AzTrials
AzTrials

Stage III Cutaneous Melanoma AJCC v7Phase 2NCT02196181

Testing Two Different Treatment Schedules of Dabrafenib and Trametinib for Skin Cancer Which Has Spread

A Phase 2 study testing Biospecimen Collection, Computed Tomography and Dabrafenib Mesylate in people with Stage III Cutaneous Melanoma AJCC v7 and Stage IV Cutaneous Melanoma AJCC v6 and v7, run by National Cancer Institute (NCI) at 752 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

Search all trials

Trial summary

This phase II trial compares the effect of dabrafenib and trametinib given continuously to given with a break in treatment (intermittent) in treating patients with stage III-IV melanoma that cannot be removed by surgery and contains a B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutation. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Computed Tomography and Dabrafenib Mesylate
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
280 participants
Where
752 sitesUnited States
Study dates
19 Sep 2014to 15 Mar 2027
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

  • STEP 1: REGISTRATION
  • Patients must have histologically or cytologically confirmed stage IV or unresectable stage III BRAF V600E or BRAF V600K mutant melanoma
  • Patients must have BRAF V600E or BRAF V600K mutation identified by a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory; acceptable analytic techniques include but are not restricted to DNA sequencing, pyrosequencing, polymerase chain reaction (PCR), melting point assays, and immunohistochemistry
  • Contrast-enhanced CT scans of the neck, chest, abdomen and pelvis are required; a whole body PET/CT scan with diagnostic quality images and intravenous iodinated contrast may be used in lieu of a contrast enhanced CT of the neck, chest, abdomen and pelvis; contrast may be omitted if the treating investigator believes that exposure to contrast poses an excessive risk to the patient; patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; all measurable lesions must be assessed within 28 days prior to registration; tests to assess non-measurable disease must be performed within 42 days prior to registration; all disease must be assessed and documented on the Baseline Tumor Assessment Form (RECIST 1.1)
  • Patients must not have received a prior BRAF or MEK inhibitor
  • Patients with a history of brain metastases are eligible if the patient is asymptomatic with no residual neurological dysfunction and has not received enzyme-reducing anti-epileptic drugs or corticosteroids for at least 7 days prior to registration
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  • Patients must not have received any anti-cancer drug within 28 days prior to registration, and must not have received any nitrosoureas or mitomycin C within 42 days prior to registration
  • Patients must not have received any major surgery or immunotherapy within 28 days prior to registration
  • Patients must not have any unresolved toxicity greater than National Cancer Institute (NCI)-CTCAE version (v) 4.0 grade 1 from previous anti-cancer therapy except alopecia within 7 days prior to registration
  • Patients must be age >= 18 years of age
  • Absolute neutrophil count (ANC) >= 1,200/ul (obtained within 28 days prior to registration)
  • Platelets >= 100,000/ul (obtained within 28 days prior to registration)
  • Hemoglobin >= 9 g/dL (obtained within 28 days prior to registration)
  • Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (or =< 2.5 x upper limit of normal [ULN] with Gilbert's syndrome) (obtained within 28 days prior to registration)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x IULN (or < 5 x IULN for patients with known liver metastases) (obtained within 28 days prior to registration)
  • Serum albumin >= 2.5 g/dL (obtained within 28 days prior to registration)
  • Serum creatinine =< 1.5 mg/dL OR measured or calculated creatinine clearance >= 50 mL/min; creatinine measurements must be obtained within 28 days prior to registration
  • Patients must have lactate dehydrogenase (LDH) obtained within 28 days prior to registration in order to obtain baseline stratification information
  • Patients must have a left ventricular ejection fraction (LVEF) >= institutional lower limit of normal (ILLN) by ECHO or MUGA within 28 days prior to registration
  • Patients must have corrected QT (QTc) =< 480 msec by electrocardiogram (ECG) (corrected using the Bazett's formula) within 28 days prior to registration
  • Patients with known history or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR) are not eligible:
  • History of RVO or CSR, or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)
  • Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as:
  • Evidence of new optic disc cupping
  • Evidence of new visual field defects
  • Intraocular pressure > 21 mmHg
  • NOTE: ophthalmic exam is required for all patients; exam must be obtained within 28 days prior to registration
  • Patients must be able to take oral medications; patients must not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of protocol treatment (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
  • Patients receiving anticoagulation treatment are allowed to participate with international normalized ratio (INR) established within the therapeutic range
  • Patients must not have a history of pneumonitis or interstitial lung disease
  • Patients must not have any grade II/III/IV cardiac disease as defined by the New York Heart Association criteria (i.e., patients with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort), unstable angina pectoris, myocardial infarction within 6 months, or serious uncontrolled cardiac arrhythmia; abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis]) can be entered on study; patients with a history of atrial fibrillation must have atrial fibrillation controlled for at least 30 days prior to registration
  • Patients with known hepatitis B or hepatitis C are not eligible, regardless of concomitant antiretroviral therapy or current viral load
  • Patients with known human immunodeficiency virus (HIV) may be eligible providing they meet the following additional criteria:
  • Cluster of differentiation (CD)4 cells >= 500/uL
  • Serum HIV viral load of < 25,000 IU/ml
  • No current antiretroviral therapy
  • Tests must be obtained within 28 days prior to registration; patients who are HIV positive (+) and do not meet all of these criteria are not eligible for this study (HIV/hepatitis testing are not required for patients without known infection)
  • Pre-study history and physical must be obtained with 28 days prior to registration
  • Patients must have dermatology exam obtained within 28 days prior to registration to obtain baseline measurement; exam to be performed by treating physician or designated dermatologist
  • Patients must have Zubrod performance status of 0, 1 or 2
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years; exception: patients with known history of colon cancer, cancer of the pancreas, or any cancer known to harbor an activating RAS mutation are ineligible regardless of stage or time since diagnosis
  • Patients must not be pregnant or nursing because of the risk of fetal harm; women/men of reproductive potential must have agreed to use an effective contraceptive method; 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 patient 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; hormonal contraception is not allowed due to drug interactions which can render hormonal contraceptives ineffective
  • Patients must be offered the opportunity to participate in specimen banking
  • Patients with cutaneous or superficial lesions that do not require imaging guidance for biopsy must be willing to undergo biopsies for tissue submission and blood draws for translational medicine
  • Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
  • As a part of the Oncology Patient Enrollment Network (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
  • STEP 2: RANDOMIZATION
  • After completing one cycle of therapy, patients will be registered for randomization between intermittent and continuous dosing, provided that they were eligible for the initial step 1 registration and satisfy the following criteria
  • Patients must not have unequivocal disease progression (by RECIST v1.1) during the first cycle; patients must have disease assessed using the same method as baseline within +/- 5 days of the day 56 scheduled assessment (between days 51-55 of cycle 1, or days 1-5 of cycle 2); all disease must be assessed and documented on the follow-up tumor assessment form (RECIST 1.1)
  • Patients must be registered to step 2: randomization within +/- 5 days of starting cycle 2; patients MUST NOT be registered prior to the day 56 disease assessment

