Vemurafenib and Cobimetinib in Treating Patients with BRAF V600E Mutation Positive Craniopharyngioma
- Conditions
- BRAF V600E Mutation PresentPapillary Craniopharyngioma
- Interventions
- Other: Laboratory Biomarker AnalysisOther: Quality-of-Life Assessment
- Registration Number
- NCT03224767
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
This phase II trial studies how well vemurafenib and cobimetinib work in treating patients with BRAF V600E mutation positive craniopharyngioma. Vemurafenib and cobimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
- Detailed Description
PRIMARY OBJECTIVES:
I. To determine the activity of BRAF and MEK inhibitor combination in untreated papillary craniopharyngiomas as measured by best response at any time during the first four cycles of BRAF and MEK inhibitor treatment.
II. To determine the activity of BRAF and MEK inhibitor combination in papillary craniopharyngiomas that have progressed after prior radiation treatment with or without surgical resection as measured by best response at any time during the first four cycles of BRAF and MEK inhibitor treatment.
SECONDARY OBJECTIVES:
I. To determine the progression-free survival of patients with papillary craniopharyngiomas receiving BRAF and MEK inhibitors.
II. To determine the toxicity of BRAF/MEK inhibitors in patients with papillary craniopharyngiomas.
III. To determine the activity of BRAF and MEK inhibitor combination in papillary craniopharyngiomas as measured by response of enhancing volume of craniopharyngioma.
IV. To determine the activity of BRAF and MEK inhibitor combination in papillary craniopharyngiomas as measured by response of nonenhancing volume of craniopharyngioma.
V. To determine the overall survival of patients with papillary craniopharyngiomas receiving BRAF and MEK inhibitors.
VI. To determine the duration of response in patients with papillary craniopharyngiomas receiving BRAF and MEK inhibitors.
TERTIARY OBJECTIVES:
I. To evaluate visual fields in patients with papillary craniopharyngiomas who have received BRAF/MEK inhibitors.
II. To evaluate pituitary hormone replacement over time in patients with papillary craniopharyngiomas who have received BRAF/MEK inhibitors.
III. To evaluate the time to response in patients with papillary craniopharyngiomas receiving BRAF and MEK inhibitors.
IV. To assess toxicity that may be associated with radiotherapy in patients with papillary craniopharyngiomas who have received BRAF/MEK inhibitors.
V. To evaluate molecular biomarkers of response in papillary craniopharyngiomas.
VI. To evaluate circulating tumor cells and cell-free circulating deoxyribonucleic acid (DNA) in patients with papillary craniopharyngiomas.
OUTLINE:
Patients receive vemurafenib orally (PO) twice daily (BID) on day 1-28 and cobimetinib PO once daily (QD) on days 1-21. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients may then receive radiation therapy, surgery, or continued treatment with vemurafenib and cobimetinib at the discretion of the treating physician.
After completion of study treatment, patients with disease progression are followed up every 16 weeks for 2 years and all other patients are followed up every 6 months for 5 years.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 24
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (vemurafenib, cobimetinib) Laboratory Biomarker Analysis Patients receive vemurafenib PO BID on day 1-28 and cobimetinib PO QD on days 1-21. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients may then receive radiation therapy, surgery, or continued treatment with vemurafenib and cobimetinib at the discretion of the treating physician. Treatment (vemurafenib, cobimetinib) Quality-of-Life Assessment Patients receive vemurafenib PO BID on day 1-28 and cobimetinib PO QD on days 1-21. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients may then receive radiation therapy, surgery, or continued treatment with vemurafenib and cobimetinib at the discretion of the treating physician. Treatment (vemurafenib, cobimetinib) Vemurafenib Patients receive vemurafenib PO BID on day 1-28 and cobimetinib PO QD on days 1-21. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients may then receive radiation therapy, surgery, or continued treatment with vemurafenib and cobimetinib at the discretion of the treating physician. Treatment (vemurafenib, cobimetinib) Cobimetinib Patients receive vemurafenib PO BID on day 1-28 and cobimetinib PO QD on days 1-21. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients may then receive radiation therapy, surgery, or continued treatment with vemurafenib and cobimetinib at the discretion of the treating physician.
- Primary Outcome Measures
Name Time Method Response rate Up to 5 years Defined as the number of responses achieved during treatment with BRAF and MEK inhibitors divided by the total number of evaluable patients and assessed by contrast-enhanced magnetic resonance imaging or computed tomography. Point estimates will be generated for response rates within each cohort with corresponding 95% binomial confidence intervals. Simon's two-stage design with one interim analysis for futility will be applied to evaluate response rate within each cohort.
- Secondary Outcome Measures
Name Time Method Progression-free survival Up to 5 years Will be summarized for each cohort within each cohort with Kaplan-Meier curves and estimates.
Overall survival Up to 5 years Will be summarized for each cohort within each cohort with Kaplan-Meier curves and estimates.
