A Study to Compare the Administration of Encorafenib + Binimetinib + Nivolumab Versus Ipilimumab + Nivolumab in BRAF-V600 Mutant Melanoma With Brain Metastases

Recruiting now · Phase 2

Conditions studied: Acral Lentiginous Melanoma, Clinical Stage IV Cutaneous Melanoma AJCC v8, Metastatic Cutaneous Melanoma, Metastatic Malignant Neoplasm in the Brain, Metastatic Melanoma, Metastatic Mucosal Melanoma, Pathologic Stage IV Cutaneous Melanoma AJCC v8

In brief

This phase II trial compares the effect of encorafenib, binimetinib, and nivolumab versus ipilimumab and nivolumab in treating patients with BRAF- V600 mutant melanoma that has spread to the brain (brain metastases). Encorafenib and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Ipilimumab and nivolumab are monoclonal antibodies that may interfere with the ability of tumor cells to grow and spread. This trial aims to find out which approach is more effective in shrinking and controlling brain metastases from melanoma.

Key facts

Study ID

NCT04511013

Run by

SWOG Cancer Research Network

People needed

112

Starts

2021-01-06

Expected to finish

2027-06-30

Last updated by the study team

2025-09-11

Who can join

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

You may qualify if…

• Participants must have histologically and pathologically confirmed melanoma that has metastasized to the brain
• Any primary (cutaneous, acral/mucosal, etc) or unknown origin are permitted, except that participants with uveal primary are not eligible
• Participants must have BRAF-V600 mutant melanoma documented by a Clinical Laboratory Improvement Act (CLIA)-certified laboratory
• All participants must have an magnetic resonance imaging (MRI) of the brain within 28 days prior to registration and must have central nervous system metastases with at least one measurable brain metastasis >= 0.5 cm in size (per modified RECIST 1.1) that has not been irradiated, or progressed (in the opinion of the treating physician) after prior radiation therapy. Participating sites MUST use MRI slice thickness of =< 1.5 mm and are recommended to adhere to the 'minimum' Brain Tumor Imaging Protocol for Clinical Trials in Brain Metastases (BTIP-BM) compliant MRI acquisition protocol. Computed tomography (CT) of the head cannot substitute for brain MRI. (NOTE: All central nervous system [CNS] disease must be documented on BOTH the Brain Metastases Baseline Tumor Assessment Form, using modified RECIST, and the Baseline Tumor Assessment Form [RECIST 1.1] using RECIST 1.1.)
• Participants may have measurable or non-measurable extracranial disease. All measurable disease must be assessed within 28 days prior to randomization; all non-measurable disease must be assessed within 42 days prior to randomization. Please note, while any extracranial disease will also be assessed and followed, participants are NOT required to have extracranial disease for randomization. NOTE: All disease must be assessed and documented on the Baseline Tumor Assessment Form (RECIST 1.1). CNS disease must be documented on BOTH the Brain Metastases Baseline Tumor Assessment Form, using modified RECIST, and the Baseline Tumor Assessment Form (RECIST 1.1) using RECIST 1.1
• Participants may have leptomeningeal disease
• Participants may be receiving corticosteroids for brain metastases at a dose of up to 8 mg of dexamethasone per day. The dose must not have exceeded 8 mg per day for at least 7 days prior to randomization
• Participants must have Zubrod performance status =< 2
• Participants must have complete history and physical examination within 28 days prior to randomization
• Participants must be able to swallow and retain pills
• Hemoglobin >= 8.0 g/dL (within 28 days prior to randomization)
• Absolute neutrophil count >= 1,500/mcL (within 28 days prior to randomization)
• Platelets >= 75,000/mcL (within 28 days prior to randomization)
• Total bilirubin =< 1.5 institutional upper limit of normal (ULN) (within 28 days prior to randomization)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional ULN (in participants with liver metastases =< 5 x ULN) (within 28 days prior to randomization)
• Creatinine =< 2.0 institutional ULN (within 28 days prior to randomization)
• Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better
• Participants with a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Participants with known human immunodeficiency virus (HIV)-infection are eligible providing they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 90 days prior to randomization
• Participants with a known history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment must have an undetectable HCV viral load prior to randomization
• Participants must agree to participate in image banking. Images must be submitted via the Triad System
• Participants must be offered the opportunity to participate in specimen and blood collections
• Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
• As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