Who cannot join

None listed.

Trial locations and contacts

752 sites in 1 country.

300 sites in 1 country

United States300 sites

  • Hawaii Cancer Care - Westridge

    ‘Aiea, Hawaii, 96701

  • Pali Momi Medical Center

    ‘Aiea, Hawaii, 96701

  • Queen's Cancer Center - Pearlridge

    ‘Aiea, Hawaii, 96701

  • The Cancer Center of Hawaii-Pali Momi

    ‘Aiea, Hawaii, 96701

  • Providence Regional Cancer System-Aberdeen

    Aberdeen, Washington, 98520

  • Jefferson Abington Hospital

    Abington, Pennsylvania, 19001

  • Hickman Cancer Center

    Adrian, Michigan, 49221

  • AdventHealth Altamonte

    Altamonte Springs, Florida, 32701

  • American Fork Hospital / Huntsman Intermountain Cancer Center

    American Fork, Utah, 84003

  • Mary Greeley Medical Center

    Ames, Iowa, 50010

  • McFarland Clinic - Ames

    Ames, Iowa, 50010

  • Community Hospital of Anaconda

    Anaconda, Montana, 59711

  • Cancer Care Center at Island Hospital

    Anacortes, Washington, 98221

  • Kaiser Permanente-Anaheim

    Anaheim, California, 92806

  • 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 Regional Hospital

    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

  • AnMed Health Cancer Center

    Anderson, South Carolina, 29621

  • University of Michigan Rogel Cancer Center

    Ann Arbor, Michigan, 48109

  • Kaiser Permanente-Deer Valley Medical Center

    Antioch, California, 94531

  • PCR Oncology

    Arroyo Grande, California, 93420

  • Mission Hospital

    Asheville, North Carolina, 28801

  • AdventHealth Infusion Center Asheville

    Asheville, North Carolina, 28803

  • Messino Cancer Centers

    Asheville, North Carolina, 28806

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • MultiCare Auburn Medical Center

    Auburn, Washington, 98001

  • Harold Alfond Center for Cancer Care

    Augusta, Maine, 04330

  • Rocky Mountain Cancer Centers-Aurora

    Aurora, Colorado, 80012

  • The Medical Center of Aurora

    Aurora, Colorado, 80012

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • Rush-Copley Medical Center

