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在 IIIC 或 IV 期 BRAF V600E/K 黑色素瘤中测试 Dabrafenib 和 Trametinib 加或不加羟氯喹

2026年9月11日 更新者：ECOG-ACRIN Cancer Research Group

BAMM2（黑色素瘤中的 BRAF、自噬、MEK 抑制）研究：Dabrafenib 和 Trametinib 联合或不联合羟氯喹治疗晚期 BRAF V600E/K 黑色素瘤的随机双盲 II 期研究

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.

研究概览

地位

终止

条件

干预/治疗

详细说明

PRIMARY OBJECTIVE:

I. 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:

I. 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.

研究类型

介入性

注册 (实际的)

5

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 美国
    • Alaska
      • Anchorage、Alaska、美国、98508
        • Anchorage Associates in Radiation Medicine
      • Anchorage、Alaska、美国、99508
        • Alaska Breast Care and Surgery LLC
      • Anchorage、Alaska、美国、99508
        • Alaska Oncology and Hematology LLC
      • Anchorage、Alaska、美国、99508
        • Alaska Women's Cancer Care
      • Anchorage、Alaska、美国、99508
        • Anchorage Oncology Centre
      • Anchorage、Alaska、美国、99508
        • Katmai Oncology Group
      • Anchorage、Alaska、美国、99508
        • Providence Alaska Medical Center
      • Anchorage、Alaska、美国、99504
        • Anchorage Radiation Therapy Center
    • Arizona
      • Phoenix、Arizona、美国、85054
        • Mayo Clinic Hospital in Arizona
      • Phoenix、Arizona、美国、85004
        • Cancer Center at Saint Joseph's
      • Scottsdale、Arizona、美国、85259
        • Mayo Clinic in Arizona
    • Arkansas
      • Fort Smith、Arkansas、美国、72903
        • Mercy Hospital Fort Smith
      • Hot Springs、Arkansas、美国、71913
        • CHI Saint Vincent Cancer Center Hot Springs
    • California
      • Arroyo Grande、California、美国、93420
        • Mission Hope Medical Oncology - Arroyo Grande
      • Burbank、California、美国、91505
        • Providence Saint Joseph Medical Center/Disney Family Cancer Center
      • Los Angeles、California、美国、90048
        • Cedars Sinai Medical Center
      • San Luis Obispo、California、美国、93401
        • Pacific Central Coast Health Center-San Luis Obispo
      • Santa Maria、California、美国、93444
        • Mission Hope Medical Oncology - Santa Maria
    • Colorado
      • Colorado Springs、Colorado、美国、80907
        • Penrose-Saint Francis Healthcare
      • Colorado Springs、Colorado、美国、80907
        • Rocky Mountain Cancer Centers-Penrose
      • Colorado Springs、Colorado、美国、80923
        • Saint Francis Cancer Center
      • Denver、Colorado、美国、80210
        • Porter Adventist Hospital
      • Durango、Colorado、美国、81301
        • Mercy Medical Center
      • Durango、Colorado、美国、81301
        • Southwest Oncology PC
      • Lakewood、Colorado、美国、80228
        • Saint Anthony Hospital
      • Littleton、Colorado、美国、80122
        • Littleton Adventist Hospital
      • Longmont、Colorado、美国、80501
        • Longmont United Hospital
      • Longmont、Colorado、美国、80501
        • Rocky Mountain Cancer Centers-Longmont
      • Parker、Colorado、美国、80138
        • Parker Adventist Hospital
      • Pueblo、Colorado、美国、81004
        • Saint Mary Corwin Medical Center
    • Delaware
      • Frankford、Delaware、美国、19945
        • Beebe South Coastal Health Campus
      • Lewes、Delaware、美国、19958
        • Beebe Medical Center
      • Newark、Delaware、美国、19713
        • Helen F Graham Cancer Center
      • Newark、Delaware、美国、19713
        • Delaware Clinical and Laboratory Physicians PA
      • Newark、Delaware、美国、19713
