AzTrials
AzTrials

Clinical Stage IV Cutaneous Melanoma AJCC v8Phase 2NCT04527549

Testing Dabrafenib and Trametinib With or Without Hydroxychloroquine in Stage IIIC or IV BRAF V600E/K Melanoma

A Phase 2 study testing Dabrafenib mesylate, Hydroxychloroquine and Trametinib dimethyl sulfoxide in people with Clinical Stage IV Cutaneous Melanoma AJCC v8 and Locally Advanced Melanoma, run by ECOG-ACRIN Cancer Research Group at 199 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This phase II trial investigates how well adding hydroxychloroquine to the standard treatment of dabrafenib and trametinib works to overcome resistance and delay disease progression in treating patients with stage IIIC or IV BRAF V600E/K melanoma. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Dabrafenib mesylate, Hydroxychloroquine and Trametinib dimethyl sulfoxide
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
5 participants
Where
199 sitesUnited States
Study dates
1 Jun 2021to 8 Jan 2024
Phase
Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient must have locally advanced unresectable stage IIIC or stage IV melanoma
  • Patient must have BRAF V600E or BRAF V600K tumor genotype based on a Clinical Laboratory Improvement Act (CLIA) approved assay
  • Patient must have serum LDH > Upper limit of normal per institution standards
  • Patient must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Baseline measurements of sites of disease must be obtained within 3 weeks prior to study randomization
  • Patient must have been treated with prior immune checkpoint inhibitor therapy (anti PD-1 antibody, anti-CTLA-4 antibody or a combination regimen including either or both agents) either in the adjuvant or metastatic setting. Patient may have received investigational agents in combination with standard therapy, as long as it was adhering to the timeframes below
  • Patient must have discontinued active immunotherapy (IL-2, interferon, anti-CTLA-4 antibody, anti-PD-1 antibody etc.) or chemotherapy at least 4 weeks prior to randomization
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  • Patient must have discontinued any oral targeted therapy at least 2 weeks prior to randomization
  • Patient may have been treated with prior adjuvant therapy including combined BRAF and MEK inhibitor therapy. Patients will be eligible if they tolerated this therapy and did not discontinue the therapy due to toxicity AND >= 6 months have elapsed since the end of adjuvant BRAF and MEK inhibition.
  • Patient may have been treated with prior chemotherapy or radiation therapy
  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • All females of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy.
  • Women of childbearing potential and sexually active males must not expect to conceive or father children by using accepted and effective method(s) of contraception or abstaining from sexual intercourse for the duration of their participation in the study and for 4 months after the last dose of protocol treatment
  • Patient must have recovered from clinically significant reversible toxicities from previous treatment prior to randomization. Abnormal laboratory values may be grade 1, as long as they meet the eligibility criteria for organ and marrow function
  • Patient must be able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
  • Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
  • Absolute neutrophil count >= 1,500/mcL (obtained =< 14 days prior to protocol randomization)
  • Platelets >= 100,000/mcL (obtained =< 14 days prior to protocol randomization)
  • Total bilirubin =< institutional upper limit of normal (ULN) (obtained =< 14 days prior to protocol randomization)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x institutional ULN (obtained =< 14 days prior to protocol randomization)
  • Creatinine =< 1.5 x institutional ULN (obtained =< 14 days prior to protocol randomization)
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patient with asymptomatic new or progressive brain metastases (active brain metastases) are eligible if the treating physician determines that CNS specific treatment is not required
  • NOTE: Patient with treated brain metastases are eligible. No brain imaging is required, however, 1 week must elapse after gamma knife therapy. Patient treated with whole brain radiation that have been stable for 2 months are eligible. Patient are excluded if they have leptomeningeal disease or metastases causing spinal cord compression that are symptomatic or untreated or not stable (documented by imaging) for at least 3 months or requiring corticosteroids. Patients on a stable dose of corticosteroids for at least 1 month or who have been off of corticosteroids for at least 1 week are eligible

