Prueba de dabrafenib y trametinib con o sin hidroxicloroquina en el melanoma BRAF V600E/K en estadio IIIC o IV
El estudio BAMM2 (BRAF, autofagia, inhibición de MEK en melanoma): un estudio aleatorizado doble ciego de fase II de dabrafenib y trametinib con o sin hidroxicloroquina en melanoma avanzado BRAF V600E/K
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.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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Alaska
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Anchorage, Alaska, Estados Unidos, 98508
- Anchorage Associates in Radiation Medicine
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Anchorage, Alaska, Estados Unidos, 99508
- Alaska Breast Care and Surgery LLC
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Anchorage, Alaska, Estados Unidos, 99508
- Alaska Oncology and Hematology LLC
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Anchorage, Alaska, Estados Unidos, 99508
- Alaska Women's Cancer Care
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Anchorage, Alaska, Estados Unidos, 99508
- Anchorage Oncology Centre
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Anchorage, Alaska, Estados Unidos, 99508
- Katmai Oncology Group
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Anchorage, Alaska, Estados Unidos, 99508
- Providence Alaska Medical Center
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Anchorage, Alaska, Estados Unidos, 99504
- Anchorage Radiation Therapy Center
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Arizona
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Phoenix, Arizona, Estados Unidos, 85054
- Mayo Clinic Hospital in Arizona
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Phoenix, Arizona, Estados Unidos, 85004
- Cancer Center at Saint Joseph's
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Scottsdale, Arizona, Estados Unidos, 85259
- Mayo Clinic in Arizona
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Arkansas
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Fort Smith, Arkansas, Estados Unidos, 72903
- Mercy Hospital Fort Smith
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Hot Springs, Arkansas, Estados Unidos, 71913
- CHI Saint Vincent Cancer Center Hot Springs
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California
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Arroyo Grande, California, Estados Unidos, 93420
- Mission Hope Medical Oncology - Arroyo Grande
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Burbank, California, Estados Unidos, 91505
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
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Los Angeles, California, Estados Unidos, 90048
- Cedars Sinai Medical Center
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San Luis Obispo, California, Estados Unidos, 93401
- Pacific Central Coast Health Center-San Luis Obispo
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Santa Maria, California, Estados Unidos, 93444
- Mission Hope Medical Oncology - Santa Maria
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Colorado
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Colorado Springs, Colorado, Estados Unidos, 80907
- Penrose-Saint Francis Healthcare
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Colorado Springs, Colorado, Estados Unidos, 80907
- Rocky Mountain Cancer Centers-Penrose
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Colorado Springs, Colorado, Estados Unidos, 80923
- Saint Francis Cancer Center
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Denver, Colorado, Estados Unidos, 80210
- Porter Adventist Hospital
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Durango, Colorado, Estados Unidos, 81301
- Mercy Medical Center
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Durango, Colorado, Estados Unidos, 81301
- Southwest Oncology PC
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Lakewood, Colorado, Estados Unidos, 80228
- Saint Anthony Hospital
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Littleton, Colorado, Estados Unidos, 80122
- Littleton Adventist Hospital
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Longmont, Colorado, Estados Unidos, 80501
- Longmont United Hospital
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Longmont, Colorado, Estados Unidos, 80501
- Rocky Mountain Cancer Centers-Longmont
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Parker, Colorado, Estados Unidos, 80138
- Parker Adventist Hospital
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Pueblo, Colorado, Estados Unidos, 81004
- Saint Mary Corwin Medical Center
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Delaware
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Frankford, Delaware, Estados Unidos, 19945
- Beebe South Coastal Health Campus
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Lewes, Delaware, Estados Unidos, 19958
- Beebe Medical Center
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Newark, Delaware, Estados Unidos, 19713
- Helen F Graham Cancer Center
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Newark, Delaware, Estados Unidos, 19713
- Delaware Clinical and Laboratory Physicians PA
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Newark, Delaware, Estados Unidos, 19713
- Medical Oncology Hematology Consultants PA
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Newark, Delaware, Estados Unidos, 19718
- Christiana Care Health System-Christiana Hospital
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Rehoboth Beach, Delaware, Estados Unidos, 19971
- Beebe Health Campus