        • Medical Oncology Hematology Consultants PA
      • Newark、Delaware、美国、19718
        • Christiana Care Health System-Christiana Hospital
      • Rehoboth Beach、Delaware、美国、19971
        • Beebe Health Campus
      • Seaford、Delaware、美国、19973
        • TidalHealth Nanticoke / Allen Cancer Center
      • Wilmington、Delaware、美国、19801
        • Christiana Care Health System-Wilmington Hospital
    • District of Columbia
      • Washington D.C.、District of Columbia、美国、20007
        • MedStar Georgetown University Hospital
    • Florida
      • Aventura、Florida、美国、33180
        • UM Sylvester Comprehensive Cancer Center at Aventura
      • Coral Gables、Florida、美国、33146
        • UM Sylvester Comprehensive Cancer Center at Coral Gables
      • Deerfield Beach、Florida、美国、33442
        • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
      • Miami、Florida、美国、33136
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
      • Miami、Florida、美国、33176
        • UM Sylvester Comprehensive Cancer Center at Kendall
      • Plantation、Florida、美国、33324
        • UM Sylvester Comprehensive Cancer Center at Plantation
    • Idaho
      • Boise、Idaho、美国、83712
        • Saint Luke's Cancer Institute - Boise
      • Fruitland、Idaho、美国、83619
        • Saint Luke's Cancer Institute - Fruitland
      • Meridian、Idaho、美国、83642
        • Saint Luke's Cancer Institute - Meridian
      • Nampa、Idaho、美国、83686
        • Saint Luke's Cancer Institute - Nampa
      • Twin Falls、Idaho、美国、83301
        • Saint Luke's Cancer Institute - Twin Falls
    • Illinois
      • Alton、Illinois、美国、62002
        • Saint Anthony's Health
      • Aurora、Illinois、美国、60504
        • Rush - Copley Medical Center
      • Burr Ridge、Illinois、美国、60527
        • Loyola Center for Health at Burr Ridge
      • Danville、Illinois、美国、61832
        • Carle on Vermilion
      • Effingham、Illinois、美国、62401
        • Carle Physician Group-Effingham
      • Homer Glen、Illinois、美国、60491
        • Loyola Medicine Homer Glen
      • Mattoon、Illinois、美国、61938
        • Carle Physician Group-Mattoon/Charleston
      • Maywood、Illinois、美国、60153
        • Loyola University Medical Center
      • Melrose Park、Illinois、美国、60160
        • Marjorie Weinberg Cancer Center at Loyola-Gottlieb
      • Mount Vernon、Illinois、美国、62864
        • Good Samaritan Regional Health Center
      • Urbana、Illinois、美国、61801
        • Carle Cancer Center
      • Urbana、Illinois、美国、61801
        • The Carle Foundation Hospital
      • Yorkville、Illinois、美国、60560
        • Rush-Copley Healthcare Center
    • Indiana
      • Richmond、Indiana、美国、47374
        • Reid Health
    • Iowa
      • Ames、Iowa、美国、50010
        • McFarland Clinic PC - Ames
      • Ames、Iowa、美国、50010
        • Mary Greeley Medical Center
      • Boone、Iowa、美国、50036
        • McFarland Clinic PC-Boone
      • Carroll、Iowa、美国、51401
        • Saint Anthony Regional Hospital
      • Clive、Iowa、美国、50325
        • Mercy Cancer Center-West Lakes
      • Clive、Iowa、美国、50325
        • Medical Oncology and Hematology Associates-West Des Moines
      • Council Bluffs、Iowa、美国、51503
        • Alegent Health Mercy Hospital
      • Creston、Iowa、美国、50801
        • Greater Regional Medical Center
      • Des Moines、Iowa、美国、50309
        • Iowa Methodist Medical Center
      • Des Moines、Iowa、美国、50314
        • Mercy Medical Center - Des Moines
