clinical trial is to assess the safety, toxicity, and antitumor activity of fourth ventricular infusions of nivolumab plus 5-azacytidine for recurrent ependymoma and nivolumab plus methotrexate for recurrent medulloblastoma and other CNS malignancies. Additionally, the study will explore immunologic responses to nivolumab. The hypothesis is that local administration of nivolumab, an immune checkpoint inhibitor, is safe and will lead to even more robust treatment responses when administered following 5-azacytidine in patients with recurrent ependymoma or methotrexate in patients with medulloblastoma or other CNS tumors.
Do I need to stop my current medications for this trial?
The trial requires that you stop taking corticosteroids at least one week before the first Nivolumab infusion. For other medications, the protocol does not specify, but you may need to stop certain anticancer therapies and investigational agents for a specified period before enrollment.
What evidence supports the effectiveness of the drugs Nivolumab, Methotrexate, and 5-Azacytidine for treating recurrent brain tumors?
Methotrexate has shown effectiveness in extending survival in patients with primary brain lymphomas, and it has been used in combination with other drugs to treat central nervous system lymphomas. Additionally, Methotrexate has been found to sensitize drug-resistant cancer cells to other treatments, potentially enhancing their effectiveness.12345
Is there any safety information about Methotrexate for humans?
Methotrexate has been used in combination with other drugs for treating rheumatoid arthritis, and in one study, no patients experienced any adverse effects when it was used with low-dose mizoribine. However, patients with rheumatoid arthritis using disease-modifying drugs like Methotrexate may have an increased risk of certain cancers, particularly lymphoproliferative disorders.678910
How is the drug combination of Nivolumab, Methotrexate, and 5-Azacytidine unique for treating recurrent brain tumors?
This drug combination is unique because it combines Nivolumab, an immunotherapy that helps the immune system attack cancer cells, with Methotrexate and 5-Azacytidine, which are chemotherapy drugs that work by stopping cancer cell growth. This approach is novel as it integrates both immune system activation and direct cancer cell inhibition, potentially offering a new strategy for treating recurrent brain tumors where standard treatments are limited.3451112
Research Team
Peter H. Yang, MD
Principal Investigator
The University of Texas Health Science Center, Houston
Eligibility Criteria
This trial is for people with recurrent brain tumors like medulloblastoma and ependymoma. Participants should have a tumor that can be measured, no prior immunotherapy, and adequate organ function. They must not have an active infection or another cancer, be pregnant, or have had recent surgery.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive intraventricular infusions of nivolumab plus 5-azacytidine or methotrexate for 12 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
Treatment Details
Interventions
- 5-Azacytidine
- Methotrexate
- Nivolumab
5-Azacytidine is already approved in United States, European Union for the following indications:
- Myelodysplastic syndromes (MDS)
- Acute myeloid leukemia (AML)
- Myelodysplastic syndromes (MDS)
- Acute myeloid leukemia (AML)
- Chronic myelomonocytic leukemia (CMML)
- Acute myeloid leukemia (AML)
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Who Is Running the Clinical Trial?
David Ilan Sandberg
Lead Sponsor
Peter H. Yang
Lead Sponsor