Rapid radiological response of leptomeningeal carcinosis and prolonged survival to encorafenib and binimetinib in BRAF-mutated melanoma.
Giacomo Corradi, Sara De Martino, Angela Rinaldi...
https://pubmed.ncbi.nlm.nih.gov/40439484Actively Recruiting
Phase 2
Age: 18Years +
All Genders
ID05026983
Phase II Study of Binimetinib and Encorafenib in Patients With Metastatic Melanoma and Brain or CNS Metastases
Led by M.D. Anderson Cancer Center · Updated on 2026-04-16
35
Participants Needed
1
Research Sites
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the effects of binimetinib and encorafenib in patients with melanoma that has spread to the central nervous system, including brain metastases and leptomeningeal disease. This phase II study focuses on patients with BRAF V600 mutation-positive melanoma to assess how this combination therapy may control tumor growth and improve outcomes such as progression-free survival and overall survival. The study also aims to understand the safety and immune effects of these drugs in the brain and blood. Participants receive oral encorafenib once daily and binimetinib twice daily in 28-day treatment cycles. These cycles continue as long as the disease does not progress and side effects remain manageable. After finishing treatment, patients have follow-up visits starting 30 days later and then every 12 weeks to monitor their health and disease status. The study evaluates responses in brain metastases, extracranial sites, and overall tumor control. During the trial, patients undergo regular assessments to track tumor progression and side effects, including imaging scans and questionnaires measuring cognitive function and symptoms related to brain tumors. Researchers also collect samples to study drug levels and immune responses in the cerebrospinal fluid and blood. Safety is closely monitored during treatment and for up to three years to observe any dose-limiting toxicities or adverse events. This comprehensive monitoring helps understand the impact of the therapy on disease and patient well-being.
CONDITIONS
Brief Title
Binimetinib and Encorafenib for the Treatment of Metastatic Melanoma and Central Nervous System Metastases
Who Can Participate
Age: 18Years +
All Genders
Eligibility Criteria
You may qualify if you...
- Able to provide written informed consent
- Age 18 years or older at the time of consent
- Histologically confirmed melanoma
- Presence of BRAFV600 mutation in tumor tissue confirmed by local testing
- For Cohort A: progressive CNS metastases including brain metastases and/or leptomeningeal disease
- For Cohort A: prior treatment with FDA-approved BRAF inhibitors with or without MEK inhibitors
- For Cohort A: prior immunotherapy or investigational agents allowed with a 14-day washout
- For Cohort B: BRAF V600 mutant melanoma patients naive to BRAF/MEK inhibitors with CNS metastases; prior immunotherapy allowed
- For patients with brain metastases without leptomeningeal disease: at least 1 progressing brain lesion between 0.5 cm and 3 cm measurable by MRI
- For patients with leptomeningeal disease: radiographic and/or cerebrospinal fluid cytology evidence
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- Steroid use allowed with dose limits and symptom stability
- Prior radiation therapy allowed with progression or new lesions; radiation completed at least 7 days prior for leptomeningeal disease
- No concurrent anti-cancer systemic therapies or intrathecal agents
- Adequate laboratory values for blood counts, liver and kidney function
- Female patients of childbearing potential must have negative pregnancy test and use contraception
- Male patients must use contraception
- Ability to comply with study visits and procedures
You will not qualify if you...
- Active infection within 7 days before starting study drug (except viral infections related to tumor)
- Use of live virus vaccines within 30 days before study drug; dead virus vaccines allowed
- Inability to swallow or retain study treatment
- Known HIV/AIDS infection
- Significant cardiovascular disease including recent heart attack, heart failure, low ejection fraction, serious arrhythmias, or prolonged QT interval
- Neuromuscular disorders like myopathies or muscular dystrophy
- Gastrointestinal conditions affecting drug absorption or history of pancreatitis
- Retinal vein occlusion or risk factors for it
- Use of strong cytochrome P450 3A4/5 inhibitors or inducers within 1 week before treatment
- Thromboembolic event within 12 weeks before treatment, except stable catheter-related events
- Evidence of hepatitis B or C infection, except cleared infections
- Pregnancy or breastfeeding or planning pregnancy during the study
- Other severe medical or psychiatric conditions that increase risk or interfere with study participation as judged by the investigator
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
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Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - Repeated 28-day cycles until disease progression or discontinuation
Participants receive encorafenib orally once daily and binimetinib orally twice daily in repeated 28-day cycles until disease progression or unacceptable toxicity.
Visits occur every 28 days during treatment cycles
Follow-up
Duration - Up to 3 years
After completing treatment, participants are followed up to monitor safety and disease status.
1 visit at 30 days after treatment, then visits every 12 weeks thereafter
Trial Site Locations
Total: 1 location
1
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Actively Recruiting
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Research Team
I
Isabella C Glitza, MD,PHD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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