Testování dabrafenibu a trametinibu s hydroxychlorochinem nebo bez něj ve stadiu IIIC nebo IV melanomu BRAF V600E/K
Studie BAMM2 (BRAF, autofagie, inhibice MEK u melanomu): Randomizovaná dvojitě slepá studie fáze II dabrafenibu a trametinibu s nebo bez hydroxychlorochinu u pokročilého melanomu 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.
Přehled studie
Postavení
Podmínky
Detailní popis
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.
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 2
Kontakty a umístění
Studijní místa
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Alaska
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Anchorage, Alaska, Spojené státy, 98508
- Anchorage Associates in Radiation Medicine
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Anchorage, Alaska, Spojené státy, 99508
- Alaska Breast Care and Surgery LLC
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Anchorage, Alaska, Spojené státy, 99508
- Alaska Oncology and Hematology LLC
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Anchorage, Alaska, Spojené státy, 99508
- Alaska Women's Cancer Care
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Anchorage, Alaska, Spojené státy, 99508
- Anchorage Oncology Centre
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Anchorage, Alaska, Spojené státy, 99508
- Katmai Oncology Group
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Anchorage, Alaska, Spojené státy, 99508
- Providence Alaska Medical Center
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Anchorage, Alaska, Spojené státy, 99504
- Anchorage Radiation Therapy Center
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Arizona
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Phoenix, Arizona, Spojené státy, 85054
- Mayo Clinic Hospital in Arizona
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Phoenix, Arizona, Spojené státy, 85004
- Cancer Center at Saint Joseph's
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Scottsdale, Arizona, Spojené státy, 85259
- Mayo Clinic in Arizona
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Arkansas
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Fort Smith, Arkansas, Spojené státy, 72903
- Mercy Hospital Fort Smith
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Hot Springs, Arkansas, Spojené státy, 71913
- CHI Saint Vincent Cancer Center Hot Springs
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California
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Arroyo Grande, California, Spojené státy, 93420
- Mission Hope Medical Oncology - Arroyo Grande
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Burbank, California, Spojené státy, 91505
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
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Los Angeles, California, Spojené státy, 90048
- Cedars Sinai Medical Center
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San Luis Obispo, California, Spojené státy, 93401
- Pacific Central Coast Health Center-San Luis Obispo
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Santa Maria, California, Spojené státy, 93444
- Mission Hope Medical Oncology - Santa Maria
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Colorado
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Colorado Springs, Colorado, Spojené státy, 80907
- Penrose-Saint Francis Healthcare
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Colorado Springs, Colorado, Spojené státy, 80907
- Rocky Mountain Cancer Centers-Penrose
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Colorado Springs, Colorado, Spojené státy, 80923
- Saint Francis Cancer Center
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Denver, Colorado, Spojené státy, 80210
- Porter Adventist Hospital
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Durango, Colorado, Spojené státy, 81301
- Mercy Medical Center
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Durango, Colorado, Spojené státy, 81301
- Southwest Oncology PC
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Lakewood, Colorado, Spojené státy, 80228
- Saint Anthony Hospital
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Littleton, Colorado, Spojené státy, 80122
- Littleton Adventist Hospital
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Longmont, Colorado, Spojené státy, 80501
- Longmont United Hospital
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Longmont, Colorado, Spojené státy, 80501
- Rocky Mountain Cancer Centers-Longmont
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Parker, Colorado, Spojené státy, 80138
- Parker Adventist Hospital
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Pueblo, Colorado, Spojené státy, 81004
- Saint Mary Corwin Medical Center
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Delaware
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Frankford, Delaware, Spojené státy, 19945
- Beebe South Coastal Health Campus
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Lewes, Delaware, Spojené státy, 19958
- Beebe Medical Center
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Newark, Delaware, Spojené státy, 19713
- Helen F Graham Cancer Center
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Newark, Delaware, Spojené státy, 19713
- Delaware Clinical and Laboratory Physicians PA
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Newark, Delaware, Spojené státy, 19713
- Medical Oncology Hematology Consultants PA
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Newark, Delaware, Spojené státy, 19718
- Christiana Care Health System-Christiana Hospital
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Rehoboth Beach, Delaware, Spojené státy, 19971
- Beebe Health Campus
