Test af Dabrafenib og Trametinib med eller uden hydroxychloroquin i trin IIIC eller IV BRAF V600E/K melanom
BAMM2 (BRAF, Autophagy, MEK Inhibition in Melanoma) Studiet: Et randomiseret dobbeltblindt fase II-studie af Dabrafenib og Trametinib med eller uden hydroxychloroquin i avanceret BRAF V600E/K melanom
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.
Studieoversigt
Status
Betingelser
Detaljeret beskrivelse
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.
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
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Alaska
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Anchorage, Alaska, Forenede Stater, 98508
- Anchorage Associates in Radiation Medicine
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Anchorage, Alaska, Forenede Stater, 99508
- Alaska Breast Care and Surgery LLC
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Anchorage, Alaska, Forenede Stater, 99508
- Alaska Oncology and Hematology LLC
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Anchorage, Alaska, Forenede Stater, 99508
- Alaska Women's Cancer Care
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Anchorage, Alaska, Forenede Stater, 99508
- Anchorage Oncology Centre
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Anchorage, Alaska, Forenede Stater, 99508
- Katmai Oncology Group
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Anchorage, Alaska, Forenede Stater, 99508
- Providence Alaska Medical Center
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Anchorage, Alaska, Forenede Stater, 99504
- Anchorage Radiation Therapy Center
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Arizona
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Phoenix, Arizona, Forenede Stater, 85054
- Mayo Clinic Hospital in Arizona
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Phoenix, Arizona, Forenede Stater, 85004
- Cancer Center at Saint Joseph's
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Scottsdale, Arizona, Forenede Stater, 85259
- Mayo Clinic in Arizona
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Arkansas
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Fort Smith, Arkansas, Forenede Stater, 72903
- Mercy Hospital Fort Smith
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Hot Springs, Arkansas, Forenede Stater, 71913
- CHI Saint Vincent Cancer Center Hot Springs
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California
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Arroyo Grande, California, Forenede Stater, 93420
- Mission Hope Medical Oncology - Arroyo Grande
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Burbank, California, Forenede Stater, 91505
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
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Los Angeles, California, Forenede Stater, 90048
- Cedars Sinai Medical Center
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San Luis Obispo, California, Forenede Stater, 93401
- Pacific Central Coast Health Center-San Luis Obispo
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Santa Maria, California, Forenede Stater, 93444
- Mission Hope Medical Oncology - Santa Maria
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Colorado
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Colorado Springs, Colorado, Forenede Stater, 80907
- Penrose-Saint Francis Healthcare
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Colorado Springs, Colorado, Forenede Stater, 80907
- Rocky Mountain Cancer Centers-Penrose
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Colorado Springs, Colorado, Forenede Stater, 80923
- Saint Francis Cancer Center
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Denver, Colorado, Forenede Stater, 80210
- Porter Adventist Hospital
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Durango, Colorado, Forenede Stater, 81301
- Mercy Medical Center
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Durango, Colorado, Forenede Stater, 81301
- Southwest Oncology PC
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Lakewood, Colorado, Forenede Stater, 80228
- Saint Anthony Hospital
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Littleton, Colorado, Forenede Stater, 80122
- Littleton Adventist Hospital
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Longmont, Colorado, Forenede Stater, 80501
- Longmont United Hospital
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Longmont, Colorado, Forenede Stater, 80501
- Rocky Mountain Cancer Centers-Longmont
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Parker, Colorado, Forenede Stater, 80138
- Parker Adventist Hospital