      • Des Moines、Iowa、美国、50309
        • Medical Oncology and Hematology Associates-Des Moines
      • Des Moines、Iowa、美国、50314
        • Broadlawns Medical Center
      • Des Moines、Iowa、美国、50314
        • Mission Cancer and Blood - Laurel
      • Des Moines、Iowa、美国、50316
        • Iowa Lutheran Hospital
      • Fort Dodge、Iowa、美国、50501
        • McFarland Clinic PC-Trinity Cancer Center
      • Fort Dodge、Iowa、美国、50501
        • Trinity Regional Medical Center
      • Jefferson、Iowa、美国、50129
        • McFarland Clinic PC-Jefferson
      • Marshalltown、Iowa、美国、50158
        • McFarland Clinic PC-Marshalltown
      • West Des Moines、Iowa、美国、50266-7700
        • Methodist West Hospital
      • West Des Moines、Iowa、美国、50266
        • Mercy Medical Center-West Lakes
    • Kansas
      • Garden City、Kansas、美国、67846
        • Central Care Cancer Center - Garden City
      • Great Bend、Kansas、美国、67530
        • Central Care Cancer Center - Great Bend
    • Kentucky
      • Bardstown、Kentucky、美国、40004
        • Flaget Memorial Hospital
      • Corbin、Kentucky、美国、40701
        • Commonwealth Cancer Center-Corbin
      • Lexington、Kentucky、美国、40504
        • Saint Joseph Radiation Oncology Resource Center
      • Lexington、Kentucky、美国、40509
        • Saint Joseph Hospital East
      • London、Kentucky、美国、40741
        • Saint Joseph London
      • Louisville、Kentucky、美国、40202
        • Jewish Hospital
      • Louisville、Kentucky、美国、40245
        • UofL Health Medical Center Northeast
      • Louisville、Kentucky、美国、40215
        • Saints Mary and Elizabeth Hospital
      • Shepherdsville、Kentucky、美国、40165
        • Jewish Hospital Medical Center South
    • Maryland
      • Baltimore、Maryland、美国、21237
        • MedStar Franklin Square Medical Center/Weinberg Cancer Institute
    • Minnesota
      • Rochester、Minnesota、美国、55905
        • Mayo Clinic in Rochester
    • Missouri
      • Ballwin、Missouri、美国、63011
        • Saint Louis Cancer and Breast Institute-Ballwin
      • Bolivar、Missouri、美国、65613
        • Central Care Cancer Center - Bolivar
      • Branson、Missouri、美国、65616
        • Cox Cancer Center Branson
      • Joplin、Missouri、美国、64804
        • Freeman Health System
      • Joplin、Missouri、美国、64804
        • Mercy Hospital Joplin
      • Rolla、Missouri、美国、65401
        • Delbert Day Cancer Institute at PCRMC
      • Rolla、Missouri、美国、65401
        • Mercy Clinic-Rolla-Cancer and Hematology
      • Saint Joseph、Missouri、美国、64506
        • Heartland Regional Medical Center
      • Springfield、Missouri、美国、65807
        • CoxHealth South Hospital
      • Springfield、Missouri、美国、65804
        • Mercy Hospital Springfield
      • St Louis、Missouri、美国、63141
        • Mercy Hospital Saint Louis
      • St Louis、Missouri、美国、63128
        • Mercy Hospital South
      • St Louis、Missouri、美国、63109
        • Saint Louis Cancer and Breast Institute-South City
      • Washington、Missouri、美国、63090
        • Mercy Hospital Washington
    • Montana
      • Missoula、Montana、美国、59802
        • Saint Patrick Hospital - Community Hospital
    • Nebraska
      • Grand Island、Nebraska、美国、68803
        • CHI Health Saint Francis
      • Kearney、Nebraska、美国、68847
        • CHI Health Good Samaritan
      • Lincoln、Nebraska、美国、68510
        • Saint Elizabeth Regional Medical Center
      • Omaha、Nebraska、美国、68124
        • Alegent Health Bergan Mercy Medical Center