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Seaford, Delaware, Estados Unidos, 19973
- TidalHealth Nanticoke / Allen Cancer Center
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Wilmington, Delaware, Estados Unidos, 19801
- Christiana Care Health System-Wilmington Hospital
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District of Columbia
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Washington D.C., District of Columbia, Estados Unidos, 20007
- MedStar Georgetown University Hospital
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Florida
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Aventura, Florida, Estados Unidos, 33180
- UM Sylvester Comprehensive Cancer Center at Aventura
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Coral Gables, Florida, Estados Unidos, 33146
- UM Sylvester Comprehensive Cancer Center at Coral Gables
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Deerfield Beach, Florida, Estados Unidos, 33442
- UM Sylvester Comprehensive Cancer Center at Deerfield Beach
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Miami, Florida, Estados Unidos, 33136
- University of Miami Miller School of Medicine-Sylvester Cancer Center
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Miami, Florida, Estados Unidos, 33176
- UM Sylvester Comprehensive Cancer Center at Kendall
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Plantation, Florida, Estados Unidos, 33324
- UM Sylvester Comprehensive Cancer Center at Plantation
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Idaho
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Boise, Idaho, Estados Unidos, 83712
- Saint Luke's Cancer Institute - Boise
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Fruitland, Idaho, Estados Unidos, 83619
- Saint Luke's Cancer Institute - Fruitland
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Meridian, Idaho, Estados Unidos, 83642
- Saint Luke's Cancer Institute - Meridian
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Nampa, Idaho, Estados Unidos, 83686
- Saint Luke's Cancer Institute - Nampa
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Twin Falls, Idaho, Estados Unidos, 83301
- Saint Luke's Cancer Institute - Twin Falls
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Illinois
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Alton, Illinois, Estados Unidos, 62002
- Saint Anthony's Health
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Aurora, Illinois, Estados Unidos, 60504
- Rush - Copley Medical Center
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Burr Ridge, Illinois, Estados Unidos, 60527
- Loyola Center for Health at Burr Ridge
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Danville, Illinois, Estados Unidos, 61832
- Carle on Vermilion
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Effingham, Illinois, Estados Unidos, 62401
- Carle Physician Group-Effingham
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Homer Glen, Illinois, Estados Unidos, 60491
- Loyola Medicine Homer Glen
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Mattoon, Illinois, Estados Unidos, 61938
- Carle Physician Group-Mattoon/Charleston
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Maywood, Illinois, Estados Unidos, 60153
- Loyola University Medical Center
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Melrose Park, Illinois, Estados Unidos, 60160
- Marjorie Weinberg Cancer Center at Loyola-Gottlieb
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Mount Vernon, Illinois, Estados Unidos, 62864
- Good Samaritan Regional Health Center
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Urbana, Illinois, Estados Unidos, 61801
- Carle Cancer Center
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Urbana, Illinois, Estados Unidos, 61801
- The Carle Foundation Hospital
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Yorkville, Illinois, Estados Unidos, 60560
- Rush-Copley Healthcare Center
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Indiana
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Richmond, Indiana, Estados Unidos, 47374
- Reid Health
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Iowa
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Ames, Iowa, Estados Unidos, 50010
- McFarland Clinic PC - Ames
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Ames, Iowa, Estados Unidos, 50010
- Mary Greeley Medical Center
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Boone, Iowa, Estados Unidos, 50036
- McFarland Clinic PC-Boone
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Carroll, Iowa, Estados Unidos, 51401
- Saint Anthony Regional Hospital
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Clive, Iowa, Estados Unidos, 50325
- Mercy Cancer Center-West Lakes
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Clive, Iowa, Estados Unidos, 50325
- Medical Oncology and Hematology Associates-West Des Moines
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Council Bluffs, Iowa, Estados Unidos, 51503
- Alegent Health Mercy Hospital
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Creston, Iowa, Estados Unidos, 50801
- Greater Regional Medical Center
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Des Moines, Iowa, Estados Unidos, 50309
- Iowa Methodist Medical Center
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Des Moines, Iowa, Estados Unidos, 50314
- Mercy Medical Center - Des Moines
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Des Moines, Iowa, Estados Unidos, 50309
- Medical Oncology and Hematology Associates-Des Moines
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Des Moines, Iowa, Estados Unidos, 50314