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Pueblo, Colorado, Forenede Stater, 81004
- Saint Mary Corwin Medical Center
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Delaware
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Frankford, Delaware, Forenede Stater, 19945
- Beebe South Coastal Health Campus
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Lewes, Delaware, Forenede Stater, 19958
- Beebe Medical Center
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Newark, Delaware, Forenede Stater, 19713
- Helen F Graham Cancer Center
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Newark, Delaware, Forenede Stater, 19713
- Delaware Clinical and Laboratory Physicians PA
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Newark, Delaware, Forenede Stater, 19713
- Medical Oncology Hematology Consultants PA
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Newark, Delaware, Forenede Stater, 19718
- Christiana Care Health System-Christiana Hospital
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Rehoboth Beach, Delaware, Forenede Stater, 19971
- Beebe Health Campus
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Seaford, Delaware, Forenede Stater, 19973
- TidalHealth Nanticoke / Allen Cancer Center
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Wilmington, Delaware, Forenede Stater, 19801
- Christiana Care Health System-Wilmington Hospital
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District of Columbia
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Washington D.C., District of Columbia, Forenede Stater, 20007
- MedStar Georgetown University Hospital
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Florida
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Aventura, Florida, Forenede Stater, 33180
- UM Sylvester Comprehensive Cancer Center at Aventura
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Coral Gables, Florida, Forenede Stater, 33146
- UM Sylvester Comprehensive Cancer Center at Coral Gables
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Deerfield Beach, Florida, Forenede Stater, 33442
- UM Sylvester Comprehensive Cancer Center at Deerfield Beach
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Miami, Florida, Forenede Stater, 33136
- University of Miami Miller School of Medicine-Sylvester Cancer Center
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Miami, Florida, Forenede Stater, 33176
- UM Sylvester Comprehensive Cancer Center at Kendall
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Plantation, Florida, Forenede Stater, 33324
- UM Sylvester Comprehensive Cancer Center at Plantation
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Idaho
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Boise, Idaho, Forenede Stater, 83712
- Saint Luke's Cancer Institute - Boise
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Fruitland, Idaho, Forenede Stater, 83619
- Saint Luke's Cancer Institute - Fruitland
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Meridian, Idaho, Forenede Stater, 83642
- Saint Luke's Cancer Institute - Meridian
-
Nampa, Idaho, Forenede Stater, 83686
- Saint Luke's Cancer Institute - Nampa
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Twin Falls, Idaho, Forenede Stater, 83301
- Saint Luke's Cancer Institute - Twin Falls
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Illinois
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Alton, Illinois, Forenede Stater, 62002
- Saint Anthony's Health
-
Aurora, Illinois, Forenede Stater, 60504
- Rush - Copley Medical Center
-
Burr Ridge, Illinois, Forenede Stater, 60527
- Loyola Center for Health at Burr Ridge
-
Danville, Illinois, Forenede Stater, 61832
- Carle on Vermilion
-
Effingham, Illinois, Forenede Stater, 62401
- Carle Physician Group-Effingham
-
Homer Glen, Illinois, Forenede Stater, 60491
- Loyola Medicine Homer Glen
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Mattoon, Illinois, Forenede Stater, 61938
- Carle Physician Group-Mattoon/Charleston
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Maywood, Illinois, Forenede Stater, 60153
- Loyola University Medical Center
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Melrose Park, Illinois, Forenede Stater, 60160
- Marjorie Weinberg Cancer Center at Loyola-Gottlieb
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Mount Vernon, Illinois, Forenede Stater, 62864
- Good Samaritan Regional Health Center
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Urbana, Illinois, Forenede Stater, 61801
- Carle Cancer Center
-
Urbana, Illinois, Forenede Stater, 61801
- The Carle Foundation Hospital
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Yorkville, Illinois, Forenede Stater, 60560
- Rush-Copley Healthcare Center