    Aurora, Illinois, 60504

  • Mount Sinai Comprehensive Cancer Center at Aventura

    Aventura, Florida, 33180

  • Virginia Mason Bainbridge Island Medical Center

    Bainbridge Island, Washington, 98110

  • Saint Alphonsus Cancer Care Center-Baker City

    Baker City, Oregon, 97814

  • Kaiser Permanente-Baldwin Park

    Baldwin Park, California, 91706

  • Greater Baltimore Medical Center

    Baltimore, Maryland, 21204

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • CommonSpirit Saint Joseph Hospital - Bardstown

    Bardstown, Kentucky, 40004

  • Bronson Battle Creek

    Battle Creek, Michigan, 49017

  • UPMC-Heritage Valley Health System Beaver

    Beaver, Pennsylvania, 15009

  • Indu and Raj Soin Medical Center

    Beavercreek, Ohio, 45431

  • MaineHealth Waldo Hospital

    Belfast, Maine, 04915

  • Overlake Medical Center

    Bellevue, Washington, 98004

  • Swedish Cancer Institute-Eastside Oncology Hematology

    Bellevue, Washington, 98005

  • Kaiser Permanente-Bellflower

    Bellflower, California, 90706

  • PeaceHealth Saint Joseph Medical Center

    Bellingham, Washington, 98225

  • Strecker Cancer Center-Belpre

    Belpre, Ohio, 45714

  • Saint Charles Health System

    Bend, Oregon, 97701

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889-5600

  • University of Iowa Healthcare Cancer Services Quad Cities

    Bettendorf, Iowa, 52722

  • MaineHealth Maine Medical Center - Biddeford

    Biddeford, Maine, 04005

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • Saint Vincent Healthcare

    Billings, Montana, 59101

  • Saint Vincent Frontier Cancer Center

    Billings, Montana, 59102

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • OSF Saint Joseph Medical Center

    Bloomington, Illinois, 61701

  • Illinois CancerCare-Bloomington

    Bloomington, Illinois, 61704

  • Saint Elizabeth Boardman Hospital

    Boardman, Ohio, 44512

  • Saint Alphonsus Cancer Care Center-Boise

    Boise, Idaho, 83706

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

  • Central Care Cancer Center - Bolivar

    Bolivar, Missouri, 65613

  • Parkland Health Center-Bonne Terre

    Bonne Terre, Missouri, 63628

  • McFarland Clinic - Boone

    Boone, Iowa, 50036

  • Boston Medical Center

    Boston, Massachusetts, 02118

  • Boulder Community Foothills Hospital

    Boulder, Colorado, 80303

  • Rocky Mountain Cancer Centers-Boulder

    Boulder, Colorado, 80304

  • Bozeman Health Deaconess Hospital

    Bozeman, Montana, 59715

  • Essentia Health Saint Joseph's Medical Center

    Brainerd, Minnesota, 56401

  • Cox Cancer Center Branson

    Branson, Missouri, 65616

  • Lafayette Family Cancer Center-EMMC

    Brewer, Maine, 04412

  • Ocean University Medical Center

    Brick, New Jersey, 08724

  • Bristol Regional Medical Center

    Bristol, Tennessee, 37620

  • Wellmont Medical Associates Oncology and Hematology-Bristol

    Bristol, Tennessee, 37620

  • Ballad Health Cancer Care - Bristol

    Bristol, Virginia, 24201

  • Saint Joseph Regional Cancer Center

    Bryan, Texas, 77802

  • Providence Saint Joseph Medical Center/Disney Family Cancer Center

    Burbank, California, 91505

  • Saint Anne Hospital

    Burien, Washington, 98166

  • Lahey Clinic

    Burlington, Massachusetts, 01805

  • Aurora Cancer Care-Southern Lakes VLCC

    Burlington, Wisconsin, 53105

  • Fairview Ridges Hospital

    Burnsville, Minnesota, 55337

  • Saint James Community Hospital and Cancer Treatment Center

    Butte, Montana, 59701

  • Saint Alphonsus Cancer Care Center-Caldwell

    Caldwell, Idaho, 83605

  • Illinois CancerCare-Canton

    Canton, Illinois, 61520

  • Mercy Cancer Center - Cape Girardeau

    Cape Girardeau, Missouri, 63703

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • Memorial Hospital of Carbondale