Who cannot join

  • Receiving any other investigational anticancer therapy during the period on study or the 4 weeks prior to randomization
  • Patients received BRAF and MEK inhibitor therapy in the metastatic setting
  • Patients who are experiencing an objective partial response to immunotherapy at the time of study enrollment
  • Pregnant or breast-feeding; due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • A history of interstitial lung disease (ILD) or chronic pneumonitis
  • NOTE: If there is radiographic evidence of ILD that is clinically insignificant and asymptomatic, the patient would be eligible
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  • Porphyria or psoriasis due to risk of disease exacerbation unless the disease is well controlled and they are under the care of a specialist for the disorder who agrees to monitor the patient for exacerbations
  • Previously documented retinal vein occlusion
  • A history or evidence of increased cardiovascular risk including:
  • Left ventricular ejection fraction (LVEF) < institutional lower limit of normal measured within 14 days prior to randomization
  • A QT interval corrected for heart rate using the Bazett's formula >= 480 msec
  • Current clinically significant uncontrolled arrhythmias. Exception: Patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible
  • Acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization
  • Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram unless a cardiologist concludes the valve abnormality is not clinically significant. Patients with grade 1 abnormalities (i.e., mild regurgitation/stenosis) are eligible
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • Serious concurrent infection or medical illness, including psychiatric disorders, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety
  • Receiving concurrent therapy for their tumor (i.e. chemotherapeutics or investigational agents). Radiotherapy delivered to palliate pain is allowed as long as it is not targeting a lesion that meets RECIST criteria for progression. Radiation therapy to the surgical bed with gamma knife radiotherapy while on treatment during the first cycle is allowed for small volume surgically resected brain metastases. Gamma knife radiotherapy for known active, asymptomatic small volume central nervous system (CNS) lesions may be performed during the first cycle while on study. Radiotherapy for new CNS lesions identified beyond the first cycle is not allowed on study
  • Immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study drug, or excipients or to dimethyl sulfoxide (DMSO)
  • Prior cytochrome P450 enzyme -inducing anticonvulsant drugs (extended-interval aminoglycoside dosing [EIADs]) (i.e. phenytoin, carbamazepine, phenobarbital, primidone or oxcarbazepine) within 4 weeks prior to randomization
  • Current use of a prohibited medication described in the protocol due to potential drug-drug interaction

Trial locations and contacts

199 sites in 1 country.