      • Omaha、Nebraska、美国、68122
        • Alegent Health Immanuel Medical Center
      • Omaha、Nebraska、美国、68130
        • Alegent Health Lakeside Hospital
      • Omaha、Nebraska、美国、68131
        • Creighton University Medical Center
      • Papillion、Nebraska、美国、68046
        • Midlands Community Hospital
    • New York
      • New York、New York、美国、10016
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
    • Ohio
      • Beavercreek、Ohio、美国、45431
        • Indu and Raj Soin Medical Center
      • Boardman、Ohio、美国、44512
        • Saint Elizabeth Boardman Hospital
      • Centerville、Ohio、美国、45459
        • Miami Valley Hospital South
      • Centerville、Ohio、美国、45459
        • Dayton Physicians LLC-Miami Valley South
      • Cincinnati、Ohio、美国、45220
        • Good Samaritan Hospital - Cincinnati
      • Cincinnati、Ohio、美国、45242
        • Bethesda North Hospital
      • Cincinnati、Ohio、美国、45236
        • Oncology Hematology Care Inc-Kenwood
      • Cincinnati、Ohio、美国、45247
        • TriHealth Cancer Institute-Westside
      • Cincinnati、Ohio、美国、45255
        • TriHealth Cancer Institute-Anderson
      • Dayton、Ohio、美国、45409
        • Miami Valley Hospital
      • Dayton、Ohio、美国、45415
        • Dayton Physician LLC-Miami Valley Hospital North
      • Dayton、Ohio、美国、45415
        • Miami Valley Hospital North
      • Findlay、Ohio、美国、45840
        • Blanchard Valley Hospital
      • Findlay、Ohio、美国、45840
        • Armes Family Cancer Center
      • Findlay、Ohio、美国、45840
        • Orion Cancer Care
      • Franklin、Ohio、美国、45005-1066
        • Atrium Medical Center-Middletown Regional Hospital
      • Franklin、Ohio、美国、45005
        • Dayton Physicians LLC-Atrium
      • Greenville、Ohio、美国、45331
        • Wayne Hospital
      • Greenville、Ohio、美国、45331
        • Dayton Physicians LLC-Wayne
      • Kettering、Ohio、美国、45429
        • Kettering Medical Center
      • Kettering、Ohio、美国、45409
        • Greater Dayton Cancer Center
      • Springfield、Ohio、美国、45505
        • Springfield Regional Medical Center
      • Springfield、Ohio、美国、45504
        • Springfield Regional Cancer Center
      • Troy、Ohio、美国、45373
        • Upper Valley Medical Center
      • Troy、Ohio、美国、45373
        • Dayton Physicians LLC-Upper Valley
      • Warren、Ohio、美国、44484
        • Saint Joseph Warren Hospital
      • Youngstown、Ohio、美国、44501
        • Saint Elizabeth Youngstown Hospital
    • Oklahoma
      • Oklahoma City、Oklahoma、美国、73120
        • Mercy Hospital Oklahoma City
    • Oregon
      • Bend、Oregon、美国、97701
        • Saint Charles Health System
      • Clackamas、Oregon、美国、97015
        • Clackamas Radiation Oncology Center
      • Clackamas、Oregon、美国、97015
        • Providence Cancer Institute Clackamas Clinic
      • Coos Bay、Oregon、美国、97420
        • Bay Area Hospital
      • Newberg、Oregon、美国、97132
        • Providence Newberg Medical Center
      • Portland、Oregon、美国、97213
        • Providence Portland Medical Center
      • Portland、Oregon、美国、97225
        • Providence Saint Vincent Medical Center
      • Redmond、Oregon、美国、97756
        • Saint Charles Health System-Redmond
    • Pennsylvania
      • Chadds Ford、Pennsylvania、美国、19317
        • Christiana Care Health System-Concord Health Center
      • Philadelphia、Pennsylvania、美国、19104
        • University of Pennsylvania/Abramson Cancer Center
      • Pittsburgh、Pennsylvania、美国、15232