You may not qualify if…

• Participants must not have received prior systemic therapy for metastatic disease. Prior systemic therapy received only in the neoadjuvant and/or adjuvant setting (e.g., BRAF/MEK inhibitor therapy, anti-PD-1 therapy or anti-CTLA4 therapy, alfa-interferon, etc.) is permitted. If patients received prior neoadjuvant/adjuvant therapy, they must have had eventual disease relapse prior to randomization
• Participants must not have had prior radiation therapy within 7 days prior to randomization
• Participants must not be planning to require any additional form of systemic anti-tumor therapy for melanoma while on protocol treatment
• Participants must not be planning to use hormonal contraceptives
• Participants must not have a serious active infection requiring systemic therapy at time of randomization in the opinion of the treating physician
• Participants must not have active autoimmune disease that has required treatment in the past 6 months with use of biologic disease modifying agents (.e.g. infliximab, adalimumab). Patients on non-biologic disease modifying agents (e.g. methotrexate) or patients on corticosteroids =< 10 mg prednisone daily or equivalent (to treat auto-immune disease), or on replacement therapy (e.g., thyroxine, insulin) are eligible if deemed in the best interest of the patient by treating physician
• Participants must not have had grade 3 or 4 immune-related adverse events on ipilimumab or nivolumab that required more than 12 weeks of immune suppression with corticosteroids
• Participants must not have had adverse events related to encorafenib and/or binimetinib specifically, that required discontinuation of one or both drugs. (Please note this does not apply to other BRAF/MEK inhibitor drugs.)
• Participants must not be pregnant or nursing. Women/men of reproductive potential must have agreed to use an effective method of contraception. (NOTE: Patients must agree to not use hormonal contraceptives, as encorafenib can result in decreased concentration and loss of efficacy.) A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate participant chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures

Where it is running

• University of Alabama at Birmingham Cancer Center — Birmingham, Alabama, United States (enrolling)
• Mobile Infirmary Medical Center — Mobile, Alabama, United States (enrolling)
• Anchorage Associates in Radiation Medicine — Anchorage, Alaska, United States (enrolling)
• Thomas Hospital — Fairhope, Alabama, United States (enrolling)
• Alaska Breast Care and Surgery LLC — Anchorage, Alaska, United States (enrolling)
• Alaska Oncology and Hematology LLC — Anchorage, Alaska, United States (enrolling)
• Alaska Women's Cancer Care — Anchorage, Alaska, United States (enrolling)
• Anchorage Oncology Centre — Anchorage, Alaska, United States (enrolling)
• Anchorage Radiation Therapy Center — Anchorage, Alaska, United States (enrolling)
• Providence Alaska Medical Center — Anchorage, Alaska, United States (enrolling)
• Fairbanks Memorial Hospital — Fairbanks, Alaska, United States (enrolling)
• Mercy Hospital Fort Smith — Fort Smith, Arkansas, United States (enrolling)
• Providence Saint Joseph Medical Center/Disney Family Cancer Center — Burbank, California, United States (enrolling)
• Epic Care-Dublin — Dublin, California, United States (enrolling)
• Bay Area Breast Surgeons Inc — Emeryville, California, United States (enrolling)
• Epic Care Partners in Cancer Care — Emeryville, California, United States (enrolling)
• UCLA / Jonsson Comprehensive Cancer Center — Los Angeles, California, United States (enrolling)
• Contra Costa Regional Medical Center — Martinez, California, United States (enrolling)
• Providence Queen of The Valley — Napa, California, United States (enrolling)
• Katmai Oncology Group — Anchorage, Alaska, United States (enrolling)
• Bay Area Tumor Institute — Oakland, California, United States (enrolling)
• Sharp Memorial Hospital — San Diego, California, United States (enrolling)
• Providence Medical Foundation - Santa Rosa — Santa Rosa, California, United States (enrolling)
• Providence Santa Rosa Memorial Hospital — Santa Rosa, California, United States (enrolling)
• Epic Care Cyberknife Center — Walnut Creek, California, United States (enrolling)

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.