199 sites in 1 country

United States199 sites

  • Providence Regional Cancer System-Aberdeen

    Aberdeen, Washington, 98520

  • Saint Anthony's Health

    Alton, Illinois, 62002

  • Mary Greeley Medical Center

    Ames, Iowa, 50010

  • McFarland Clinic PC - Ames

    Ames, Iowa, 50010

  • Anchorage Associates in Radiation Medicine

    Anchorage, Alaska, 98508

  • Anchorage Radiation Therapy Center

    Anchorage, Alaska, 99504

  • Alaska Breast Care and Surgery LLC

    Anchorage, Alaska, 99508

  • Alaska Oncology and Hematology LLC

    Anchorage, Alaska, 99508

  • Alaska Women's Cancer Care

    Anchorage, Alaska, 99508

  • Anchorage Oncology Centre

    Anchorage, Alaska, 99508

  • Katmai Oncology Group

    Anchorage, Alaska, 99508

  • Providence Alaska Medical Center

    Anchorage, Alaska, 99508

  • Mission Hope Medical Oncology - Arroyo Grande

    Arroyo Grande, California, 93420

  • Rush - Copley Medical Center

    Aurora, Illinois, 60504

  • UM Sylvester Comprehensive Cancer Center at Aventura

    Aventura, Florida, 33180

  • Saint Louis Cancer and Breast Institute-Ballwin

    Ballwin, Missouri, 63011

  • MedStar Franklin Square Medical Center/Weinberg Cancer Institute

    Baltimore, Maryland, 21237

  • Flaget Memorial Hospital

    Bardstown, Kentucky, 40004

  • Indu and Raj Soin Medical Center

    Beavercreek, Ohio, 45431

  • PeaceHealth Saint Joseph Medical Center

    Bellingham, Washington, 98225

  • Saint Charles Health System

    Bend, Oregon, 97701

  • Saint Elizabeth Boardman Hospital

    Boardman, Ohio, 44512

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

  • Central Care Cancer Center - Bolivar

    Bolivar, Missouri, 65613

  • McFarland Clinic PC-Boone

    Boone, Iowa, 50036

  • Cox Cancer Center Branson

    Branson, Missouri, 65616

  • Harrison HealthPartners Hematology and Oncology-Bremerton

    Bremerton, Washington, 98310

  • Harrison Medical Center

    Bremerton, Washington, 98310

  • Saint Joseph Regional Cancer Center

    Bryan, Texas, 77802

  • Providence Saint Joseph Medical Center/Disney Family Cancer Center

    Burbank, California, 91505

  • Highline Medical Center-Main Campus

    Burien, Washington, 98166

  • Loyola Center for Health at Burr Ridge

    Burr Ridge, Illinois, 60527

  • Saint Anthony Regional Hospital

    Carroll, Iowa, 51401

  • Dayton Physicians LLC-Miami Valley South

    Centerville, Ohio, 45459

  • Miami Valley Hospital South

    Centerville, Ohio, 45459

  • Providence Regional Cancer System-Centralia

    Centralia, Washington, 98531

  • Christiana Care Health System-Concord Health Center

    Chadds Ford, Pennsylvania, 19317

  • Marshfield Clinic-Chippewa Center

    Chippewa Falls, Wisconsin, 54729

  • Good Samaritan Hospital - Cincinnati

    Cincinnati, Ohio, 45220

  • Oncology Hematology Care Inc-Kenwood

    Cincinnati, Ohio, 45236

  • Bethesda North Hospital

    Cincinnati, Ohio, 45242

  • TriHealth Cancer Institute-Westside

    Cincinnati, Ohio, 45247

  • TriHealth Cancer Institute-Anderson

    Cincinnati, Ohio, 45255

  • Clackamas Radiation Oncology Center

    Clackamas, Oregon, 97015

  • Providence Cancer Institute Clackamas Clinic

    Clackamas, Oregon, 97015

  • Medical Oncology and Hematology Associates-West Des Moines

    Clive, Iowa, 50325

  • Mercy Cancer Center-West Lakes

    Clive, Iowa, 50325

  • Penrose-Saint Francis Healthcare

    Colorado Springs, Colorado, 80907

  • Rocky Mountain Cancer Centers-Penrose

    Colorado Springs, Colorado, 80907

  • Saint Francis Cancer Center

    Colorado Springs, Colorado, 80923

  • Bay Area Hospital

    Coos Bay, Oregon, 97420

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida, 33146

  • Commonwealth Cancer Center-Corbin

    Corbin, Kentucky, 40701

  • Alegent Health Mercy Hospital

    Council Bluffs, Iowa, 51503

  • Greater Regional Medical Center

    Creston, Iowa, 50801

  • Carle on Vermilion

    Danville, Illinois, 61832

  • Miami Valley Hospital

    Dayton, Ohio, 45409

  • Dayton Physician LLC-Miami Valley Hospital North

    Dayton, Ohio, 45415

  • Miami Valley Hospital North

    Dayton, Ohio, 45415

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

  • Porter Adventist Hospital

    Denver, Colorado, 80210

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • Medical Oncology and Hematology Associates-Des Moines

    Des Moines, Iowa, 50309

  • Broadlawns Medical Center

    Des Moines, Iowa, 50314

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • Mission Cancer and Blood - Laurel