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Indiana
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Richmond, Indiana, Forenede Stater, 47374
- Reid Health
-
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Iowa
-
Ames, Iowa, Forenede Stater, 50010
- McFarland Clinic PC - Ames
-
Ames, Iowa, Forenede Stater, 50010
- Mary Greeley Medical Center
-
Boone, Iowa, Forenede Stater, 50036
- McFarland Clinic PC-Boone
-
Carroll, Iowa, Forenede Stater, 51401
- Saint Anthony Regional Hospital
-
Clive, Iowa, Forenede Stater, 50325
- Mercy Cancer Center-West Lakes
-
Clive, Iowa, Forenede Stater, 50325
- Medical Oncology and Hematology Associates-West Des Moines
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Council Bluffs, Iowa, Forenede Stater, 51503
- Alegent Health Mercy Hospital
-
Creston, Iowa, Forenede Stater, 50801
- Greater Regional Medical Center
-
Des Moines, Iowa, Forenede Stater, 50309
- Iowa Methodist Medical Center
-
Des Moines, Iowa, Forenede Stater, 50314
- Mercy Medical Center - Des Moines
-
Des Moines, Iowa, Forenede Stater, 50309
- Medical Oncology and Hematology Associates-Des Moines
-
Des Moines, Iowa, Forenede Stater, 50314
- Broadlawns Medical Center
-
Des Moines, Iowa, Forenede Stater, 50314
- Mission Cancer and Blood - Laurel
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Des Moines, Iowa, Forenede Stater, 50316
- Iowa Lutheran Hospital
-
Fort Dodge, Iowa, Forenede Stater, 50501
- McFarland Clinic PC-Trinity Cancer Center
-
Fort Dodge, Iowa, Forenede Stater, 50501
- Trinity Regional Medical Center
-
Jefferson, Iowa, Forenede Stater, 50129
- McFarland Clinic PC-Jefferson
-
Marshalltown, Iowa, Forenede Stater, 50158
- McFarland Clinic PC-Marshalltown
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West Des Moines, Iowa, Forenede Stater, 50266-7700
- Methodist West Hospital
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West Des Moines, Iowa, Forenede Stater, 50266
- Mercy Medical Center-West Lakes
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Kansas
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Garden City, Kansas, Forenede Stater, 67846
- Central Care Cancer Center - Garden City
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Great Bend, Kansas, Forenede Stater, 67530
- Central Care Cancer Center - Great Bend
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Kentucky
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Bardstown, Kentucky, Forenede Stater, 40004
- Flaget Memorial Hospital
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Corbin, Kentucky, Forenede Stater, 40701
- Commonwealth Cancer Center-Corbin
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Lexington, Kentucky, Forenede Stater, 40504
- Saint Joseph Radiation Oncology Resource Center
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Lexington, Kentucky, Forenede Stater, 40509
- Saint Joseph Hospital East
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London, Kentucky, Forenede Stater, 40741
- Saint Joseph London
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Louisville, Kentucky, Forenede Stater, 40202
- Jewish Hospital
-
Louisville, Kentucky, Forenede Stater, 40245
- UofL Health Medical Center Northeast
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Louisville, Kentucky, Forenede Stater, 40215
- Saints Mary and Elizabeth Hospital
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Shepherdsville, Kentucky, Forenede Stater, 40165
- Jewish Hospital Medical Center South
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Maryland
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Baltimore, Maryland, Forenede Stater, 21237
- MedStar Franklin Square Medical Center/Weinberg Cancer Institute
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Minnesota
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Rochester, Minnesota, Forenede Stater, 55905
- Mayo Clinic in Rochester
-
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Missouri
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Ballwin, Missouri, Forenede Stater, 63011
- Saint Louis Cancer and Breast Institute-Ballwin
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Bolivar, Missouri, Forenede Stater, 65613
- Central Care Cancer Center - Bolivar
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Branson, Missouri, Forenede Stater, 65616
- Cox Cancer Center Branson
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Joplin, Missouri, Forenede Stater, 64804
- Freeman Health System
-
Joplin, Missouri, Forenede Stater, 64804
- Mercy Hospital Joplin
-
Rolla, Missouri, Forenede Stater, 65401
- Delbert Day Cancer Institute at PCRMC
