Trametinib + Everolimus for Recurrent Brain Cancer
Trial Summary
What is the purpose of this trial?
This phase I trial studies the side effects and best dose of trametinib and everolimus in treating pediatric and young adult patients with gliomas that have come back (recurrent). Trametinib acts by targeting a protein in cells called MEK and disrupting tumor growth. Everolimus is a drug that may block another pathway in tumor cells that can help tumors grow. Giving trametinib and everolimus may work better to treat low and high grade gliomas compared to trametinib or everolimus alone.
Will I have to stop taking my current medications?
The trial requires participants to stop taking certain medications, including strong inducers or inhibitors of CYP3A4/5, some anti-convulsant drugs, and herbal preparations like St. John's wort, at least 7 days before enrolling. If you're taking any of these, you may need to stop or switch medications before joining the trial.
What data supports the effectiveness of the drug combination Trametinib and Everolimus for recurrent brain cancer?
Research shows that combining everolimus with other drugs targeting similar pathways can be effective in treating certain brain tumors, with some patients experiencing partial responses or stable disease. This suggests potential benefits of using everolimus in combination therapies for brain cancer.12345
What safety data exists for Trametinib and Everolimus in humans?
Everolimus has been studied for safety in children with epilepsy related to tuberous sclerosis, showing some promise but with limited evidence. Trametinib has been used in children with brain tumors, with side effects like skin issues, mouth sores, fever, and fatigue, especially when combined with other treatments.14678
How is the drug combination of Trametinib and Everolimus unique for treating recurrent brain cancer?
The combination of Trametinib and Everolimus is unique because it targets two different pathways involved in cancer growth: Trametinib inhibits the MEK pathway, while Everolimus inhibits the mTOR pathway. This dual approach may help overcome resistance that can develop with treatments targeting only one pathway.123910
Research Team
Sabine Mueller, MD, PhD, MAS
Principal Investigator
University of California, San Francisco
Eligibility Criteria
This trial is for pediatric and young adult patients with recurrent gliomas, including those with low grade (WHO I-II) or high grade (III-VI) tumors. It's open to participants who've had prior treatments and have stable neurological deficits. They must not be pregnant, agree to use contraception, and meet specific health criteria like adequate blood counts and organ function.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive a combination of trametinib and everolimus in a dose-escalation study, with treatment repeating every 28 days for up to 26 cycles
Follow-up
Participants are monitored for safety and effectiveness after treatment completion, with follow-ups at 30 days, every 3 months for 1 year, then every 6 months for 5 years
Treatment Details
Interventions
- Everolimus
- Trametinib
Everolimus is already approved in United States, European Union for the following indications:
- Advanced renal cell carcinoma
- Subependymal giant cell astrocytoma
- Progressive neuroendocrine tumors of pancreatic origin
- Advanced hormone receptor-positive, HER2-negative breast cancer
- Tuberous sclerosis complex-associated partial-onset seizures
- Subependymal giant cell astrocytoma
- Renal angiomyolipoma
- Tuberous sclerosis complex-associated partial-onset seizures
- Prevention of organ rejection in kidney transplant patients
Find a Clinic Near You
Who Is Running the Clinical Trial?
University of California, San Francisco
Lead Sponsor
Novartis Pharmaceuticals
Industry Sponsor
Dr. Vas Narasimhan
Novartis Pharmaceuticals
Chief Executive Officer since 2018
MD from Harvard Medical School
Dr. Shreeram Aradhye
Novartis Pharmaceuticals
Chief Medical Officer since 2021
MD
Pediatric Brain Tumor Foundation
Collaborator
The Lilabean Foundation for Pediatric Brain Cancer Research
Collaborator