Comparing two treatment combinations for melanoma with brain metastases
Official title: A Randomized Phase 2 Trial of Encorafenib + Binimetinib + Nivolumab vs Ipilimumab + Nivolumab in BRAF-V600 Mutant Melanoma With Brain Metastases
Run by SWOG Cancer Research Network · NCT04511013 · Data updated 2026-11-12
This study is testing two different treatment combinations for patients with melanoma that has spread to the brain to see which one helps them live longer without the disease getting worse.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Ages | 18 Years and up |
| Sex | All |
| Enrollment | 112 (estimated) |
| Sponsor | SWOG Cancer Research Network Research network |
| Drugs / interventions | infliximab, adalimumab, ipilimumab, nivolumab, binimetinib, radiation, methotrexate, prednisone, immunotherapy |
| Locations | 331 sites (Birmingham, Alabama and 330 other locations) |
| Status | Recruiting |
| Started | January 6, 2021 |
| Main results expected | June 30, 2027 |
| Study ends | June 30, 2027 |
| Registry record updated | September 15, 2026 |
| Trial ID | NCT04511013 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Ideal candidates are individuals with histologically confirmed BRAF-V600 mutant melanoma that has metastasized to the brain and has at least one measurable brain metastasis.
✕Probably not a fit
Patients with uveal melanoma or those who have had prior radiation therapy that has not resulted in measurable progression may not benefit from this study.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This phase II trial evaluates the effectiveness of a combination of encorafenib, binimetinib, and nivolumab against a combination of ipilimumab and nivolumab in patients with BRAF-V600 mutant melanoma that has spread to the brain. The primary goal is to compare progression-free survival between the two treatment groups. Secondary objectives include assessing overall survival, response rates, and the toxicity profiles of each treatment regimen. Additionally, the study aims to bank biological samples for future research.
Why it matters
Potential benefit: If successful, this study could provide a more effective treatment option for patients with advanced melanoma that has metastasized to the brain.
How similar studies have gone: Other studies have shown promising results with similar combination therapies in melanoma, indicating potential for success in this approach.
Who can join: the full rules
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 Exclusion Criteria: * 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's running
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University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States Recruiting -
Thomas Hospital
Fairhope, Alabama, United States Recruiting -
Mobile Infirmary Medical Center
Mobile, Alabama, United States Recruiting -
Anchorage Associates in Radiation Medicine
Anchorage, Alaska, United States Recruiting -
Anchorage Radiation Therapy Center
Anchorage, Alaska, United States Recruiting -
Alaska Breast Care and Surgery LLC
Anchorage, Alaska, United States Recruiting
Show 44 more locations
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Alaska Oncology and Hematology LLC
Anchorage, Alaska, United States Recruiting -
Alaska Women's Cancer Care
Anchorage, Alaska, United States Recruiting -
Anchorage Oncology Centre
Anchorage, Alaska, United States Recruiting -
Katmai Oncology Group
Anchorage, Alaska, United States Recruiting -
Providence Alaska Medical Center
Anchorage, Alaska, United States Recruiting -
Fairbanks Memorial Hospital
Fairbanks, Alaska, United States Recruiting -
Mercy Hospital Fort Smith
Fort Smith, Arkansas, United States Recruiting -
Providence Saint Joseph Medical Center/Disney Family Cancer Center
Burbank, California, United States Recruiting -
Epic Care-Dublin
Dublin, California, United States Recruiting -
Bay Area Breast Surgeons Inc
Emeryville, California, United States Recruiting -
Epic Care Partners in Cancer Care
Emeryville, California, United States Recruiting -
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, United States Recruiting -
Contra Costa Regional Medical Center
Martinez, California, United States Recruiting -
Providence Queen of The Valley
Napa, California, United States Recruiting -
Bay Area Tumor Institute
Oakland, California, United States Recruiting -
Sharp Memorial Hospital
San Diego, California, United States Recruiting -
Providence Medical Foundation - Santa Rosa
Santa Rosa, California, United States Recruiting -
Providence Santa Rosa Memorial Hospital
Santa Rosa, California, United States Recruiting -
Epic Care Cyberknife Center
Walnut Creek, California, United States Recruiting -
Rocky Mountain Cancer Centers-Aurora
Aurora, Colorado, United States Recruiting -
University of Colorado Hospital
Aurora, Colorado, United States Recruiting -
Boulder Community Foothills Hospital
Boulder, Colorado, United States Recruiting -
Rocky Mountain Cancer Centers-Boulder
Boulder, Colorado, United States Recruiting -
Rocky Mountain Cancer Centers - Centennial
Centennial, Colorado, United States Recruiting -
The Women's Imaging Center
Denver, Colorado, United States Recruiting -
Colorado Blood Cancer Institute
Denver, Colorado, United States Recruiting -
Presbyterian - Saint Lukes Medical Center - Health One
Denver, Colorado, United States Recruiting -
Rocky Mountain Cancer Centers-Midtown
Denver, Colorado, United States Recruiting -
Rocky Mountain Cancer Centers-Rose
Denver, Colorado, United States Recruiting -
Mountain Blue Cancer Care Center - Swedish
Englewood, Colorado, United States Recruiting -
Rocky Mountain Cancer Centers - Swedish
Englewood, Colorado, United States Recruiting -
Swedish Medical Center
Englewood, Colorado, United States Recruiting -
The Melanoma and Skin Cancer Institute
Englewood, Colorado, United States Recruiting -
Rocky Mountain Cancer Centers-Lakewood
Lakewood, Colorado, United States Recruiting -
Rocky Mountain Cancer Centers-Littleton
Littleton, Colorado, United States Recruiting -
Rocky Mountain Cancer Centers-Sky Ridge
Lone Tree, Colorado, United States Recruiting -
Rocky Mountain Cancer Centers-Thornton
Thornton, Colorado, United States Recruiting -
Orlando Health Cancer Institute
Orlando, Florida, United States Recruiting -
Moffitt Cancer Center-International Plaza
Tampa, Florida, United States Recruiting -
Moffitt Cancer Center - McKinley Campus
Tampa, Florida, United States Recruiting -
Moffitt Cancer Center
Tampa, Florida, United States Recruiting -
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, United States Recruiting -
Saint Luke's Cancer Institute - Boise
Boise, Idaho, United States Recruiting -
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, United States Recruiting
+281 more sites. See ClinicalTrials.gov for the full list.
Study contacts
- Principal investigator: Zeynep Eroglu — SWOG Cancer Research Network
- Study coordinator: Catrina Mireles
- Email: cmireles@swog.org
- Phone: 2106148808
Similar studies
Other studies for the same condition or treatment. Recruiting studies are listed first.
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Combining immunotherapy with prednisone and sirolimus for kidney transplant recipients with advanced skin cancer
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Natural Killer Cell Therapy and Temozolomide for Stage IV Melanoma with Brain Metastasis
This study is testing a new treatment combining special immune cells and a cancer drug to see if it helps people with advanced melanoma that has spread to the brain.
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Treatment of metastatic melanoma with binimetinib and encorafenib
This study is testing if a combination of two medications can help people with a specific type of melanoma that has spread to the brain feel better and live longer.
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30-minute cycling immediately before nivolumab and ipilimumab for metastatic melanoma
This trial will test whether a 30-minute cycling session immediately before nivolumab plus ipilimumab boosts immune activity and improves outcomes for people with metastatic melanoma.
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This tests whether using a ctDNA blood test to guide adding ipilimumab for adults with advanced or metastatic melanoma on nivolumab and relatlimab leads to longer progression-free survival.
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.