        • University of Pittsburgh Cancer Institute (UPCI)
    • Texas
      • Bryan、Texas、美国、77802
        • Saint Joseph Regional Cancer Center
    • Utah
      • Salt Lake City、Utah、美国、84112
        • Huntsman Cancer Institute/University of Utah
    • Washington
      • Aberdeen、Washington、美国、98520
        • Providence Regional Cancer System-Aberdeen
      • Bellingham、Washington、美国、98225
        • PeaceHealth Saint Joseph Medical Center
      • Bremerton、Washington、美国、98310
        • Harrison HealthPartners Hematology and Oncology-Bremerton
      • Bremerton、Washington、美国、98310
        • Harrison Medical Center
      • Burien、Washington、美国、98166
        • Highline Medical Center-Main Campus
      • Centralia、Washington、美国、98531
        • Providence Regional Cancer System-Centralia
      • Edmonds、Washington、美国、98026
        • Swedish Cancer Institute-Edmonds
      • Enumclaw、Washington、美国、98022
        • Saint Elizabeth Hospital
      • Everett、Washington、美国、98201
        • Providence Regional Cancer Partnership
      • Federal Way、Washington、美国、98003
        • Saint Francis Hospital
      • Issaquah、Washington、美国、98029
        • Swedish Cancer Institute-Issaquah
      • Kennewick、Washington、美国、99336
        • Kadlec Clinic Hematology and Oncology
      • Lacey、Washington、美国、98503
        • Providence Regional Cancer System-Lacey
      • Lakewood、Washington、美国、98499
        • Saint Clare Hospital
      • Longview、Washington、美国、98632
        • PeaceHealth Saint John Medical Center
      • Poulsbo、Washington、美国、98370
        • Harrison HealthPartners Hematology and Oncology-Poulsbo
      • Seattle、Washington、美国、98107
        • Swedish Medical Center-Ballard Campus
      • Seattle、Washington、美国、98122
        • Swedish Medical Center-First Hill
      • Seattle、Washington、美国、98104
        • Pacific Gynecology Specialists
      • Seattle、Washington、美国、98122-5711
        • Swedish Medical Center-Cherry Hill
      • Sedro-Woolley、Washington、美国、98284
        • PeaceHealth United General Medical Center
      • Shelton、Washington、美国、98584
        • Providence Regional Cancer System-Shelton
      • Tacoma、Washington、美国、98405
        • Franciscan Research Center-Northwest Medical Plaza
      • Vancouver、Washington、美国、98664
        • PeaceHealth Southwest Medical Center
      • Walla Walla、Washington、美国、99362
        • Providence Saint Mary Regional Cancer Center
      • Yelm、Washington、美国、98597
        • Providence Regional Cancer System-Yelm
    • Wisconsin
      • Chippewa Falls、Wisconsin、美国、54729
        • Marshfield Clinic-Chippewa Center
      • Eau Claire、Wisconsin、美国、54701
        • Marshfield Medical Center-EC Cancer Center
      • Ladysmith、Wisconsin、美国、54848
        • Marshfield Clinic - Ladysmith Center
      • Marshfield、Wisconsin、美国、54449
        • Marshfield Medical Center-Marshfield
      • Minocqua、Wisconsin、美国、54548
        • Marshfield Clinic-Minocqua Center
      • Rice Lake、Wisconsin、美国、54868
        • Marshfield Medical Center-Rice Lake
      • Stevens Point、Wisconsin、美国、54482
        • Marshfield Medical Center-River Region at Stevens Point
      • Wausau、Wisconsin、美国、54401
        • Marshfield Clinic-Wausau Center
      • Weston、Wisconsin、美国、54476
        • Marshfield Medical Center - Weston
      • Wisconsin Rapids、Wisconsin、美国、54494
        • Marshfield Clinic - Wisconsin Rapids Center