    Carbondale, Illinois, 62902

  • Carson Tahoe Regional Medical Center

    Carson City, Nevada, 89703

  • SIH Cancer Institute

    Carterville, Illinois, 62918

  • Illinois CancerCare-Carthage

    Carthage, Illinois, 62321

  • Sandra L Maxwell Cancer Center

    Cedar City, Utah, 84720

  • Dayton Physicians LLC-Miami Valley South

    Centerville, Ohio, 45459

  • Miami Valley Hospital South

    Centerville, Ohio, 45459

  • Centralia Oncology Clinic

    Centralia, Illinois, 62801

  • Providence Regional Cancer System-Centralia

    Centralia, Washington, 98531

  • Christiana Care Health System-Concord Health Center

    Chadds Ford, Pennsylvania, 19317

  • Cancer Center of Kansas - Chanute

    Chanute, Kansas, 66720

  • Roper Hospital

    Charleston, South Carolina, 29401

  • Charleston Oncology - Roper

    Charleston, South Carolina, 29403

  • Lowcountry Hematology Oncology PA-North Charleston

    Charleston, South Carolina, 29406

  • Bon Secours Saint Francis Hospital

    Charleston, South Carolina, 29414

  • Charleston Oncology - Saint Francis

    Charleston, South Carolina, 29414

  • Lowcountry Oncology Associates - West Ashley

    Charleston, South Carolina, 29414

  • Novant Health Presbyterian Medical Center

    Charlotte, North Carolina, 28204

  • Novant Health Carolina Surgical - Randolph

    Charlotte, North Carolina, 28207

  • Oncology Specialists of Charlotte

    Charlotte, North Carolina, 28207

  • Southern Oncology Specialists-Charlotte

    Charlotte, North Carolina, 28262

  • Memorial Hospital

    Chattanooga, Tennessee, 37404

  • Cheyenne Regional Medical Center-West

    Cheyenne, Wyoming, 82001

  • Adena Regional Medical Center

    Chillicothe, Ohio, 45601

  • Oncology Hematology Care Inc-Eden Park

    Cincinnati, Ohio, 45202

  • Oncology Hematology Care Inc-Mercy West

    Cincinnati, Ohio, 45211

  • University of Cincinnati Cancer Center-UC Medical Center

    Cincinnati, Ohio, 45219

  • Good Samaritan Hospital - Cincinnati

    Cincinnati, Ohio, 45220

  • Oncology Hematology Care Inc-Anderson

    Cincinnati, Ohio, 45230

  • Oncology Hematology Care Inc-Kenwood

    Cincinnati, Ohio, 45236

  • Bethesda North Hospital

    Cincinnati, Ohio, 45242

  • Oncology Hematology Care Inc-Blue Ash

    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

  • Sampson Radiation Oncology

    Clinton, North Carolina, 28328

  • Southeastern Medical Oncology Center-Clinton

    Clinton, North Carolina, 28328

  • Mercy Cancer Center-West Lakes

    Clive, Iowa, 50325

  • UI Health Care Mission Cancer and Blood - West Des Moines Clinic

    Clive, Iowa, 50325

  • AdventHealth Infusion Center Haywood

    Clyde, North Carolina, 28721

  • Big Horn Basin Cancer Center

    Cody, Wyoming, 82414

  • Billings Clinic-Cody

    Cody, Wyoming, 82414

  • Kootenai Health - Coeur d'Alene

    Coeur d'Alene, Idaho, 83814

  • Coffeyville Regional Medical Center

    Coffeyville, Kansas, 67337

  • Penrose-Saint Francis Healthcare

    Colorado Springs, Colorado, 80907

  • Rocky Mountain Cancer Centers-Penrose

    Colorado Springs, Colorado, 80907

  • MU Health - University Hospital/Ellis Fischel Cancer Center

    Columbia, Missouri, 65212

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Columbus Oncology and Hematology Associates Inc

    Columbus, Ohio, 43214

  • Riverside Methodist Hospital

    Columbus, Ohio, 43214

  • Grant Medical Center

    Columbus, Ohio, 43215

  • The Mark H Zangmeister Center

    Columbus, Ohio, 43219

  • Mount Carmel Health Center West

    Columbus, Ohio, 43222

  • Doctors Hospital

    Columbus, Ohio, 43228

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • Bay Area Hospital

    Coos Bay, Oregon, 97420

  • Baptist Health Corbin

    Corbin, Kentucky, 40701

  • Commonwealth Cancer Center-Corbin

    Corbin, Kentucky, 40701

  • Alegent Health Mercy Hospital

    Council Bluffs, Iowa, 51503

  • Greater Regional Medical Center

    Creston, Iowa, 50801

  • Oncology Hematology Care Inc-Crestview

    Crestview Hills, Kentucky, 41017

  • Carle at The Riverfront

    Danville, Illinois, 61832

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • MercyOne Genesis Davenport Medical Center

