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

RecruitingPhase 2

A Randomized Phase 2 Trial of Encorafenib + Binimetinib + Nivolumab vs Ipilimumab + Nivolumab in BRAF-V600 Mutant Melanoma With Brain Metastases

Who can join

Ages 18 and older · All sexes

Full eligibility 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

About the study

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.

What is being tested

Sponsor: SWOG Cancer Research Network · Participants: 112 · Started: Jan 6, 2021

Contact the study team

Official record on ClinicalTrials.gov — NCT04511013

Locations in the U.S.

AlabamaUniversity of Alabama at Birmingham Cancer Center, Birmingham
Thomas Hospital, Fairhope
Mobile Infirmary Medical Center, Mobile
AlaskaAlaska Breast Care and Surgery LLC, Anchorage
Alaska Oncology and Hematology LLC, Anchorage
Alaska Women's Cancer Care, Anchorage
Anchorage Associates in Radiation Medicine, Anchorage
Anchorage Oncology Centre, Anchorage
Anchorage Radiation Therapy Center, Anchorage
Katmai Oncology Group, Anchorage
Providence Alaska Medical Center, Anchorage
Fairbanks Memorial Hospital, Fairbanks
ArkansasMercy Hospital Fort Smith, Fort Smith
CaliforniaProvidence Saint Joseph Medical Center/Disney Family Cancer Center, Burbank
Epic Care-Dublin, Dublin
Bay Area Breast Surgeons Inc, Emeryville
Epic Care Partners in Cancer Care, Emeryville
UCLA / Jonsson Comprehensive Cancer Center, Los Angeles
Contra Costa Regional Medical Center, Martinez
Providence Queen of The Valley, Napa
Bay Area Tumor Institute, Oakland
Sharp Memorial Hospital, San Diego
Providence Medical Foundation - Santa Rosa, Santa Rosa
Providence Santa Rosa Memorial Hospital, Santa Rosa
Epic Care Cyberknife Center, Walnut Creek
ColoradoRocky Mountain Cancer Centers-Aurora, Aurora
University of Colorado Hospital, Aurora
Boulder Community Foothills Hospital, Boulder
Rocky Mountain Cancer Centers-Boulder, Boulder
Rocky Mountain Cancer Centers - Centennial, Centennial
Colorado Blood Cancer Institute, Denver
Presbyterian - Saint Lukes Medical Center - Health One, Denver
Rocky Mountain Cancer Centers-Midtown, Denver
Rocky Mountain Cancer Centers-Rose, Denver
The Women's Imaging Center, Denver
Mountain Blue Cancer Care Center - Swedish, Englewood
Rocky Mountain Cancer Centers - Swedish, Englewood
Swedish Medical Center, Englewood
The Melanoma and Skin Cancer Institute, Englewood
Rocky Mountain Cancer Centers-Lakewood, Lakewood
Rocky Mountain Cancer Centers-Littleton, Littleton
Rocky Mountain Cancer Centers-Sky Ridge, Lone Tree
Rocky Mountain Cancer Centers-Thornton, Thornton
FloridaOrlando Health Cancer Institute, Orlando
Moffitt Cancer Center, Tampa
Moffitt Cancer Center - McKinley Campus, Tampa
Moffitt Cancer Center-International Plaza, Tampa
IdahoSaint Alphonsus Cancer Care Center-Boise, Boise
Saint Luke's Cancer Institute - Boise, Boise
Saint Alphonsus Cancer Care Center-Caldwell, Caldwell
Kootenai Health - Coeur d'Alene, Coeur d'Alene
Walter Knox Memorial Hospital, Emmett
Saint Luke's Cancer Institute - Fruitland, Fruitland
Idaho Urologic Institute-Meridian, Meridian
Saint Luke's Cancer Institute - Meridian, Meridian
Saint Alphonsus Cancer Care Center-Nampa, Nampa
Saint Luke's Cancer Institute - Nampa, Nampa
Kootenai Clinic Cancer Services - Post Falls, Post Falls
Kootenai Cancer Clinic, Sandpoint
Saint Luke's Cancer Institute - Twin Falls, Twin Falls
IllinoisSaint Anthony's Health, Alton
Rush - Copley Medical Center, Aurora
Illinois CancerCare-Bloomington, Bloomington
Illinois CancerCare-Canton, Canton
Memorial Hospital of Carbondale, Carbondale