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Seaford, Delaware, Spojené státy, 19973
- TidalHealth Nanticoke / Allen Cancer Center
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Wilmington, Delaware, Spojené státy, 19801
- Christiana Care Health System-Wilmington Hospital
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District of Columbia
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Washington D.C., District of Columbia, Spojené státy, 20007
- MedStar Georgetown University Hospital
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Florida
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Aventura, Florida, Spojené státy, 33180
- UM Sylvester Comprehensive Cancer Center at Aventura
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Coral Gables, Florida, Spojené státy, 33146
- UM Sylvester Comprehensive Cancer Center at Coral Gables
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Deerfield Beach, Florida, Spojené státy, 33442
- UM Sylvester Comprehensive Cancer Center at Deerfield Beach
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Miami, Florida, Spojené státy, 33136
- University of Miami Miller School of Medicine-Sylvester Cancer Center
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Miami, Florida, Spojené státy, 33176
- UM Sylvester Comprehensive Cancer Center at Kendall
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Plantation, Florida, Spojené státy, 33324
- UM Sylvester Comprehensive Cancer Center at Plantation
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Idaho
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Boise, Idaho, Spojené státy, 83712
- Saint Luke's Cancer Institute - Boise
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Fruitland, Idaho, Spojené státy, 83619
- Saint Luke's Cancer Institute - Fruitland
-
Meridian, Idaho, Spojené státy, 83642
- Saint Luke's Cancer Institute - Meridian
-
Nampa, Idaho, Spojené státy, 83686
- Saint Luke's Cancer Institute - Nampa
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Twin Falls, Idaho, Spojené státy, 83301
- Saint Luke's Cancer Institute - Twin Falls
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Illinois
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Alton, Illinois, Spojené státy, 62002
- Saint Anthony's Health
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Aurora, Illinois, Spojené státy, 60504
- Rush - Copley Medical Center
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Burr Ridge, Illinois, Spojené státy, 60527
- Loyola Center for Health at Burr Ridge
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Danville, Illinois, Spojené státy, 61832
- Carle on Vermilion
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Effingham, Illinois, Spojené státy, 62401
- Carle Physician Group-Effingham
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Homer Glen, Illinois, Spojené státy, 60491
- Loyola Medicine Homer Glen
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Mattoon, Illinois, Spojené státy, 61938
- Carle Physician Group-Mattoon/Charleston
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Maywood, Illinois, Spojené státy, 60153
- Loyola University Medical Center
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Melrose Park, Illinois, Spojené státy, 60160
- Marjorie Weinberg Cancer Center at Loyola-Gottlieb
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Mount Vernon, Illinois, Spojené státy, 62864
- Good Samaritan Regional Health Center
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Urbana, Illinois, Spojené státy, 61801
- Carle Cancer Center
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Urbana, Illinois, Spojené státy, 61801
- The Carle Foundation Hospital
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Yorkville, Illinois, Spojené státy, 60560
- Rush-Copley Healthcare Center
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Indiana
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Richmond, Indiana, Spojené státy, 47374
- Reid Health
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Iowa
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Ames, Iowa, Spojené státy, 50010
- McFarland Clinic PC - Ames
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Ames, Iowa, Spojené státy, 50010
- Mary Greeley Medical Center
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Boone, Iowa, Spojené státy, 50036
- McFarland Clinic PC-Boone
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Carroll, Iowa, Spojené státy, 51401
- Saint Anthony Regional Hospital
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Clive, Iowa, Spojené státy, 50325
- Mercy Cancer Center-West Lakes
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Clive, Iowa, Spojené státy, 50325
- Medical Oncology and Hematology Associates-West Des Moines
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Council Bluffs, Iowa, Spojené státy, 51503
- Alegent Health Mercy Hospital
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Creston, Iowa, Spojené státy, 50801
- Greater Regional Medical Center
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Des Moines, Iowa, Spojené státy, 50309
- Iowa Methodist Medical Center
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Des Moines, Iowa, Spojené státy, 50314
- Mercy Medical Center - Des Moines
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Des Moines, Iowa, Spojené státy, 50309
- Medical Oncology and Hematology Associates-Des Moines
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Des Moines, Iowa, Spojené státy, 50314
- Broadlawns Medical Center
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Des Moines, Iowa, Spojené státy, 50314
- Mission Cancer and Blood - Laurel
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Des Moines, Iowa, Spojené státy, 50316