    Des Moines, Iowa, 50314

  • Iowa Lutheran Hospital

    Des Moines, Iowa, 50316

  • Mercy Medical Center

    Durango, Colorado, 81301

  • Southwest Oncology PC

    Durango, Colorado, 81301

  • Marshfield Medical Center-EC Cancer Center

    Eau Claire, Wisconsin, 54701

  • Swedish Cancer Institute-Edmonds

    Edmonds, Washington, 98026

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • Saint Elizabeth Hospital

    Enumclaw, Washington, 98022

  • Providence Regional Cancer Partnership

    Everett, Washington, 98201

  • Saint Francis Hospital

    Federal Way, Washington, 98003

  • Armes Family Cancer Center

    Findlay, Ohio, 45840

  • Blanchard Valley Hospital

    Findlay, Ohio, 45840

  • Orion Cancer Care

    Findlay, Ohio, 45840

  • McFarland Clinic PC-Trinity Cancer Center

    Fort Dodge, Iowa, 50501

  • Trinity Regional Medical Center

    Fort Dodge, Iowa, 50501

  • Mercy Hospital Fort Smith

    Fort Smith, Arkansas, 72903

  • Beebe South Coastal Health Campus

    Frankford, Delaware, 19945

  • Atrium Medical Center-Middletown Regional Hospital

    Franklin, Ohio, 45005-1066

  • Dayton Physicians LLC-Atrium

    Franklin, Ohio, 45005

  • Saint Luke's Cancer Institute - Fruitland

    Fruitland, Idaho, 83619

  • Central Care Cancer Center - Garden City

    Garden City, Kansas, 67846

  • CHI Health Saint Francis

    Grand Island, Nebraska, 68803

  • Central Care Cancer Center - Great Bend

    Great Bend, Kansas, 67530

  • Dayton Physicians LLC-Wayne

    Greenville, Ohio, 45331

  • Wayne Hospital

    Greenville, Ohio, 45331

  • Loyola Medicine Homer Glen

    Homer Glen, Illinois, 60491

  • CHI Saint Vincent Cancer Center Hot Springs

    Hot Springs, Arkansas, 71913

  • Swedish Cancer Institute-Issaquah

    Issaquah, Washington, 98029

  • McFarland Clinic PC-Jefferson

    Jefferson, Iowa, 50129

  • Freeman Health System

    Joplin, Missouri, 64804

  • Mercy Hospital Joplin

    Joplin, Missouri, 64804

  • CHI Health Good Samaritan

    Kearney, Nebraska, 68847

  • Kadlec Clinic Hematology and Oncology

    Kennewick, Washington, 99336

  • Greater Dayton Cancer Center

    Kettering, Ohio, 45409

  • Kettering Medical Center

    Kettering, Ohio, 45429

  • Providence Regional Cancer System-Lacey

    Lacey, Washington, 98503

  • Marshfield Clinic - Ladysmith Center

    Ladysmith, Wisconsin, 54848

  • Saint Anthony Hospital

    Lakewood, Colorado, 80228

  • Saint Clare Hospital

    Lakewood, Washington, 98499

  • Beebe Medical Center

    Lewes, Delaware, 19958

  • Saint Joseph Radiation Oncology Resource Center

    Lexington, Kentucky, 40504

  • Saint Joseph Hospital East

    Lexington, Kentucky, 40509

  • Saint Elizabeth Regional Medical Center

    Lincoln, Nebraska, 68510

  • Littleton Adventist Hospital

    Littleton, Colorado, 80122

  • Saint Joseph London

    London, Kentucky, 40741

  • Longmont United Hospital

    Longmont, Colorado, 80501

  • Rocky Mountain Cancer Centers-Longmont

    Longmont, Colorado, 80501

  • PeaceHealth Saint John Medical Center

    Longview, Washington, 98632

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

  • Jewish Hospital

    Louisville, Kentucky, 40202

  • Saints Mary and Elizabeth Hospital

    Louisville, Kentucky, 40215

  • UofL Health Medical Center Northeast

    Louisville, Kentucky, 40245

  • McFarland Clinic PC-Marshalltown

    Marshalltown, Iowa, 50158

  • Marshfield Medical Center-Marshfield

    Marshfield, Wisconsin, 54449

  • Carle Physician Group-Mattoon/Charleston

    Mattoon, Illinois, 61938

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • Marjorie Weinberg Cancer Center at Loyola-Gottlieb

    Melrose Park, Illinois, 60160

  • Saint Luke's Cancer Institute - Meridian

    Meridian, Idaho, 83642

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • UM Sylvester Comprehensive Cancer Center at Kendall

    Miami, Florida, 33176

  • Marshfield Clinic-Minocqua Center

    Minocqua, Wisconsin, 54548

  • Saint Patrick Hospital - Community Hospital

    Missoula, Montana, 59802

  • Good Samaritan Regional Health Center

    Mount Vernon, Illinois, 62864

  • Saint Luke's Cancer Institute - Nampa

    Nampa, Idaho, 83686

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

  • Delaware Clinical and Laboratory Physicians PA

    Newark, Delaware, 19713

  • Helen F Graham Cancer Center

    Newark, Delaware, 19713

  • Medical Oncology Hematology Consultants PA

    Newark, Delaware, 19713

  • Christiana Care Health System-Christiana Hospital

    Newark, Delaware, 19718

  • Providence Newberg Medical Center

    Newberg, Oregon, 97132

  • Mercy Hospital Oklahoma City

    Oklahoma City, Oklahoma, 73120

  • Alegent Health Immanuel Medical Center

    Omaha, Nebraska, 68122

  • Alegent Health Bergan Mercy Medical Center

    Omaha, Nebraska, 68124

  • Alegent Health Lakeside Hospital

    Omaha, Nebraska, 68130

  • Creighton University Medical Center

    Omaha, Nebraska, 68131

  • Midlands Community Hospital

    Papillion, Nebraska, 68046

  • Parker Adventist Hospital

    Parker, Colorado, 80138

  • University of Pennsylvania/Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