    Davenport, Iowa, 52803

  • MercyOne Genesis Davenport Cancer Center

    Davenport, Iowa, 52804

  • Iowa Cancer Specialists

    Davenport, Iowa, 52807

  • Good Samaritan Hospital - Dayton

    Dayton, Ohio, 45406

  • Miami Valley Hospital

    Dayton, Ohio, 45409

  • Dayton Physician LLC - Englewood

    Dayton, Ohio, 45415

  • Miami Valley Hospital North

    Dayton, Ohio, 45415

  • Corewell Health Dearborn Hospital

    Dearborn, Michigan, 48124

  • Cancer Care Specialists of Illinois - Decatur

    Decatur, Illinois, 62526

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Delaware Health Center-Grady Cancer Center

    Delaware, Ohio, 43015

  • Delaware Radiation Oncology

    Delaware, Ohio, 43015

  • Grady Memorial Hospital

    Delaware, Ohio, 43015

  • Denver Health Medical Center

    Denver, Colorado, 80204

  • Kaiser Permanente-Franklin

    Denver, Colorado, 80205

  • The Women's Imaging Center

    Denver, Colorado, 80209

  • AdventHealth Porter

    Denver, Colorado, 80210

  • Colorado Blood Cancer Institute

    Denver, Colorado, 80218

  • Presbyterian - Saint Lukes Medical Center - Health One

    Denver, Colorado, 80218

  • Rocky Mountain Cancer Centers-Midtown

    Denver, Colorado, 80218

  • Saint Joseph Hospital - Cancer Centers of Colorado

    Denver, Colorado, 80218

  • Rocky Mountain Cancer Centers-Rose

    Denver, Colorado, 80220

  • Rose Medical Center

    Denver, Colorado, 80220

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • UI Health Care Mission Cancer and Blood - Des Moines Clinic

    Des Moines, Iowa, 50309

  • Broadlawns Medical Center

    Des Moines, Iowa, 50314

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • UI Health Care Mission Cancer and Blood - Laurel Clinic

    Des Moines, Iowa, 50314

  • Iowa Lutheran Hospital

    Des Moines, Iowa, 50316

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Cancer Center of Kansas - Dodge City