- Iowa Lutheran Hospital
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Fort Dodge, Iowa, Spojené státy, 50501
- McFarland Clinic PC-Trinity Cancer Center
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Fort Dodge, Iowa, Spojené státy, 50501
- Trinity Regional Medical Center
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Jefferson, Iowa, Spojené státy, 50129
- McFarland Clinic PC-Jefferson
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Marshalltown, Iowa, Spojené státy, 50158
- McFarland Clinic PC-Marshalltown
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West Des Moines, Iowa, Spojené státy, 50266-7700
- Methodist West Hospital
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West Des Moines, Iowa, Spojené státy, 50266
- Mercy Medical Center-West Lakes
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Kansas
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Garden City, Kansas, Spojené státy, 67846
- Central Care Cancer Center - Garden City
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Great Bend, Kansas, Spojené státy, 67530
- Central Care Cancer Center - Great Bend
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Kentucky
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Bardstown, Kentucky, Spojené státy, 40004
- Flaget Memorial Hospital
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Corbin, Kentucky, Spojené státy, 40701
- Commonwealth Cancer Center-Corbin
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Lexington, Kentucky, Spojené státy, 40504
- Saint Joseph Radiation Oncology Resource Center
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Lexington, Kentucky, Spojené státy, 40509
- Saint Joseph Hospital East
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London, Kentucky, Spojené státy, 40741
- Saint Joseph London
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Louisville, Kentucky, Spojené státy, 40202
- Jewish Hospital
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Louisville, Kentucky, Spojené státy, 40245
- UofL Health Medical Center Northeast
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Louisville, Kentucky, Spojené státy, 40215
- Saints Mary and Elizabeth Hospital
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Shepherdsville, Kentucky, Spojené státy, 40165
- Jewish Hospital Medical Center South
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Maryland
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Baltimore, Maryland, Spojené státy, 21237
- MedStar Franklin Square Medical Center/Weinberg Cancer Institute
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Minnesota
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Rochester, Minnesota, Spojené státy, 55905
- Mayo Clinic in Rochester
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Missouri
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Ballwin, Missouri, Spojené státy, 63011
- Saint Louis Cancer and Breast Institute-Ballwin
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Bolivar, Missouri, Spojené státy, 65613
- Central Care Cancer Center - Bolivar
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Branson, Missouri, Spojené státy, 65616
- Cox Cancer Center Branson
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Joplin, Missouri, Spojené státy, 64804
- Freeman Health System
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Joplin, Missouri, Spojené státy, 64804
- Mercy Hospital Joplin
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Rolla, Missouri, Spojené státy, 65401
- Delbert Day Cancer Institute at PCRMC
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Rolla, Missouri, Spojené státy, 65401
- Mercy Clinic-Rolla-Cancer and Hematology
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Saint Joseph, Missouri, Spojené státy, 64506
- Heartland Regional Medical Center
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Springfield, Missouri, Spojené státy, 65807
- CoxHealth South Hospital
-
Springfield, Missouri, Spojené státy, 65804
- Mercy Hospital Springfield
-
St Louis, Missouri, Spojené státy, 63141
- Mercy Hospital Saint Louis
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St Louis, Missouri, Spojené státy, 63128
- Mercy Hospital South
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St Louis, Missouri, Spojené státy, 63109
- Saint Louis Cancer and Breast Institute-South City
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Washington, Missouri, Spojené státy, 63090
- Mercy Hospital Washington
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Montana
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Missoula, Montana, Spojené státy, 59802
- Saint Patrick Hospital - Community Hospital
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Nebraska
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Grand Island, Nebraska, Spojené státy, 68803
- CHI Health Saint Francis
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Kearney, Nebraska, Spojené státy, 68847
- CHI Health Good Samaritan
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Lincoln, Nebraska, Spojené státy, 68510
- Saint Elizabeth Regional Medical Center
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Omaha, Nebraska, Spojené státy, 68124
- Alegent Health Bergan Mercy Medical Center
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Omaha, Nebraska, Spojené státy, 68122
- Alegent Health Immanuel Medical Center
-
Omaha, Nebraska, Spojené státy, 68130
- Alegent Health Lakeside Hospital
-
Omaha, Nebraska, Spojené státy, 68131
- Creighton University Medical Center
-
Papillion, Nebraska, Spojené státy, 68046
- Midlands Community Hospital
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New York
-
New York, New York, Spojené státy, 10016