SIH Cancer Institute, Carterville
Illinois CancerCare-Carthage, Carthage
Centralia Oncology Clinic, Centralia
Saint Mary's Hospital, Centralia
Carle at The Riverfront, Danville
Cancer Care Specialists of Illinois - Decatur, Decatur
Decatur Memorial Hospital, Decatur
Illinois CancerCare-Dixon, Dixon
Carle Physician Group-Effingham, Effingham
Crossroads Cancer Center, Effingham
Illinois CancerCare-Eureka, Eureka
Illinois CancerCare-Galesburg, Galesburg
Western Illinois Cancer Treatment Center, Galesburg
Illinois CancerCare-Kewanee Clinic, Kewanee
Illinois CancerCare-Macomb, Macomb
Good Samaritan Regional Health Center, Mount Vernon
Cancer Care Center of O'Fallon, O'Fallon
Illinois CancerCare-Ottawa Clinic, Ottawa
Illinois CancerCare-Pekin, Pekin
Illinois CancerCare-Peoria, Peoria
Methodist Medical Center of Illinois, Peoria
Illinois CancerCare-Peru, Peru
Valley Radiation Oncology, Peru
Illinois CancerCare-Princeton, Princeton
Memorial Medical Center, Springfield
Southern Illinois University School of Medicine, Springfield
Springfield Clinic, Springfield
Carle Cancer Center, Urbana
The Carle Foundation Hospital, Urbana
Illinois CancerCare - Washington, Washington
Rush-Copley Healthcare Center, Yorkville
IndianaReid Health, Richmond
IowaMary Greeley Medical Center, Ames
McFarland Clinic - Ames, Ames
McFarland Clinic - Boone, Boone
Saint Anthony Regional Hospital, Carroll
Broadlawns Medical Center, Des Moines
Iowa Lutheran Hospital, Des Moines
Iowa Methodist Medical Center, Des Moines
Medical Oncology and Hematology Associates-Des Moines, Des Moines
McFarland Clinic - Trinity Cancer Center, Fort Dodge
Trinity Regional Medical Center, Fort Dodge
McFarland Clinic - Jefferson, Jefferson
McFarland Clinic - Marshalltown, Marshalltown
Methodist West Hospital, West Des Moines
KansasCentral Care Cancer Center - Garden City, Garden City
Central Care Cancer Center - Great Bend, Great Bend
KentuckyMercy Health - Paducah Medical Oncology and Hematology, Paducah
MichiganUniversity of Michigan Comprehensive Cancer Center, Ann Arbor
Bronson Battle Creek, Battle Creek
University of Michigan - Brighton Center for Specialty Care, Brighton
Helen DeVos Children's Hospital at Spectrum Health, Grand Rapids
Spectrum Health at Butterworth Campus, Grand Rapids
Trinity Health Grand Rapids Hospital, Grand Rapids
Ascension Borgess Cancer Center, Kalamazoo
Borgess Medical Center, Kalamazoo
Bronson Methodist Hospital, Kalamazoo
West Michigan Cancer Center, Kalamazoo
Trinity Health Muskegon Hospital, Muskegon
Lakeland Hospital Niles, Niles
Cancer and Hematology Centers of Western Michigan - Norton Shores, Norton Shores
Spectrum Health Reed City Hospital, Reed City
Lakeland Medical Center Saint Joseph, Saint Joseph
Marie Yeager Cancer Center, Saint Joseph
Munson Medical Center, Traverse City
University of Michigan Health - West, Wyoming
MinnesotaMinnesota Oncology - Burnsville, Burnsville
Cambridge Medical Center, Cambridge
Mercy Hospital, Coon Rapids
Fairview Southdale Hospital, Edina
Unity Hospital, Fridley
Fairview Clinics and Surgery Center Maple Grove, Maple Grove
Minnesota Oncology Hematology PA-Maplewood, Maplewood
Saint John's Hospital - Healtheast, Maplewood
Abbott-Northwestern Hospital, Minneapolis
Health Partners Inc, Minneapolis
Hennepin County Medical Center, Minneapolis
Monticello Cancer Center, Monticello
New Ulm Medical Center, New Ulm
Fairview Northland Medical Center, Princeton
North Memorial Medical Health Center, Robbinsdale
Park Nicollet Clinic - Saint Louis Park, Saint Louis Park
Regions Hospital, Saint Paul
United Hospital, Saint Paul