    Dodge City, Kansas, 67801

  • Epic Care-Dublin

    Dublin, California, 94568

  • Essentia Health Cancer Center

    Duluth, Minnesota, 55805

  • Essentia Health Saint Mary's Medical Center

    Duluth, Minnesota, 55805

  • Miller-Dwan Hospital

    Duluth, Minnesota, 55805

  • CommonSpirit Cancer Center Mercy

    Durango, Colorado, 81301

  • Mercy Medical Center

    Durango, Colorado, 81301

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

  • Swedish Cancer Institute-Edmonds

    Edmonds, Washington, 98026

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • Crossroads Cancer Center

    Effingham, Illinois, 62401

  • Cancer Center of Kansas - El Dorado

    El Dorado, Kansas, 67042

  • Baptist Health Hardin

    Elizabethtown, Kentucky, 42701

  • Bay Area Breast Surgeons Inc

    Emeryville, California, 94608

  • Epic Care Partners in Cancer Care

    Emeryville, California, 94608

  • Walter Knox Memorial Hospital

    Emmett, Idaho, 83617

  • Newman Regional Health

    Emporia, Kansas, 66801

  • Mountain Blue Cancer Care Center - Swedish

    Englewood, Colorado, 80113

  • Swedish Medical Center

    Englewood, Colorado, 80113

  • Saint Elizabeth Hospital

    Enumclaw, Washington, 98022

  • Illinois CancerCare-Eureka

    Eureka, Illinois, 61530

  • NorthShore University HealthSystem-Evanston Hospital

    Evanston, Illinois, 60201

  • Deaconess Clinic Downtown

    Evansville, Indiana, 47713

  • Providence Regional Cancer Partnership

    Everett, Washington, 98201

  • Fairbanks Memorial Hospital

    Fairbanks, Alaska, 99701

  • Oncology Hematology Care Inc-Healthplex

    Fairfield, Ohio, 45014

  • Essentia Health Cancer Center-South University Clinic

    Fargo, North Dakota, 58103

  • Farmington Health Center

    Farmington, Utah, 84025

  • Weisberg Cancer Treatment Center

    Farmington Hills, Michigan, 48334

  • Corewell Health Farmington Hills Hospital

    Farmington Hills, Michigan, 48336

  • Virginia Mason Federal Way Medical Center

    Federal Way, Washington, 98002

  • Saint Francis Hospital

    Federal Way, Washington, 98003

  • Lake Region Healthcare Corporation-Cancer Care

    Fergus Falls, Minnesota, 56537

  • Armes Family Cancer Center

    Findlay, Ohio, 45840

  • Blanchard Valley Hospital

    Findlay, Ohio, 45840

  • Orion Cancer Care

    Findlay, Ohio, 45840

  • Aurora Health Center-Fond du Lac

    Fond du Lac, Wisconsin, 54937

  • Kaiser Permanente-Fontana

    Fontana, California, 92335

  • Poudre Valley Hospital

    Fort Collins, Colorado, 80524

  • McFarland Clinic - Trinity Cancer Center

    Fort Dodge, Iowa, 50501

  • UI Healthcare Mission Cancer and Blood - Fort Dodge

    Fort Dodge, Iowa, 50501

  • Holy Cross Hospital

    Fort Lauderdale, Florida, 33308

  • Cancer Center of Kansas - Fort Scott

    Fort Scott, Kansas, 66701

  • Mercy Hospital Fort Smith

    Fort Smith, Arkansas, 72903

  • Atrium Medical Center-Middletown Regional Hospital

    Franklin, Ohio, 45005-1066

  • Dayton Physicians LLC-Atrium

    Franklin, Ohio, 45005

  • Kaiser Permanente-Fremont

    Fremont, California, 94538

  • Kaiser Permanente-Fresno

    Fresno, California, 93720

  • Unity Hospital

    Fridley, Minnesota, 55432

  • Saint Luke's Cancer Institute - Fruitland

    Fruitland, Idaho, 83619

  • Gibbs Cancer Center-Gaffney

    Gaffney, South Carolina, 29341

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

  • Illinois CancerCare-Galesburg

    Galesburg, Illinois, 61401

  • Western Illinois Cancer Treatment Center

    Galesburg, Illinois, 61401

  • Central Care Cancer Center - Garden City

    Garden City, Kansas, 67846

  • Saint Catherine Hospital

    Garden City, Kansas, 67846

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois, 60134

  • Aurora Health Care Germantown Health Center

    Germantown, Wisconsin, 53022

  • Tacoma/Valley Radiation Oncology Centers-Gig Harbor

    Gig Harbor, Washington, 98332

  • MultiCare Gig Harbor Medical Park

    Gig Harbor, Washington, 98335

  • NorthShore University HealthSystem-Glenbrook Hospital

    Glenview, Illinois, 60026

  • Mountain Blue Cancer Care Center

    Golden, Colorado, 80401

  • National Jewish Health-Western Hematology Oncology

    Golden, Colorado, 80401

  • Southeastern Medical Oncology Center-Goldsboro

    Goldsboro, North Carolina, 27534

  • Wayne Memorial Hospital

    Goldsboro, North Carolina, 27534

  • Wayne Radiation Oncology

    Goldsboro, North Carolina, 27534

  • Aurora Cancer Care-Grafton

    Grafton, Wisconsin, 53024

  • Nebraska Cancer Specialists/Oncology Hematology West PC

    Grand Island, Nebraska, 68803

  • Saint Mary's Hospital and Regional Medical Center

    Grand Junction, Colorado, 81501

  • Grand Valley Oncology

    Grand Junction, Colorado, 81505

  • Corewell Health Grand Rapids Hospitals - Butterworth Hospital

    Grand Rapids, Michigan, 49503

  • Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

    Grand Rapids, Michigan, 49503

  • Trinity Health Grand Rapids Hospital

    Grand Rapids, Michigan, 49503

  • Central Care Cancer Center - Great Bend

    Great Bend, Kansas, 67530

  • Saint Rose Ambulatory and Surgery Center

    Great Bend, Kansas, 67530

  • Benefis Sletten Cancer Institute

    Great Falls, Montana, 59405

  • Great Falls Clinic

    Great Falls, Montana, 59405

  • Banner North Colorado Medical Center

    Greeley, Colorado, 80631

  • Aurora BayCare Medical Center

    Green Bay, Wisconsin, 54311

  • UPMC Cancer Centers - Arnold Palmer Pavilion