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
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Ohio
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Beavercreek, Ohio, Spojené státy, 45431
- Indu and Raj Soin Medical Center
-
Boardman, Ohio, Spojené státy, 44512
- Saint Elizabeth Boardman Hospital
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Centerville, Ohio, Spojené státy, 45459
- Miami Valley Hospital South
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Centerville, Ohio, Spojené státy, 45459
- Dayton Physicians LLC-Miami Valley South
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Cincinnati, Ohio, Spojené státy, 45220
- Good Samaritan Hospital - Cincinnati
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Cincinnati, Ohio, Spojené státy, 45242
- Bethesda North Hospital
-
Cincinnati, Ohio, Spojené státy, 45236
- Oncology Hematology Care Inc-Kenwood
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Cincinnati, Ohio, Spojené státy, 45247
- TriHealth Cancer Institute-Westside
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Cincinnati, Ohio, Spojené státy, 45255
- TriHealth Cancer Institute-Anderson
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Dayton, Ohio, Spojené státy, 45409
- Miami Valley Hospital
-
Dayton, Ohio, Spojené státy, 45415
- Dayton Physician LLC-Miami Valley Hospital North
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Dayton, Ohio, Spojené státy, 45415
- Miami Valley Hospital North
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Findlay, Ohio, Spojené státy, 45840
- Blanchard Valley Hospital
-
Findlay, Ohio, Spojené státy, 45840
- Armes Family Cancer Center
-
Findlay, Ohio, Spojené státy, 45840
- Orion Cancer Care
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Franklin, Ohio, Spojené státy, 45005-1066
- Atrium Medical Center-Middletown Regional Hospital
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Franklin, Ohio, Spojené státy, 45005
- Dayton Physicians LLC-Atrium
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Greenville, Ohio, Spojené státy, 45331
- Wayne Hospital
-
Greenville, Ohio, Spojené státy, 45331
- Dayton Physicians LLC-Wayne
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Kettering, Ohio, Spojené státy, 45429
- Kettering Medical Center
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Kettering, Ohio, Spojené státy, 45409
- Greater Dayton Cancer Center
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Springfield, Ohio, Spojené státy, 45505
- Springfield Regional Medical Center
-
Springfield, Ohio, Spojené státy, 45504
- Springfield Regional Cancer Center
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Troy, Ohio, Spojené státy, 45373
- Upper Valley Medical Center
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Troy, Ohio, Spojené státy, 45373
- Dayton Physicians LLC-Upper Valley
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Warren, Ohio, Spojené státy, 44484
- Saint Joseph Warren Hospital
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Youngstown, Ohio, Spojené státy, 44501
- Saint Elizabeth Youngstown Hospital
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Oklahoma
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Oklahoma City, Oklahoma, Spojené státy, 73120
- Mercy Hospital Oklahoma City
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Oregon
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Bend, Oregon, Spojené státy, 97701
- Saint Charles Health System
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Clackamas, Oregon, Spojené státy, 97015
- Clackamas Radiation Oncology Center
-
Clackamas, Oregon, Spojené státy, 97015
- Providence Cancer Institute Clackamas Clinic
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Coos Bay, Oregon, Spojené státy, 97420
- Bay Area Hospital
-
Newberg, Oregon, Spojené státy, 97132
- Providence Newberg Medical Center
-
Portland, Oregon, Spojené státy, 97213
- Providence Portland Medical Center
-
Portland, Oregon, Spojené státy, 97225
- Providence Saint Vincent Medical Center
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Redmond, Oregon, Spojené státy, 97756
- Saint Charles Health System-Redmond
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Pennsylvania
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Chadds Ford, Pennsylvania, Spojené státy, 19317
- Christiana Care Health System-Concord Health Center
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Philadelphia, Pennsylvania, Spojené státy, 19104
- University of Pennsylvania/Abramson Cancer Center
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Pittsburgh, Pennsylvania, Spojené státy, 15232
- University of Pittsburgh Cancer Institute (UPCI)
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Texas
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Bryan, Texas, Spojené státy, 77802
- Saint Joseph Regional Cancer Center
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Utah
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Salt Lake City, Utah, Spojené státy, 84112
- Huntsman Cancer Institute/University of Utah
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Washington
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Aberdeen, Washington, Spojené státy, 98520
- Providence Regional Cancer System-Aberdeen
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Bellingham, Washington, Spojené státy, 98225
- PeaceHealth Saint Joseph Medical Center
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Bremerton, Washington, Spojené státy, 98310
- Harrison HealthPartners Hematology and Oncology-Bremerton
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Bremerton, Washington, Spojené státy, 98310
- Harrison Medical Center