Saint Francis Regional Medical Center, Shakopee
Lakeview Hospital, Stillwater
Ridgeview Medical Center, Waconia
Rice Memorial Hospital, Willmar
Minnesota Oncology Hematology PA-Woodbury, Woodbury
Fairview Lakes Medical Center, Wyoming
MissouriSaint Louis Cancer and Breast Institute-Ballwin, Ballwin
Central Care Cancer Center - Bolivar, Bolivar
Cox Cancer Center Branson, Branson
Saint Francis Medical Center, Cape Girardeau
Southeast Cancer Center, Cape Girardeau
Parkland Health Center - Farmington, Farmington
Capital Region Southwest Campus, Jefferson City
Freeman Health System, Joplin
Mercy Hospital Joplin, Joplin
Delbert Day Cancer Institute at PCRMC, Rolla
Mercy Clinic-Rolla-Cancer and Hematology, Rolla
Heartland Regional Medical Center, Saint Joseph
Sainte Genevieve County Memorial Hospital, Sainte Genevieve
CoxHealth South Hospital, Springfield
Mercy Hospital Springfield, Springfield
Mercy Hospital Saint Louis, St Louis
Mercy Hospital South, St Louis
Missouri Baptist Medical Center, St Louis
Saint Louis Cancer and Breast Institute-South City, St Louis
Missouri Baptist Sullivan Hospital, Sullivan
Missouri Baptist Outpatient Center-Sunset Hills, Sunset Hills
Mercy Hospital Washington, Washington
MontanaCommunity Hospital of Anaconda, Anaconda
Billings Clinic Cancer Center, Billings
Bozeman Deaconess Hospital, Bozeman
Benefis Healthcare- Sletten Cancer Institute, Great Falls
Great Falls Clinic, Great Falls
Kalispell Regional Medical Center, Kalispell
Community Medical Hospital, Missoula
Saint Patrick Hospital - Community Hospital, Missoula
NebraskaCancer Partners of Nebraska - Pine Lake, Lincoln
Southeast Nebraska Cancer Center - 68th Street Place, Lincoln
North CarolinaWake Forest University at Clemmons, Clemmons
Southeastern Medical Oncology Center-Clinton, Clinton
Southeastern Medical Oncology Center-Goldsboro, Goldsboro
Southeastern Medical Oncology Center-Jacksonville, Jacksonville
Wake Forest Baptist Health - Hematology Oncology - Statesville, Statesville
Wake Forest Baptist Health - Wilkes Medical Center, Wilkesboro
Wake Forest University Health Sciences, Winston-Salem
OhioUHHS-Chagrin Highlands Medical Center, Beachwood
Indu and Raj Soin Medical Center, Beavercreek
Strecker Cancer Center-Belpre, Belpre
Saint Elizabeth Boardman Hospital, Boardman
Dayton Physicians LLC-Miami Valley South, Centerville
Geauga Hospital, Chardon
Adena Regional Medical Center, Chillicothe
Oncology Hematology Care Inc-Kenwood, Cincinnati
Case Western Reserve University, Cleveland
Columbus Oncology and Hematology Associates Inc, Columbus
Doctors Hospital, Columbus
Grant Medical Center, Columbus
Mount Carmel East Hospital, Columbus
Mount Carmel Health Center West, Columbus
Ohio State University Comprehensive Cancer Center, Columbus
Riverside Methodist Hospital, Columbus
The Mark H Zangmeister Center, Columbus
Dayton Physician LLC-Miami Valley Hospital North, Dayton
Delaware Health Center-Grady Cancer Center, Delaware
Grady Memorial Hospital, Delaware
Columbus Oncology and Hematology Associates, Dublin
Dublin Methodist Hospital, Dublin
Armes Family Cancer Center, Findlay
Blanchard Valley Hospital, Findlay
Orion Cancer Care, Findlay
Dayton Physicians LLC-Atrium, Franklin
Central Ohio Breast and Endocrine Surgery, Gahanna
Dayton Physicians LLC-Wayne, Greenville
Wayne Hospital, Greenville
Mount Carmel Grove City Hospital, Grove City
Zangmeister Center Grove City, Grove City
Greater Dayton Cancer Center, Kettering
Kettering Medical Center, Kettering
Fairfield Medical Center, Lancaster
Saint Rita's Medical Center, Lima
OhioHealth Mansfield Hospital, Mansfield
