FORTE
Clinical Trial plixorafenib
A trial targeting tumors with specific BRAF gene alterations that cause uncontrolled cell growth.
About the Trial
The objective of this trial is to determine how effective plixorafenib is for treating tumor types with specific BRAF alterations. The trial will also look at the safety and pharmacokinetics (how the drug is metabolized or processed in the body) of plixorafenib.
In the trial, plixorafenib is taken daily, orally in tablet form.
Some patients will take plixorafenib with another drug called cobicistat, which increases the level of plixorafenib in the blood.
Science
Targeting BRAF alterations as a cancer treatment
What is BRAF and why is it important?
BRAF proteins are large molecules that work with other proteins to relay a signal telling cells that it is time to grow and divide. Changes, or alterations, to the BRAF gene can cause the BRAF protein to keep this signal permanently on, meaning that affected cells may multiply uncontrollably and possibly form a cancerous tumor.
Tell me more about plixorafenib
Plixorafenib (sometimes also called FORE8394 or PLX-8394) inhibits BRAF signaling in such a way that it appears effective (in animal models of cancer, and in human trials) in the treatment of tumors driven by various types of BRAF alterations.
Plixorafenib is specifically designed to block the signaling of the altered protein in cancer cells and may slow the growth of tumors with specific BRAF alterations.
Study Eligibility
To be eligible for this study, you must meet certain criteria, including but not limited to the following:
- You have an advanced solid or central nervous system (CNS) tumor with a BRAF alteration confirmed by genetic analysis/testing.
- Your cancer has persisted despite prior therapy or is considered incurable using standard therapies.
- Your cancer is measurable on medical imaging scans such as computed tomography, or CT, and magnetic resonance imaging, or MRI.
- You can care for most of your own personal needs, requiring minimal assistance.
- You have adequate blood counts and kidney and liver function by routine laboratory tests.
- You must be 10 years or older and be at least 30 kg (65 lbs).
- You do not have active liver disease from any cause, including positive screening for hepatitis B or C.
- If you have a history of clinically significant cardiac disease or congestive heart failure, you may not be eligible for this study. Your doctor will explain this criteria.
Trial Details
What are my responsibilities if I enroll in this study?
- You will take plixorafenib with cobicistat by mouth, as directed by your doctor.
- The study will involve a weekly visit to a study doctor for the first six weeks, every other week for the next six weeks, and then once every 3 weeks after that. After one year on study, the visits may decrease in frequency.
Measurements/tests that may be taken under a specific schedule include:
- Because this is an investigational study of plixorafenib, measurements will have to be taken during the clinical trial throughout the time you are enrolled.
- You will see your doctor for what is called a screening visit. At this visit (which may take place over several days) your doctor will perform tests to confirm if you are eligible for the study. Some of these tests include a physical examination, blood tests, radiology evaluations (CT, MRI, or photographs to measure your disease), and may include a biopsy of your tumor.
- Vital signs and physical examination, blood tests, tumor biopsies, and radiology evaluations will be performed while you are receiving treatment in the study.
Frequently Asked Questions
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Typically, participants continue to see their usual healthcare providers while enrolled in a clinical trial. Although most clinical studies provide participants with medical products or interventions related to the illness or condition being studied, they do not provide extended or complete health care.
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The study doctor and their team will be responsible for monitoring your progress during the trial.
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You will receive treatment as long as you are tolerating it and any side effects may be managed and your disease has not worsened. You may then be followed for your disease course after completion of treatment. You may withdraw from a part of the study or the study as a whole at any time or if your physician considers it in your best interest.
The reasons that you may discontinue or be withdrawn from the study treatment include, but are not limited to, side effects, worsening of your cancer, patient request, study doctor decision, protocol violation, patient noncompliance, and study termination by the sponsor or Institutional Review Board/ Independent Ethics Committee.
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In previous plixorafenib clinical trials, the most common adverse events (experienced by at least 10% of subjects) were fatigue, nausea, diarrhea, vomiting, headache, and increases in some test results, such as levels of liver enzymes (alanine aminotransferase, aspartate aminotransferase) and/ or bilirubin, that help measure liver function, including some events that may be considered serious and related to plixorafenib/cobicistat. There may be unknown side effects.
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If your cancer should worsen or progress, your treatment may be discontinued, in discussion between you and your physician.
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Your physician and treatment team will evaluate your current medications to determine if any will interfere with receiving plixorafenib and determine a plan for you.
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Reimbursement for travel is available; this will be determined at your treatment center.
Learn More
To learn more about centers participating in the FORTE clinical trial please visit clinicaltrials.gov
References
- Mercer, K., et al. Raf proteins and cancer: B-Raf is identified as a mutational target. Biochim Biophys Acta. 2003 Jun 5;1653(1):25-40. doi: 10.1016/s0304-419x(03)00016-7.
- De la Fuente MI, et al. Safety and efficacy of the novel BRAF inhibitor FORE8394 in patients with advanced solid and CNS tumors: Results from a phase 1/2a study. J Clin Oncology. 2023;41(16_suppl): Abstract 3006. Available at: https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.3006.
- Yao, Z., et al. RAF inhibitor PLX8394 selectively disrupts BRAF dimers and RAS- independent BRAF-mutant-driven signaling. Nature medicine 25.2 (2019): 284-291.
- Fore Biotherapeutics. A Study to Assess the Efficacy and Safety of FORE8394 in Participants With Cancer Harboring BRAF Alterations. Available at: https://clinicaltrials.gov/study/NCT05503797.