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Burien, Washington, Spojené státy, 98166
- Highline Medical Center-Main Campus
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Centralia, Washington, Spojené státy, 98531
- Providence Regional Cancer System-Centralia
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Edmonds, Washington, Spojené státy, 98026
- Swedish Cancer Institute-Edmonds
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Enumclaw, Washington, Spojené státy, 98022
- Saint Elizabeth Hospital
-
Everett, Washington, Spojené státy, 98201
- Providence Regional Cancer Partnership
-
Federal Way, Washington, Spojené státy, 98003
- Saint Francis Hospital
-
Issaquah, Washington, Spojené státy, 98029
- Swedish Cancer Institute-Issaquah
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Kennewick, Washington, Spojené státy, 99336
- Kadlec Clinic Hematology and Oncology
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Lacey, Washington, Spojené státy, 98503
- Providence Regional Cancer System-Lacey
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Lakewood, Washington, Spojené státy, 98499
- Saint Clare Hospital
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Longview, Washington, Spojené státy, 98632
- PeaceHealth Saint John Medical Center
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Poulsbo, Washington, Spojené státy, 98370
- Harrison HealthPartners Hematology and Oncology-Poulsbo
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Seattle, Washington, Spojené státy, 98107
- Swedish Medical Center-Ballard Campus
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Seattle, Washington, Spojené státy, 98122
- Swedish Medical Center-First Hill
-
Seattle, Washington, Spojené státy, 98104
- Pacific Gynecology Specialists
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Seattle, Washington, Spojené státy, 98122-5711
- Swedish Medical Center-Cherry Hill
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Sedro-Woolley, Washington, Spojené státy, 98284
- PeaceHealth United General Medical Center
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Shelton, Washington, Spojené státy, 98584
- Providence Regional Cancer System-Shelton
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Tacoma, Washington, Spojené státy, 98405
- Franciscan Research Center-Northwest Medical Plaza
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Vancouver, Washington, Spojené státy, 98664
- PeaceHealth Southwest Medical Center
-
Walla Walla, Washington, Spojené státy, 99362
- Providence Saint Mary Regional Cancer Center
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Yelm, Washington, Spojené státy, 98597
- Providence Regional Cancer System-Yelm
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Wisconsin
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Chippewa Falls, Wisconsin, Spojené státy, 54729
- Marshfield Clinic-Chippewa Center
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Eau Claire, Wisconsin, Spojené státy, 54701
- Marshfield Medical Center-EC Cancer Center
-
Ladysmith, Wisconsin, Spojené státy, 54848
- Marshfield Clinic - Ladysmith Center
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Marshfield, Wisconsin, Spojené státy, 54449
- Marshfield Medical Center-Marshfield
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Minocqua, Wisconsin, Spojené státy, 54548
- Marshfield Clinic-Minocqua Center
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Rice Lake, Wisconsin, Spojené státy, 54868
- Marshfield Medical Center-Rice Lake
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Stevens Point, Wisconsin, Spojené státy, 54482
- Marshfield Medical Center-River Region at Stevens Point
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Wausau, Wisconsin, Spojené státy, 54401
- Marshfield Clinic-Wausau Center
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Weston, Wisconsin, Spojené státy, 54476
- Marshfield Medical Center - Weston
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Wisconsin Rapids, Wisconsin, Spojené státy, 54494
- Marshfield Clinic - Wisconsin Rapids Center
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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
-
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
-
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)
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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)
-
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
-
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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Dvojnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: 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
Ostatní jména:
Given PO
Ostatní jména:
Given PO
Ostatní jména:
|
|
Aktivní komparátor: 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
Ostatní jména:
Given PO
Ostatní jména:
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
One-year Progression-free Survival Rate
Časové okno: 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
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Progression-free Survival
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
|
Spolupracovníci a vyšetřovatelé
Sponzor
Spolupracovníci
Vyšetřovatelé
- Vrchní vyšetřovatel: Ravi Amaravadi, ECOG-ACRIN Cancer Research Group
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
- EA6191
- U10CA180820 (Grant/smlouva NIH USA)
- EA6191 (Jiný identifikátor: CTEP)
- NCI-2020-04552 (Identifikátor registru: CTRP (Clinical Trial Reporting Program))
- EA6191 (Jiný identifikátor: ECOG-ACRIN Cancer Research Group)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu IPD
Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
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