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Rolla, Missouri, Forenede Stater, 65401
- Mercy Clinic-Rolla-Cancer and Hematology
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Saint Joseph, Missouri, Forenede Stater, 64506
- Heartland Regional Medical Center
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Springfield, Missouri, Forenede Stater, 65807
- CoxHealth South Hospital
-
Springfield, Missouri, Forenede Stater, 65804
- Mercy Hospital Springfield
-
St Louis, Missouri, Forenede Stater, 63141
- Mercy Hospital Saint Louis
-
St Louis, Missouri, Forenede Stater, 63128
- Mercy Hospital South
-
St Louis, Missouri, Forenede Stater, 63109
- Saint Louis Cancer and Breast Institute-South City
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Washington, Missouri, Forenede Stater, 63090
- Mercy Hospital Washington
-
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Montana
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Missoula, Montana, Forenede Stater, 59802
- Saint Patrick Hospital - Community Hospital
-
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Nebraska
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Grand Island, Nebraska, Forenede Stater, 68803
- CHI Health Saint Francis
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Kearney, Nebraska, Forenede Stater, 68847
- CHI Health Good Samaritan
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Lincoln, Nebraska, Forenede Stater, 68510
- Saint Elizabeth Regional Medical Center
-
Omaha, Nebraska, Forenede Stater, 68124
- Alegent Health Bergan Mercy Medical Center
-
Omaha, Nebraska, Forenede Stater, 68122
- Alegent Health Immanuel Medical Center
-
Omaha, Nebraska, Forenede Stater, 68130
- Alegent Health Lakeside Hospital
-
Omaha, Nebraska, Forenede Stater, 68131
- Creighton University Medical Center
-
Papillion, Nebraska, Forenede Stater, 68046
- Midlands Community Hospital
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New York
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New York, New York, Forenede Stater, 10016
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
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Ohio
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Beavercreek, Ohio, Forenede Stater, 45431
- Indu and Raj Soin Medical Center
-
Boardman, Ohio, Forenede Stater, 44512
- Saint Elizabeth Boardman Hospital
-
Centerville, Ohio, Forenede Stater, 45459
- Miami Valley Hospital South
-
Centerville, Ohio, Forenede Stater, 45459
- Dayton Physicians LLC-Miami Valley South
-
Cincinnati, Ohio, Forenede Stater, 45220
- Good Samaritan Hospital - Cincinnati
-
Cincinnati, Ohio, Forenede Stater, 45242
- Bethesda North Hospital
-
Cincinnati, Ohio, Forenede Stater, 45236
- Oncology Hematology Care Inc-Kenwood
-
Cincinnati, Ohio, Forenede Stater, 45247
- TriHealth Cancer Institute-Westside
-
Cincinnati, Ohio, Forenede Stater, 45255
- TriHealth Cancer Institute-Anderson
-
Dayton, Ohio, Forenede Stater, 45409
- Miami Valley Hospital
-
Dayton, Ohio, Forenede Stater, 45415
- Dayton Physician LLC-Miami Valley Hospital North
-
Dayton, Ohio, Forenede Stater, 45415
- Miami Valley Hospital North
-
Findlay, Ohio, Forenede Stater, 45840
- Blanchard Valley Hospital
-
Findlay, Ohio, Forenede Stater, 45840
- Armes Family Cancer Center
-
Findlay, Ohio, Forenede Stater, 45840
- Orion Cancer Care
-
Franklin, Ohio, Forenede Stater, 45005-1066
- Atrium Medical Center-Middletown Regional Hospital
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Franklin, Ohio, Forenede Stater, 45005
- Dayton Physicians LLC-Atrium
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Greenville, Ohio, Forenede Stater, 45331
- Wayne Hospital
-
Greenville, Ohio, Forenede Stater, 45331
- Dayton Physicians LLC-Wayne
-
Kettering, Ohio, Forenede Stater, 45429
- Kettering Medical Center
-
Kettering, Ohio, Forenede Stater, 45409
- Greater Dayton Cancer Center
-
Springfield, Ohio, Forenede Stater, 45505
- Springfield Regional Medical Center
-
Springfield, Ohio, Forenede Stater, 45504
- Springfield Regional Cancer Center
-
Troy, Ohio, Forenede Stater, 45373
- Upper Valley Medical Center
-
Troy, Ohio, Forenede Stater, 45373
- Dayton Physicians LLC-Upper Valley
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Warren, Ohio, Forenede Stater, 44484
- Saint Joseph Warren Hospital
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Youngstown, Ohio, Forenede Stater, 44501
- Saint Elizabeth Youngstown Hospital
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Oklahoma
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Oklahoma City, Oklahoma, Forenede Stater, 73120
- Mercy Hospital Oklahoma City
-
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Oregon