  • Cancer Center at Saint Joseph's

    Phoenix, Arizona, 85004

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona, 85054

  • University of Pittsburgh Cancer Institute (UPCI)

    Pittsburgh, Pennsylvania, 15232

  • UM Sylvester Comprehensive Cancer Center at Plantation

    Plantation, Florida, 33324

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Providence Saint Vincent Medical Center

    Portland, Oregon, 97225

  • Harrison HealthPartners Hematology and Oncology-Poulsbo

    Poulsbo, Washington, 98370

  • Saint Mary Corwin Medical Center

    Pueblo, Colorado, 81004

  • Saint Charles Health System-Redmond

    Redmond, Oregon, 97756

  • Beebe Health Campus

    Rehoboth Beach, Delaware, 19971

  • Marshfield Medical Center-Rice Lake

    Rice Lake, Wisconsin, 54868

  • Reid Health

    Richmond, Indiana, 47374

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Delbert Day Cancer Institute at PCRMC

    Rolla, Missouri, 65401

  • Mercy Clinic-Rolla-Cancer and Hematology

    Rolla, Missouri, 65401

  • Heartland Regional Medical Center

    Saint Joseph, Missouri, 64506

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • Pacific Central Coast Health Center-San Luis Obispo

    San Luis Obispo, California, 93401

  • Mission Hope Medical Oncology - Santa Maria

    Santa Maria, California, 93444

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • TidalHealth Nanticoke / Allen Cancer Center

    Seaford, Delaware, 19973

  • Pacific Gynecology Specialists

    Seattle, Washington, 98104

  • Swedish Medical Center-Ballard Campus

    Seattle, Washington, 98107

  • Swedish Medical Center-Cherry Hill

    Seattle, Washington, 98122-5711

  • Swedish Medical Center-First Hill

    Seattle, Washington, 98122

  • PeaceHealth United General Medical Center

    Sedro-Woolley, Washington, 98284

  • Providence Regional Cancer System-Shelton

    Shelton, Washington, 98584

  • Jewish Hospital Medical Center South

    Shepherdsville, Kentucky, 40165

  • Mercy Hospital Springfield

    Springfield, Missouri, 65804

  • CoxHealth South Hospital

    Springfield, Missouri, 65807

  • Springfield Regional Cancer Center

    Springfield, Ohio, 45504

  • Springfield Regional Medical Center

    Springfield, Ohio, 45505

  • Saint Louis Cancer and Breast Institute-South City

    St Louis, Missouri, 63109

  • Mercy Hospital South

    St Louis, Missouri, 63128

  • Mercy Hospital Saint Louis

    St Louis, Missouri, 63141

  • Marshfield Medical Center-River Region at Stevens Point

    Stevens Point, Wisconsin, 54482

  • Franciscan Research Center-Northwest Medical Plaza

    Tacoma, Washington, 98405

  • Dayton Physicians LLC-Upper Valley

    Troy, Ohio, 45373

  • Upper Valley Medical Center

    Troy, Ohio, 45373

  • Saint Luke's Cancer Institute - Twin Falls

    Twin Falls, Idaho, 83301

  • Carle Cancer Center

    Urbana, Illinois, 61801

  • The Carle Foundation Hospital

    Urbana, Illinois, 61801

  • PeaceHealth Southwest Medical Center

    Vancouver, Washington, 98664

  • Providence Saint Mary Regional Cancer Center

    Walla Walla, Washington, 99362

  • Saint Joseph Warren Hospital

    Warren, Ohio, 44484

  • Mercy Hospital Washington

    Washington, Missouri, 63090

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

  • Marshfield Clinic-Wausau Center

    Wausau, Wisconsin, 54401

  • Methodist West Hospital

    West Des Moines, Iowa, 50266-7700

  • Mercy Medical Center-West Lakes

    West Des Moines, Iowa, 50266

  • Marshfield Medical Center - Weston

    Weston, Wisconsin, 54476

  • Christiana Care Health System-Wilmington Hospital

    Wilmington, Delaware, 19801

  • Marshfield Clinic - Wisconsin Rapids Center

    Wisconsin Rapids, Wisconsin, 54494

  • Providence Regional Cancer System-Yelm

    Yelm, Washington, 98597

  • Rush-Copley Healthcare Center

    Yorkville, Illinois, 60560

  • Saint Elizabeth Youngstown Hospital

    Youngstown, Ohio, 44501

Other trials in United States

About this study

Official title: The BAMM2 (BRAF, Autophagy, MEK Inhibition in Melanoma) Study: A Randomized Double Blind Phase II Study of Dabrafenib and Trametinib With or Without Hydroxychloroquine in Advanced BRAF V600E/K Melanoma With Elevated LDH