    Greensburg, Pennsylvania, 15601

  • Dayton Physicians LLC-Wayne

    Greenville, Ohio, 45331

  • Wayne Hospital

    Greenville, Ohio, 45331

  • Saint Francis Hospital

    Greenville, South Carolina, 29601

  • Saint Francis Cancer Center

    Greenville, South Carolina, 29607

  • Rocky Mountain Cancer Centers-Greenwood Village

    Greenwood Village, Colorado, 80111

  • Gibbs Cancer Center-Pelham

    Greer, South Carolina, 29651

  • William Beaumont Hospital-Grosse Pointe

    Grosse Pointe, Michigan, 48230

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Kaiser Permanente South Bay

    Harbor City, California, 90710

  • HaysMed

    Hays, Kansas, 67601

  • Geisinger Medical Center-Cancer Center Hazleton

    Hazleton, Pennsylvania, 18201

  • Saint Peter's Community Hospital

    Helena, Montana, 59601

  • Cancer and Blood Specialists-Henderson

    Henderson, Nevada, 89052

  • Comprehensive Cancer Centers of Nevada - Henderson

    Henderson, Nevada, 89052

  • Comprehensive Cancer Centers of Nevada-Horizon Ridge

    Henderson, Nevada, 89052

  • Las Vegas Cancer Center-Henderson

    Henderson, Nevada, 89052

  • Comprehensive Cancer Centers of Nevada-Southeast Henderson

    Henderson, Nevada, 89074

  • Oncology Las Vegas - Henderson

    Henderson, Nevada, 89074

  • Margaret R Pardee Memorial Hospital

    Hendersonville, North Carolina, 28791

  • AdventHealth Hendersonville

    Hendersonville, North Carolina, 28792

  • NorthShore University HealthSystem-Highland Park Hospital

    Highland Park, Illinois, 60035

  • Pulmonary Medicine Center of Chattanooga-Hixson

    Hixson, Tennessee, 37343

  • Bayshore Community Hospital

    Holmdel, New Jersey, 07733

  • Hawaii Cancer Care Inc - Waterfront Plaza

    Honolulu, Hawaii, 96813

  • Island Urology

    Honolulu, Hawaii, 96813

  • Queen's Cancer Cenrer - POB I

    Honolulu, Hawaii, 96813

  • Queen's Medical Center

    Honolulu, Hawaii, 96813

  • Straub Clinic and Hospital

    Honolulu, Hawaii, 96813

  • University of Hawaii Cancer Center

    Honolulu, Hawaii, 96813

  • Hawaii Cancer Care Inc-Liliha

    Honolulu, Hawaii, 96817

  • Kuakini Medical Center

    Honolulu, Hawaii, 96817

  • Queen's Cancer Center - Kuakini

    Honolulu, Hawaii, 96817

  • The Cancer Center of Hawaii-Liliha

    Honolulu, Hawaii, 96817

  • Kaiser Permanente Moanalua Medical Center

    Honolulu, Hawaii, 96819

  • Kapiolani Medical Center for Women and Children

    Honolulu, Hawaii, 96826

Other trials in United States

About this study

Official title: A Randomized Phase II Trial of Intermittent Versus Continuous Dosing of Dabrafenib (NSC-763760) and Trametinib (NSC-763093) in BRAF V600E/K Mutant Melanoma

This phase II trial compares the effect of dabrafenib and trametinib given continuously to given with a break in treatment (intermittent) in treating patients with stage III-IV melanoma that cannot be removed by surgery and contains a B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutation. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving dabrafenib and trametinib with intermittent dosing may be as effect as when given continuously in treating patients with stage III-IV melanoma with a BRAF mutation that cannot be removed by surgery.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To compare progression-free survival with intermittent dosing and continuous dosing of dabrafenib and trametinib among patients with metastatic BRAF V600E/K mutant melanoma.

SECONDARY OBJECTIVES:

  1. To estimate the frequency and severity of toxicities of the two dosing schedules.

II. To compare the frequency and severity of fever >= grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) 4.0 of the two dosing schedules.

III. To compare the response rate (complete and partial response, confirmed and unconfirmed), overall survival, and survival after progression between the two dosing schedules on step 2.

TRANSLATIONAL MEDICINE OBJECTIVES:

  1. To evaluate whether acquired molecular events leading to reactivation of the MAPK pathway are more common among patients on the continuous dosing arm than on the intermittent dosing arm using circulating tumor deoxyribonucleic acid (DNA) (ctDNA).

II. To assess the prognostic association between baseline biomarkers and early molecular events with progression free survival (PFS).

III. To explore the potential interaction between treatment arm and baseline biomarkers/early molecular events with PFS.

IV. To bank tissue and whole blood in anticipation of future studies to evaluate molecular events associated with clinical benefit and disease progression in patients treated with continuous versus intermittent dabrafenib and trametinib.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I (CONTINUOUS DOSING): Patients receive dabrafenib orally (PO) twice daily (BID) and trametinib PO once daily (QD) on days 1-56 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients also undergo positron emission tomography/computed tomography (PET/CT) or CT scans in week 1 of cycle 2 and at off treatment follow up prior to progression. Additionally, patients undergo blood sample collection, echocardiography (ECHO) or multigated acquisition scan (MUGA) on study.

ARM II (INTERMITTENT DOSING): Patients receive dabrafenib PO BID and trametinib PO QD on days 1-7 and 29-56 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT or CT scans in week 1 of cycle 2 and at off treatment follow up prior to progression. Additionally, patients undergo blood sample collection, ECHO or MUGA on study.