Marietta Memorial Hospital, Marietta
OhioHealth Marion General Hospital, Marion
UH Seidman Cancer Center at Southwest General Hospital, Middleburg Heights
Knox Community Hospital, Mount Vernon
Mount Carmel New Albany Surgical Hospital, New Albany
Licking Memorial Hospital, Newark
Newark Radiation Oncology, Newark
University Hospitals Parma Medical Center, Parma
Mercy Health Perrysburg Cancer Center, Perrysburg
Southern Ohio Medical Center, Portsmouth
University Hospitals Portage Medical Center, Ravenna
UH Seidman Cancer Center at Firelands Regional Medical Center, Sandusky
Springfield Regional Cancer Center, Springfield
Springfield Regional Medical Center, Springfield
Mercy Health - Saint Anne Hospital, Toledo
Saint Vincent Mercy Medical Center, Toledo
Dayton Physicians LLC - Troy, Troy
University Hospitals Sharon Health Center, Wadsworth
Saint Joseph Warren Hospital, Warren
Saint Ann's Hospital, Westerville
UH Seidman Cancer Center at Saint John Medical Center, Westlake
Saint Elizabeth Youngstown Hospital, Youngstown
Genesis Healthcare System Cancer Care Center, Zanesville
OklahomaMercy Hospital Oklahoma City, Oklahoma City
University of Oklahoma Health Sciences Center, Oklahoma City
OregonSaint Alphonsus Medical Center-Baker City, Baker City
Saint Charles Health System, Bend
Clackamas Radiation Oncology Center, Clackamas
Providence Cancer Institute Clackamas Clinic, Clackamas
Bay Area Hospital, Coos Bay
Providence Newberg Medical Center, Newberg
Saint Alphonsus Medical Center-Ontario, Ontario
Providence Willamette Falls Medical Center, Oregon City
Providence Portland Medical Center, Portland
Providence Saint Vincent Medical Center, Portland
Saint Charles Health System-Redmond, Redmond
PennsylvaniaUniversity of Pittsburgh Cancer Institute (UPCI), Pittsburgh
UtahHuntsman Cancer Institute/University of Utah, Salt Lake City
WashingtonProvidence Regional Cancer System-Aberdeen, Aberdeen
PeaceHealth Saint Joseph Medical Center, Bellingham
Providence Regional Cancer System-Centralia, Centralia
Swedish Cancer Institute-Edmonds, Edmonds
Providence Regional Cancer Partnership, Everett
Swedish Cancer Institute-Issaquah, Issaquah
Kadlec Clinic Hematology and Oncology, Kennewick
Providence Regional Cancer System-Lacey, Lacey
PeaceHealth Saint John Medical Center, Longview
Jefferson Healthcare, Port Townsend
Swedish Medical Center-Ballard Campus, Seattle
Swedish Medical Center-Cherry Hill, Seattle
Swedish Medical Center-First Hill, Seattle
PeaceHealth United General Medical Center, Sedro-Woolley
Providence Regional Cancer System-Shelton, Shelton
PeaceHealth Southwest Medical Center, Vancouver
Providence Saint Mary Regional Cancer Center, Walla Walla
Providence Regional Cancer System-Yelm, Yelm
WisconsinLanglade Hospital and Cancer Center, Antigo
Marshfield Medical Center-EC Cancer Center, Eau Claire
Gundersen Lutheran Medical Center, La Crosse
University of Wisconsin Carbone Cancer Center, Madison
Marshfield Medical Center-Marshfield, Marshfield
Aspirus Medford Hospital, Medford
Marshfield Clinic-Minocqua Center, Minocqua
Cancer Center of Western Wisconsin, New Richmond
Marshfield Medical Center-Rice Lake, Rice Lake
Ascension Saint Michael's Hospital, Stevens Point
Marshfield Medical Center-River Region at Stevens Point, Stevens Point
Aspirus Regional Cancer Center, Wausau
Marshfield Medical Center - Weston, Weston
Aspirus Cancer Care - Wisconsin Rapids, Wisconsin Rapids
WyomingCheyenne Regional Medical Center-West, Cheyenne
Billings Clinic-Cody, Cody
Welch Cancer Center, Sheridan

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.