- Broadlawns Medical Center
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Des Moines, Iowa, Estados Unidos, 50314
- Mission Cancer and Blood - Laurel
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Des Moines, Iowa, Estados Unidos, 50316
- Iowa Lutheran Hospital
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Fort Dodge, Iowa, Estados Unidos, 50501
- McFarland Clinic PC-Trinity Cancer Center
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Fort Dodge, Iowa, Estados Unidos, 50501
- Trinity Regional Medical Center
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Jefferson, Iowa, Estados Unidos, 50129
- McFarland Clinic PC-Jefferson
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Marshalltown, Iowa, Estados Unidos, 50158
- McFarland Clinic PC-Marshalltown
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West Des Moines, Iowa, Estados Unidos, 50266-7700
- Methodist West Hospital
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West Des Moines, Iowa, Estados Unidos, 50266
- Mercy Medical Center-West Lakes
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Kansas
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Garden City, Kansas, Estados Unidos, 67846
- Central Care Cancer Center - Garden City
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Great Bend, Kansas, Estados Unidos, 67530
- Central Care Cancer Center - Great Bend
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Kentucky
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Bardstown, Kentucky, Estados Unidos, 40004
- Flaget Memorial Hospital
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Corbin, Kentucky, Estados Unidos, 40701
- Commonwealth Cancer Center-Corbin
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Lexington, Kentucky, Estados Unidos, 40504
- Saint Joseph Radiation Oncology Resource Center
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Lexington, Kentucky, Estados Unidos, 40509
- Saint Joseph Hospital East
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London, Kentucky, Estados Unidos, 40741
- Saint Joseph London
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Louisville, Kentucky, Estados Unidos, 40202
- Jewish Hospital
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Louisville, Kentucky, Estados Unidos, 40245
- UofL Health Medical Center Northeast
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Louisville, Kentucky, Estados Unidos, 40215
- Saints Mary and Elizabeth Hospital
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Shepherdsville, Kentucky, Estados Unidos, 40165
- Jewish Hospital Medical Center South
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Maryland
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Baltimore, Maryland, Estados Unidos, 21237
- MedStar Franklin Square Medical Center/Weinberg Cancer Institute
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Minnesota
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Rochester, Minnesota, Estados Unidos, 55905
- Mayo Clinic in Rochester
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Missouri
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Ballwin, Missouri, Estados Unidos, 63011
- Saint Louis Cancer and Breast Institute-Ballwin
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Bolivar, Missouri, Estados Unidos, 65613
- Central Care Cancer Center - Bolivar
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Branson, Missouri, Estados Unidos, 65616
- Cox Cancer Center Branson
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Joplin, Missouri, Estados Unidos, 64804
- Freeman Health System
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Joplin, Missouri, Estados Unidos, 64804
- Mercy Hospital Joplin
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Rolla, Missouri, Estados Unidos, 65401
- Delbert Day Cancer Institute at PCRMC
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Rolla, Missouri, Estados Unidos, 65401
- Mercy Clinic-Rolla-Cancer and Hematology
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Saint Joseph, Missouri, Estados Unidos, 64506
- Heartland Regional Medical Center
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Springfield, Missouri, Estados Unidos, 65807
- CoxHealth South Hospital
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Springfield, Missouri, Estados Unidos, 65804
- Mercy Hospital Springfield
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St Louis, Missouri, Estados Unidos, 63141
- Mercy Hospital Saint Louis
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St Louis, Missouri, Estados Unidos, 63128
- Mercy Hospital South
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St Louis, Missouri, Estados Unidos, 63109
- Saint Louis Cancer and Breast Institute-South City
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Washington, Missouri, Estados Unidos, 63090
- Mercy Hospital Washington
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Montana
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Missoula, Montana, Estados Unidos, 59802
- Saint Patrick Hospital - Community Hospital
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Nebraska
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Grand Island, Nebraska, Estados Unidos, 68803
- CHI Health Saint Francis
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Kearney, Nebraska, Estados Unidos, 68847
- CHI Health Good Samaritan
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Lincoln, Nebraska, Estados Unidos, 68510
- Saint Elizabeth Regional Medical Center
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Omaha, Nebraska, Estados Unidos, 68124