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Bend, Oregon, Forenede Stater, 97701
- Saint Charles Health System
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Clackamas, Oregon, Forenede Stater, 97015
- Clackamas Radiation Oncology Center
-
Clackamas, Oregon, Forenede Stater, 97015
- Providence Cancer Institute Clackamas Clinic
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Coos Bay, Oregon, Forenede Stater, 97420
- Bay Area Hospital
-
Newberg, Oregon, Forenede Stater, 97132
- Providence Newberg Medical Center
-
Portland, Oregon, Forenede Stater, 97213
- Providence Portland Medical Center
-
Portland, Oregon, Forenede Stater, 97225
- Providence Saint Vincent Medical Center
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Redmond, Oregon, Forenede Stater, 97756
- Saint Charles Health System-Redmond
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Pennsylvania
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Chadds Ford, Pennsylvania, Forenede Stater, 19317
- Christiana Care Health System-Concord Health Center
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Philadelphia, Pennsylvania, Forenede Stater, 19104
- University of Pennsylvania/Abramson Cancer Center
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Pittsburgh, Pennsylvania, Forenede Stater, 15232
- University of Pittsburgh Cancer Institute (UPCI)
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Texas
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Bryan, Texas, Forenede Stater, 77802
- Saint Joseph Regional Cancer Center
-
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Utah
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Salt Lake City, Utah, Forenede Stater, 84112
- Huntsman Cancer Institute/University of Utah
-
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Washington
-
Aberdeen, Washington, Forenede Stater, 98520
- Providence Regional Cancer System-Aberdeen
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Bellingham, Washington, Forenede Stater, 98225
- PeaceHealth Saint Joseph Medical Center
-
Bremerton, Washington, Forenede Stater, 98310
- Harrison HealthPartners Hematology and Oncology-Bremerton
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Bremerton, Washington, Forenede Stater, 98310
- Harrison Medical Center
-
Burien, Washington, Forenede Stater, 98166
- Highline Medical Center-Main Campus
-
Centralia, Washington, Forenede Stater, 98531
- Providence Regional Cancer System-Centralia
-
Edmonds, Washington, Forenede Stater, 98026
- Swedish Cancer Institute-Edmonds
-
Enumclaw, Washington, Forenede Stater, 98022
- Saint Elizabeth Hospital
-
Everett, Washington, Forenede Stater, 98201
- Providence Regional Cancer Partnership
-
Federal Way, Washington, Forenede Stater, 98003
- Saint Francis Hospital
-
Issaquah, Washington, Forenede Stater, 98029
- Swedish Cancer Institute-Issaquah
-
Kennewick, Washington, Forenede Stater, 99336
- Kadlec Clinic Hematology and Oncology
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Lacey, Washington, Forenede Stater, 98503
- Providence Regional Cancer System-Lacey
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Lakewood, Washington, Forenede Stater, 98499
- Saint Clare Hospital
-
Longview, Washington, Forenede Stater, 98632
- PeaceHealth Saint John Medical Center
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Poulsbo, Washington, Forenede Stater, 98370
- Harrison HealthPartners Hematology and Oncology-Poulsbo
-
Seattle, Washington, Forenede Stater, 98107
- Swedish Medical Center-Ballard Campus
-
Seattle, Washington, Forenede Stater, 98122
- Swedish Medical Center-First Hill
-
Seattle, Washington, Forenede Stater, 98104
- Pacific Gynecology Specialists
-
Seattle, Washington, Forenede Stater, 98122-5711
- Swedish Medical Center-Cherry Hill
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Sedro-Woolley, Washington, Forenede Stater, 98284
- PeaceHealth United General Medical Center
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Shelton, Washington, Forenede Stater, 98584
- Providence Regional Cancer System-Shelton
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Tacoma, Washington, Forenede Stater, 98405
- Franciscan Research Center-Northwest Medical Plaza
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Vancouver, Washington, Forenede Stater, 98664
- PeaceHealth Southwest Medical Center
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Walla Walla, Washington, Forenede Stater, 99362
- Providence Saint Mary Regional Cancer Center
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Yelm, Washington, Forenede Stater, 98597
- Providence Regional Cancer System-Yelm
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Wisconsin
