Binimetinib and Encorafenib for the Treatment of Metastatic Melanoma and Central Nervous System Metastases

Recruiting now · Phase 2

Conditions studied: Clinical Stage IV Cutaneous Melanoma AJCC v8, Metastatic Melanoma, Pathologic Stage IV Cutaneous Melanoma AJCC v8

In brief

This phase II trial studies the effects of binimetinib and encorafenib in treating patients with melanoma that has spread to the central nervous system (metastases). Binimetinib and encorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving binimetinib and encorafenib may help control melanoma that has spread to the brain.

Key facts

Study ID: NCT05026983
Run by: M.D. Anderson Cancer Center
People needed: 35
Starts: 2021-12-27
Expected to finish: 2027-02-02
Last updated by the study team: 2026-04-16

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Able to provide written informed consent.
Age >= 18 years at the time of informed consent
Histologically confirmed diagnosis of melanoma
Presence of BRAFV600 mutation in tumor tissue previously determined by a local assay (including immunohistochemistry [IHC]) at any time prior to Screening or during Screening
Cohort A: BRAF V600 mutant melanoma patients with progressive central nervous system (CNS) metastases. This includes patients with parenchymal brain metastases and/or LMD
Cohort A: Prior therapy with Food and Drug Administration (FDA)-approved BRAF inhibitors (+/- MEK inhibitors) is required
No washout period is required
Cohort A: Prior therapy with immunotherapy or other investigational agents is allowed
Washout period of 14 days since last dose
Cohort B: BRAF V600 mutant melanoma patients who are treatment naive to BRAF/MEK inhibitors with CNS metastases, including LMD. Prior treatment with immunotherapy is permitted
For patients with parenchymal brain metastases (mets) without LMD
Metastatic disease to the brain with at least 1 progressing parenchymal brain lesion >= 0.5 cm and =< 3 cm, defined as a magnetic resonance imaging (MRI) contrast-enhancing lesion that may be accurately measured in at least 1 dimension
For patients with LMD
Patients must have investigator assessed radiographic and/or CSF cytological evidence of LMD
Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of =< 2
Patients may receive steroids to control symptoms related to CNS involvement
For patients with parenchymal brain metastases the dose must be =< 2 mg per 24 hours of dexamethasone (or the equivalent). Patient's symptoms should experience stability of neurological symptoms for at least 7 days, or on tapering dose of steroids. Physiologic replacement doses for adrenal insufficiency is allowed on this protocol
For patients with LMD: the dose must be =< 4 mg per 24 hours of dexamethasone (or the equivalent). Physiologic replacement doses for adrenal insufficiency is allowed on this protocol
Radiation therapy:
For patients with parenchymal brain mets: prior radiation therapy, including stereotactic (SRS) or whole brain radiation (WBXRT) is allowed, but patient must be progressing in or having at least 1 new CNS lesion. Prior SBRT to extracranial lesions is allowed. Washout to prior radiation 14 days.
For patients with LMD: Patients who have received radiation to brain and/or spine, including WBXRT, SRS, or SBRT, are eligible, but must have completed radiation treatment at least 7 days prior to the start of treatment.
Prior therapy with systemic immunotherapy or other investigational agents is allowed
Washout period of 14 days since last dose
Other cancer directed treatment:
Concurrent treatment with other anti-cancer systemic therapies is not allowed. No other concomitant intrathecal therapy with another agent will be allowed. For patients that have received other systemic therapies, the minimum wash out period is as follows:

You may not qualify if…

Evidence of active infection =< 7 days prior to initiation of study drug therapy (does not apply to viral infections that are presumed to be associated with the underlying tumor type required for study entry)
Use of non-oncology vaccines containing live virus for prevention of infectious diseases within 30 days of prior to study drug. Dead virus vaccines (e.g Flu) are allowed, even during treatment with study drug
Inability to swallow and retain study treatment
Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) even if fully immunocompetent on antiretroviral therapy (ART)
Impaired cardiovascular function or clinically significant cardiovascular disease including, but not limited to, the following:
History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) < 6 months prior to screening
Congestive heart failure requiring treatment (New York Heart Association grade >= 2)
A left ventricular ejection fraction (LVEF) < 50% as determined by multigated acquisition (MUGA) or echocardiogram (ECHO)
History or presence of clinically significant cardiac arrhythmias (including resting bradycardia, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia)
Baseline Fridericia's correction formula (QTcF) interval >= 480 msec. Can be repeated up to three times to confirm
Concurrent neuromuscular disorder (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
Impairment of gastrointestinal function or disease which may significantly alter the absorption of study treatment (e.g., uncontrolled nausea, vomiting or diarrhea; malabsorption syndrome; small bowel resection). Known history of acute or chronic pancreatitis
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes); history of retinal degenerative disease
Use of herbal supplements, medications or foods that are moderate or strong inhibitors or inducers of cytochrome P450 (CYP) 3A4/5 =< 1 week prior to the start of study treatment
History of a thromboembolic event < 12 weeks prior to starting study treatment. Examples of thromboembolic events include transient ischemia attack, cerebrovascular accident, deep vein thrombosis or pulmonary embolism. Catheter-related venous thrombosis is not considered a thromboembolic event for this trial even if < 12 weeks prior to starting study treatment. Note: Patients with either deep vein thrombosis or pulmonary emboli that do not result in hemodynamic instability are allowed to enroll as long as they are stable, asymptomatic and on stable anticoagulants for at least 2 weeks. Additionally, patients with thromboembolic events related to indwelling catheters or other procedures may be enrolled
Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
NOTE: Patients with laboratory evidence of cleared HBV or HCV infection may be enrolled
NOTE: Patients with no prior history of HBV infection who have been vaccinated against HBV and who have a positive antibody against hepatitis B surface antigen as the only evidence of prior exposure may enroll
Pregnancy or breastfeeding or patients who plan to become pregnant during the duration of the study
Other severe, acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study treatment administration or that may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient an inappropriate candidate for the study

Where it is running

M D Anderson Cancer Center — Houston, Texas, United States (enrolling)

Full record on ClinicalTrials.gov

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