- Alegent Health Bergan Mercy Medical Center
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Omaha, Nebraska, Estados Unidos, 68122
- Alegent Health Immanuel Medical Center
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Omaha, Nebraska, Estados Unidos, 68130
- Alegent Health Lakeside Hospital
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Omaha, Nebraska, Estados Unidos, 68131
- Creighton University Medical Center
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Papillion, Nebraska, Estados Unidos, 68046
- Midlands Community Hospital
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New York
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New York, New York, Estados Unidos, 10016
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
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Ohio
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Beavercreek, Ohio, Estados Unidos, 45431
- Indu and Raj Soin Medical Center
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Boardman, Ohio, Estados Unidos, 44512
- Saint Elizabeth Boardman Hospital
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Centerville, Ohio, Estados Unidos, 45459
- Miami Valley Hospital South
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Centerville, Ohio, Estados Unidos, 45459
- Dayton Physicians LLC-Miami Valley South
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Cincinnati, Ohio, Estados Unidos, 45220
- Good Samaritan Hospital - Cincinnati
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Cincinnati, Ohio, Estados Unidos, 45242
- Bethesda North Hospital
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Cincinnati, Ohio, Estados Unidos, 45236
- Oncology Hematology Care Inc-Kenwood
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Cincinnati, Ohio, Estados Unidos, 45247
- TriHealth Cancer Institute-Westside
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Cincinnati, Ohio, Estados Unidos, 45255
- TriHealth Cancer Institute-Anderson
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Dayton, Ohio, Estados Unidos, 45409
- Miami Valley Hospital
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Dayton, Ohio, Estados Unidos, 45415
- Dayton Physician LLC-Miami Valley Hospital North
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Dayton, Ohio, Estados Unidos, 45415
- Miami Valley Hospital North
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Findlay, Ohio, Estados Unidos, 45840
- Blanchard Valley Hospital
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Findlay, Ohio, Estados Unidos, 45840
- Armes Family Cancer Center
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Findlay, Ohio, Estados Unidos, 45840
- Orion Cancer Care
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Franklin, Ohio, Estados Unidos, 45005-1066
- Atrium Medical Center-Middletown Regional Hospital
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Franklin, Ohio, Estados Unidos, 45005
- Dayton Physicians LLC-Atrium
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Greenville, Ohio, Estados Unidos, 45331
- Wayne Hospital
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Greenville, Ohio, Estados Unidos, 45331
- Dayton Physicians LLC-Wayne
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Kettering, Ohio, Estados Unidos, 45429
- Kettering Medical Center
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Kettering, Ohio, Estados Unidos, 45409
- Greater Dayton Cancer Center
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Springfield, Ohio, Estados Unidos, 45505
- Springfield Regional Medical Center
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Springfield, Ohio, Estados Unidos, 45504
- Springfield Regional Cancer Center
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Troy, Ohio, Estados Unidos, 45373
- Upper Valley Medical Center
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Troy, Ohio, Estados Unidos, 45373
- Dayton Physicians LLC-Upper Valley
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Warren, Ohio, Estados Unidos, 44484
- Saint Joseph Warren Hospital
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Youngstown, Ohio, Estados Unidos, 44501
- Saint Elizabeth Youngstown Hospital
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Oklahoma
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Oklahoma City, Oklahoma, Estados Unidos, 73120
- Mercy Hospital Oklahoma City
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Oregon
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Bend, Oregon, Estados Unidos, 97701
- Saint Charles Health System
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Clackamas, Oregon, Estados Unidos, 97015
- Clackamas Radiation Oncology Center
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Clackamas, Oregon, Estados Unidos, 97015
- Providence Cancer Institute Clackamas Clinic
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Coos Bay, Oregon, Estados Unidos, 97420
- Bay Area Hospital
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Newberg, Oregon, Estados Unidos, 97132
- Providence Newberg Medical Center
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Portland, Oregon, Estados Unidos, 97213
- Providence Portland Medical Center
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Portland, Oregon, Estados Unidos, 97225
- Providence Saint Vincent Medical Center
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Redmond, Oregon, Estados Unidos, 97756
- Saint Charles Health System-Redmond
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Pennsylvania
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Chadds Ford, Pennsylvania, Estados Unidos, 19317