After completion of study treatment, patients are followed up every 6 months for 3 years and then yearly for 2 years.

Being tested
Biospecimen Collection, Computed Tomography, Dabrafenib Mesylate, Echocardiography Test, Multigated Acquisition Scan
Medical subject headings
Melanoma

What participants receive

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

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT or PET/CT

  • Dabrafenib MesylateDrug

    Also called Dabrafenib Methanesulfonate, GSK2118436 Methane Sulfonate Salt, GSK2118436B, Tafinlar

    Given PO

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography

    Undergo ECHO

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan

    Undergo MUGA

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET/CT

  • Trametinib Dimethyl SulfoxideDrug

    Also called Mekinist, Meqsel, Spexotras

    Given PO

Study groups in NCT02196181
Study groupRoleWhat they receive
Arm I (continuous dosing)ExperimentalPatients receive dabrafenib PO BID and trametinib PO QD on days 1-56 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT or CT scans in week 1 of cycle 2 and at off treatment follow up prior to progression. Additionally, patients undergo blood sample collection, ECHO or MUGA on study.
Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Dabrafenib Mesylate; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Procedure: Positron Emission Tomography; Drug: Trametinib Dimethyl Sulfoxide
Arm II (intermittent dosing)ExperimentalPatients receive dabrafenib PO BID and trametinib PO QD on days 1-7 and 29-56 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT or CT scans in week 1 of cycle 2 and at off treatment follow up prior to progression. Additionally, patients undergo blood sample collection, ECHO or MUGA on study.
Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Dabrafenib Mesylate; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Procedure: Positron Emission Tomography; Drug: Trametinib Dimethyl Sulfoxide

What is being measured

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

  1. Progression-free survival (PFS)

    Testing of the superiority of intermittent dosing of dabrafenib and trametinib compared to continuous dosing with these two same agents will be based on progression-free survival. Stratified Cox regression models stratified by stratification factors will be used for all analyses.

    Measured: Measured from date of randomization, assessed up to 5 years

Secondary outcomes (3)

  1. Overall survival

    Overall survival between patients on each arm and survival after progression will be compared using Cox regression models.

    Measured: Up to 5 years

  2. Response rates

    Response rates between arms will be compared using Fisher's exact test.

    Measured: Up to 5 years

  3. Rates of fever

    Defined as >= grade 3 per Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0 with attribution possibly, probably, or definitely related to treatment; or any >= grade 1 per CTCAE v4.0 with attribution possibly, probably, or definitely related to treatment with chills, dehydration, hypotension, dizziness, or muscle weakness per CTCAE v4.0 with attribution possibly, probably, or definitely related to treatment reported during the same course. Rates of fever between arms will also be compared using Fisher's exact test.

    Measured: Up to 5 years

Timeline

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

  1. First posted21 Jul 2014 (estimated)
  2. Study start19 Sep 2014
  3. Primary completion15 Mar 2027 (estimated)
  4. Study completion15 Mar 2027 (estimated)

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
None (open label)
Enrolment
280 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02196181
Sponsor's protocol ID
NCI-2014-01470
Other IDs
NCI-2014-01470, S1320, S1320, U10CA032102, U10CA180888
Status last verified
Sep 2026
First submitted
18 Jul 2014
Last updated
22 Oct 2026
Results posted
No
Data monitoring committee
No

Publications

  • Wang Y, Liu S, Yang Z, Algazi AP, Lomeli SH, Wang Y, Othus M, Hong A, Wang X, Randolph CE, Jones AM, Bosenberg MW, Byrum SD, Tackett AJ, Lopez H, Yates C, Solit DB, Ribas A, Piva M, Moriceau G, Lo RS. Anti-PD-1/L1 lead-in before MAPK inhibitor combination maximizes antitumor immunity and efficacy. Cancer Cell. 2021 Oct 11;39(10):1375-1387.e6. doi: 10.1016/j.ccell.2021.07.023. Epub 2021 Aug 19.

    PubMed 34416167

  • Algazi AP, Othus M, Daud AI, Lo RS, Mehnert JM, Truong TG, Conry R, Kendra K, Doolittle GC, Clark JI, Messino MJ, Moore DF Jr, Lao C, Faller BA, Govindarajan R, Harker-Murray A, Dreisbach L, Moon J, Grossmann KF, Ribas A. Continuous versus intermittent BRAF and MEK inhibition in patients with BRAF-mutated melanoma: a randomized phase 2 trial. Nat Med. 2020 Oct;26(10):1564-1568. doi: 10.1038/s41591-020-1060-8. Epub 2020 Oct 5.

    PubMed 33020646

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