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • 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
    • 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

Exclusion Criteria:

  • 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

  • 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

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：双倍的

武器和干预

参与者组/臂
干预/治疗
实验性的：Arm A (dabrafenib, trametinib, hydroxychloroquine)

Patients 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.
药品：Dabrafenib mesylate

Given PO

其他名称：
  • GSK2118436B
  • Tafinlar®
  • 国家安全委员会 763760
  • GSK2118436A（自由碱）
药品：Hydroxychloroquine

Given PO

其他名称：
  • 普拉奎尼
  • 硫酸羟氯喹
药品：Trametinib dimethyl sulfoxide

Given PO

其他名称：
  • JTP-74057
  • 曲美替尼
  • 曲美力®
  • TMT212-NXA
  • JTP-78296
  • JTP-75303
  • GSK1120212B
  • 国家安全委员会 763093
有源比较器：Arm B (dabrafenib, trametinib, placebo)

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.
药品：Placebo Administration

Given PO

药品：Dabrafenib mesylate

Given PO

其他名称：
  • GSK2118436B
  • Tafinlar®
  • 国家安全委员会 763760
  • GSK2118436A（自由碱）
药品：Trametinib dimethyl sulfoxide

Given PO

其他名称：
  • JTP-74057
  • 曲美替尼
  • 曲美力®
  • TMT212-NXA
  • JTP-78296
  • JTP-75303
  • GSK1120212B
  • 国家安全委员会 763093

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
One-year Progression-free Survival Rate
大体时间：Assessed every 2 months until 6 months after completion of study treatment, up to 1 year

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

次要结果测量

结果测量
措施说明
大体时间
Progression-free Survival
大体时间：Assessed every 2 months until 6 months after completion of study treatment, up to 3 years

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.
Assessed every 2 months until 6 months after completion of study treatment, up to 3 years
Proportion of Patients With Best Overall Response
大体时间：Assessed every 2 months until 6 months after completion of study treatment, up to 3 years

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.
Assessed every 2 months until 6 months after completion of study treatment, up to 3 years
Proportion of Patients With Complete Response
大体时间：Assessed every 2 months until 6 months after completion of study treatment, up to 3 years

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.
Assessed every 2 months until 6 months after completion of study treatment, up to 3 years
Adverse Event Rate
大体时间：Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 3 years

Proportion of patients with treatment-related adverse events of grade 3 or higher.
Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 3 years
Overall Survival
大体时间：Assessed every 2 months until 6 months after completion of study treatment, up to 3 years

Overall survival is defined as the time from randomization to death or date last known alive.
Assessed every 2 months until 6 months after completion of study treatment, up to 3 years

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

ECOG-ACRIN Cancer Research Group

合作者

National Cancer Institute (NCI)

调查人员

  • 首席研究员：Ravi Amaravadi、ECOG-ACRIN Cancer Research Group

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2021年6月1日

初级完成 (实际的)

2024年1月8日

研究完成 (实际的)

2024年1月8日

研究注册日期

首次提交

2020年8月24日

首先提交符合 QC 标准的

2020年8月24日

首次发布 (实际的)

2020年8月26日

研究记录更新

最后更新发布 (实际的)

2026年10月6日

上次提交的符合 QC 标准的更新

2026年9月11日

最后验证

2026年9月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • EA6191
  • U10CA180820 (美国 NIH 拨款/合同)
  • EA6191 (其他标识符：CTEP)
  • NCI-2020-04552 (注册表标识符：CTRP (Clinical Trial Reporting Program))
  • EA6191 (其他标识符：ECOG-ACRIN Cancer Research Group)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

是的

IPD 计划说明

Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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