- Christiana Care Health System-Concord Health Center
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Philadelphia, Pennsylvania, Estados Unidos, 19104
- University of Pennsylvania/Abramson Cancer Center
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Pittsburgh, Pennsylvania, Estados Unidos, 15232
- University of Pittsburgh Cancer Institute (UPCI)
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Texas
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Bryan, Texas, Estados Unidos, 77802
- Saint Joseph Regional Cancer Center
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Utah
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Salt Lake City, Utah, Estados Unidos, 84112
- Huntsman Cancer Institute/University of Utah
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Washington
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Aberdeen, Washington, Estados Unidos, 98520
- Providence Regional Cancer System-Aberdeen
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Bellingham, Washington, Estados Unidos, 98225
- PeaceHealth Saint Joseph Medical Center
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Bremerton, Washington, Estados Unidos, 98310
- Harrison HealthPartners Hematology and Oncology-Bremerton
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Bremerton, Washington, Estados Unidos, 98310
- Harrison Medical Center
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Burien, Washington, Estados Unidos, 98166
- Highline Medical Center-Main Campus
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Centralia, Washington, Estados Unidos, 98531
- Providence Regional Cancer System-Centralia
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Edmonds, Washington, Estados Unidos, 98026
- Swedish Cancer Institute-Edmonds
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Enumclaw, Washington, Estados Unidos, 98022
- Saint Elizabeth Hospital
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Everett, Washington, Estados Unidos, 98201
- Providence Regional Cancer Partnership
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Federal Way, Washington, Estados Unidos, 98003
- Saint Francis Hospital
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Issaquah, Washington, Estados Unidos, 98029
- Swedish Cancer Institute-Issaquah
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Kennewick, Washington, Estados Unidos, 99336
- Kadlec Clinic Hematology and Oncology
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Lacey, Washington, Estados Unidos, 98503
- Providence Regional Cancer System-Lacey
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Lakewood, Washington, Estados Unidos, 98499
- Saint Clare Hospital
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Longview, Washington, Estados Unidos, 98632
- PeaceHealth Saint John Medical Center
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Poulsbo, Washington, Estados Unidos, 98370
- Harrison HealthPartners Hematology and Oncology-Poulsbo
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Seattle, Washington, Estados Unidos, 98107
- Swedish Medical Center-Ballard Campus
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Seattle, Washington, Estados Unidos, 98122
- Swedish Medical Center-First Hill
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Seattle, Washington, Estados Unidos, 98104
- Pacific Gynecology Specialists
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Seattle, Washington, Estados Unidos, 98122-5711
- Swedish Medical Center-Cherry Hill
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Sedro-Woolley, Washington, Estados Unidos, 98284
- PeaceHealth United General Medical Center
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Shelton, Washington, Estados Unidos, 98584
- Providence Regional Cancer System-Shelton
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Tacoma, Washington, Estados Unidos, 98405
- Franciscan Research Center-Northwest Medical Plaza
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Vancouver, Washington, Estados Unidos, 98664
- PeaceHealth Southwest Medical Center
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Walla Walla, Washington, Estados Unidos, 99362
- Providence Saint Mary Regional Cancer Center
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Yelm, Washington, Estados Unidos, 98597
- Providence Regional Cancer System-Yelm
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Wisconsin
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Chippewa Falls, Wisconsin, Estados Unidos, 54729
- Marshfield Clinic-Chippewa Center
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Eau Claire, Wisconsin, Estados Unidos, 54701
- Marshfield Medical Center-EC Cancer Center
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Ladysmith, Wisconsin, Estados Unidos, 54848
- Marshfield Clinic - Ladysmith Center
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Marshfield, Wisconsin, Estados Unidos, 54449
- Marshfield Medical Center-Marshfield
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Minocqua, Wisconsin, Estados Unidos, 54548
- Marshfield Clinic-Minocqua Center
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Rice Lake, Wisconsin, Estados Unidos, 54868
- Marshfield Medical Center-Rice Lake
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Stevens Point, Wisconsin, Estados Unidos, 54482
- Marshfield Medical Center-River Region at Stevens Point
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Wausau, Wisconsin, Estados Unidos, 54401
- Marshfield Clinic-Wausau Center
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Weston, Wisconsin, Estados Unidos, 54476