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Chippewa Falls, Wisconsin, Forenede Stater, 54729
- Marshfield Clinic-Chippewa Center
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Eau Claire, Wisconsin, Forenede Stater, 54701
- Marshfield Medical Center-EC Cancer Center
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Ladysmith, Wisconsin, Forenede Stater, 54848
- Marshfield Clinic - Ladysmith Center
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Marshfield, Wisconsin, Forenede Stater, 54449
- Marshfield Medical Center-Marshfield
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Minocqua, Wisconsin, Forenede Stater, 54548
- Marshfield Clinic-Minocqua Center
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Rice Lake, Wisconsin, Forenede Stater, 54868
- Marshfield Medical Center-Rice Lake
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Stevens Point, Wisconsin, Forenede Stater, 54482
- Marshfield Medical Center-River Region at Stevens Point
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Wausau, Wisconsin, Forenede Stater, 54401
- Marshfield Clinic-Wausau Center
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Weston, Wisconsin, Forenede Stater, 54476
- Marshfield Medical Center - Weston
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Wisconsin Rapids, Wisconsin, Forenede Stater, 54494
- Marshfield Clinic - Wisconsin Rapids Center
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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
-
Patient may have been treated with prior adjuvant therapy including combined BRAF and MEK inhibitor therapy. Patients will be eligible if they tolerated this therapy and did not discontinue the therapy due to toxicity AND >= 6 months have elapsed since the end of adjuvant BRAF and MEK inhibition.
-
Patient may have been treated with prior chemotherapy or radiation therapy
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Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
-
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
-
All females of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy.
-
Women of childbearing potential and sexually active males must not expect to conceive or father children by using accepted and effective method(s) of contraception or abstaining from sexual intercourse for the duration of their participation in the study and for 4 months after the last dose of protocol treatment
-
Patient must have recovered from clinically significant reversible toxicities from previous treatment prior to randomization. Abnormal laboratory values may be grade 1, as long as they meet the eligibility criteria for organ and marrow function
-
Patient must be able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
-
Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
-
Absolute neutrophil count >= 1,500/mcL (obtained =< 14 days prior to protocol randomization)
-
Platelets >= 100,000/mcL (obtained =< 14 days prior to protocol randomization)
-
Total bilirubin =< institutional upper limit of normal (ULN) (obtained =< 14 days prior to protocol randomization)
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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
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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)
-
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)
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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
-
Current use of a prohibited medication described in the protocol due to potential drug-drug interaction
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Dobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: 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
Andre navne:
Given PO
Andre navne:
Given PO
Andre navne:
|
|
Aktiv komparator: 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
Andre navne:
Given PO
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
One-year Progression-free Survival Rate
Tidsramme: 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
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Progression-free Survival
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
|
Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Ravi Amaravadi, ECOG-ACRIN Cancer Research Group
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- EA6191
- U10CA180820 (U.S. NIH-bevilling/kontrakt)
- EA6191 (Anden identifikator: CTEP)
- NCI-2020-04552 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- EA6191 (Anden identifikator: ECOG-ACRIN Cancer Research Group)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Studerer et amerikansk FDA-reguleret enhedsprodukt
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