This phase II trial investigates how well adding hydroxychloroquine to the standard treatment of dabrafenib and trametinib works to overcome resistance and delay disease progression in treating patients with stage IIIC or IV BRAF V600E/K melanoma. Hydroxychloroquine may cause cell death in tumor cells that rely on a process called "autophagy" for survival. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving hydroxychloroquine together with dabrafenib and trametinib may work better than dabrafenib and trametinib alone to shrink and stabilize the cancer.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the rate of one year progression-free survival (PFS) when hydroxychloroquine sulfate (hydroxychloroquine) or placebo is added to dabrafenib mesylate (dabrafenib) and trametinib dimethyl sulfoxide (trametinib) in advanced BRAFV600E/K melanoma with elevated lactate dehydrogenase (LDH).

SECONDARY OBJECTIVES:

  1. To compare the PFS of both arms. II. To evaluate the best overall response rate by treatment arm. III. To evaluate the complete response (CR) rate by treatment arm. IV. To evaluate the adverse event rate by treatment arm. V. To evaluate overall survival (OS) by treatment arm.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive dabrafenib mesylate orally (PO) twice daily (BID), trametinib dimethyl sulfoxide PO once daily (QD), and hydroxychloroquine sulfate PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and placebo PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 1 year.

Being tested
Dabrafenib mesylate, Hydroxychloroquine, Placebo Administration, Trametinib dimethyl sulfoxide

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dabrafenib mesylateDrug

    Also called NSC 763760, GSK2118436A (free base), Tafinlar®, GSK2118436B

    Given PO

  • HydroxychloroquineDrug

    Also called Hydroxychloroquine sulfate, Plaquenil

    Given PO

  • Placebo AdministrationDrug

    Given PO

  • Trametinib dimethyl sulfoxideDrug

    Also called trametinib, GSK1120212B, TMT212-NXA, JTP-74057

    Given PO

Study groups in NCT04527549
Study groupRoleWhat they receive
Arm A (dabrafenib, trametinib, hydroxychloroquine)ExperimentalPatients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and hydroxychloroquine sulfate PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Dabrafenib mesylate; Drug: Hydroxychloroquine; Drug: Trametinib dimethyl sulfoxide
Arm B (dabrafenib, trametinib, placebo)Active comparatorPatients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and placebo PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Dabrafenib mesylate; Drug: Placebo Administration; Drug: Trametinib dimethyl sulfoxide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. One-year Progression-free Survival Rate

    Progression-free survival is defined as the time from randomization to progression or death, whichever occurs first. Progression is defined as appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions, or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

    One-year progression-free survival rate is estimated from the Kaplan-Meier progression-free survival curve.

    Measured: Assessed every 2 months until 6 months after completion of study treatment, up to 1 year

Secondary outcomes (5)

  1. Progression-free Survival

    Progression-free survival is defined as the time from randomization to progression or death, whichever occurs first. Progression is defined as appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions, or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

    Measured: Assessed every 2 months until 6 months after completion of study treatment, up to 3 years

  2. Proportion of Patients With Best Overall Response

    Best overall response is defined as either complete response or partial response.

    Complete response is defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.

    Partial response is defined as persistence of one or more non-target lesion(s) and at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: Assessed every 2 months until 6 months after completion of study treatment, up to 3 years

  3. Proportion of Patients With Complete Response

    Complete response is defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.

    Measured: Assessed every 2 months until 6 months after completion of study treatment, up to 3 years

  4. Adverse Event Rate

    Proportion of patients with treatment-related adverse events of grade 3 or higher.

    Measured: Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 3 years

  5. Overall Survival

    Overall survival is defined as the time from randomization to death or date last known alive.

    Measured: Assessed every 2 months until 6 months after completion of study treatment, up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Aug 2020
  2. Study start1 Jun 2021
  3. Primary completion8 Jan 2024
  4. Study completion8 Jan 2024

Why it stopped: Slow accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04527549
Sponsor's protocol ID
EA6191
Other IDs
NCI-2020-04552, EA6191, EA6191, U10CA180820
Status last verified
Sep 2026
First submitted
24 Aug 2020
Last updated
6 Oct 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.

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