- Marshfield Medical Center - Weston
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Wisconsin Rapids, Wisconsin, Estados Unidos, 54494
- Marshfield Clinic - Wisconsin Rapids Center
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
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Patient must have locally advanced unresectable stage IIIC or stage IV melanoma
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Patient must have BRAF V600E or BRAF V600K tumor genotype based on a Clinical Laboratory Improvement Act (CLIA) approved assay
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Patient must have serum LDH > Upper limit of normal per institution standards
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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
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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
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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.
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Patient may have been treated with prior chemotherapy or radiation therapy
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Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
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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
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All females of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy.
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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
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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
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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
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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
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Absolute neutrophil count >= 1,500/mcL (obtained =< 14 days prior to protocol randomization)
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Platelets >= 100,000/mcL (obtained =< 14 days prior to protocol randomization)
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Total bilirubin =< institutional upper limit of normal (ULN) (obtained =< 14 days prior to protocol randomization)
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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)
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Creatinine =< 1.5 x institutional ULN (obtained =< 14 days prior to protocol randomization)
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Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
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For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
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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
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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:
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Receiving any other investigational anticancer therapy during the period on study or the 4 weeks prior to randomization
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Patients received BRAF and MEK inhibitor therapy in the metastatic setting
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Patients who are experiencing an objective partial response to immunotherapy at the time of study enrollment
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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)
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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
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Previously documented retinal vein occlusion
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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
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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
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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
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Immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study drug, or excipients or to dimethyl sulfoxide (DMSO)
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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
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Current use of a prohibited medication described in the protocol due to potential drug-drug interaction
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: 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. |
Given PO
Otros nombres:
Given PO
Otros nombres:
Given PO
Otros nombres:
|
|
Comparador activo: 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. |
Given PO Given PO
Otros nombres:
Given PO
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
One-year Progression-free Survival Rate
Periodo de tiempo: 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
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Progression-free Survival
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Ravi Amaravadi, ECOG-ACRIN Cancer Research Group
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- EA6191
- U10CA180820 (Subvención/contrato del NIH de EE. UU.)
- EA6191 (Otro identificador: CTEP)
- NCI-2020-04552 (Identificador de registro: CTRP (Clinical Trial Reporting Program))
- EA6191 (Otro identificador: ECOG-ACRIN Cancer Research Group)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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