Trial Locations
- Locations (106)
Alta Bates Summit Medical Center-Herrick Campus
🇺🇸Berkeley, California, United States
Palo Alto Medical Foundation-Camino Division
🇺🇸Mountain View, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
Mills-Peninsula Medical Center
🇺🇸Burlingame, California, United States
Sutter Cancer Centers Radiation Oncology Services-Cameron Park
🇺🇸Cameron Park, California, United States
Eden Hospital Medical Center
🇺🇸Castro Valley, California, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
Memorial Medical Center
🇺🇸Modesto, California, United States
Palo Alto Medical Foundation Health Care
🇺🇸Palo Alto, California, United States
Sutter Cancer Centers Radiation Oncology Services-Roseville
🇺🇸Roseville, California, United States
Sutter Medical Center Sacramento
🇺🇸Sacramento, California, United States
Sutter Roseville Medical Center
🇺🇸Roseville, California, United States
California Pacific Medical Center-Pacific Campus
🇺🇸San Francisco, California, United States
Palo Alto Medical Foundation-Sunnyvale
🇺🇸Sunnyvale, California, United States
Sutter Cancer Centers Radiation Oncology Services-Vacaville
🇺🇸Vacaville, California, United States
Sutter Solano Medical Center/Cancer Center
🇺🇸Vallejo, California, United States
Smilow Cancer Center/Yale-New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Tampa General Hospital
🇺🇸Tampa, Florida, United States
Saint Alphonsus Cancer Care Center-Boise
🇺🇸Boise, Idaho, United States
Kootenai Clinic Cancer Services - Post Falls
🇺🇸Post Falls, Idaho, United States
Smilow Cancer Hospital Care Center-Trumbull
🇺🇸Trumbull, Connecticut, United States
Mayo Clinic in Florida
🇺🇸Jacksonville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Saint Alphonsus Cancer Care Center-Caldwell
🇺🇸Caldwell, Idaho, United States
Kootenai Health - Coeur d'Alene
🇺🇸Coeur D'Alene, Idaho, United States
Idaho Urologic Institute-Meridian
🇺🇸Meridian, Idaho, United States
Saint Alphonsus Cancer Care Center-Nampa
🇺🇸Nampa, Idaho, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Central Care Cancer Center - Garden City
🇺🇸Garden City, Kansas, United States
Central Care Cancer Center - Great Bend
🇺🇸Great Bend, Kansas, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
🇺🇸Grand Rapids, Michigan, United States
Trinity Health Grand Rapids Hospital
🇺🇸Grand Rapids, Michigan, United States
University of Michigan Health - West
🇺🇸Wyoming, Michigan, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Bronson Battle Creek
🇺🇸Battle Creek, Michigan, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
🇺🇸Grand Rapids, Michigan, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Borgess Medical Center
🇺🇸Kalamazoo, Michigan, United States
Trinity Health Muskegon Hospital
🇺🇸Muskegon, Michigan, United States
Corewell Health Lakeland Hospitals - Niles Hospital
🇺🇸Niles, Michigan, United States
Cancer and Hematology Centers of Western Michigan - Norton Shores
🇺🇸Norton Shores, Michigan, United States
Corewell Health Reed City Hospital
🇺🇸Reed City, Michigan, United States
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
🇺🇸Saint Joseph, Michigan, United States
Corewell Health Lakeland Hospitals - Saint Joseph Hospital
🇺🇸Saint Joseph, Michigan, United States
Munson Medical Center
🇺🇸Traverse City, Michigan, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
Minnesota Oncology - Burnsville
🇺🇸Burnsville, Minnesota, United States
Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Unity Hospital
🇺🇸Fridley, Minnesota, United States
Fairview Clinics and Surgery Center Maple Grove
🇺🇸Maple Grove, Minnesota, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸Maplewood, Minnesota, United States
Saint John's Hospital - Healtheast
🇺🇸Maplewood, Minnesota, United States
Monticello Cancer Center
🇺🇸Monticello, Minnesota, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
Rice Memorial Hospital
🇺🇸Willmar, Minnesota, United States
Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
Health Partners Inc
🇺🇸Minneapolis, Minnesota, United States
North Memorial Medical Health Center
🇺🇸Robbinsdale, Minnesota, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸Saint Louis Park, Minnesota, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Saint Francis Regional Medical Center
🇺🇸Shakopee, Minnesota, United States
Lakeview Hospital
🇺🇸Stillwater, Minnesota, United States
Central Care Cancer Center - Bolivar
🇺🇸Bolivar, Missouri, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
Minnesota Oncology Hematology PA-Woodbury
🇺🇸Woodbury, Minnesota, United States
Research Medical Center
🇺🇸Kansas City, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Billings Clinic Cancer Center
🇺🇸Billings, Montana, United States
Bozeman Health Deaconess Hospital
🇺🇸Bozeman, Montana, United States
Benefis Sletten Cancer Institute
🇺🇸Great Falls, Montana, United States
Great Falls Clinic
🇺🇸Great Falls, Montana, United States
Kalispell Regional Medical Center
🇺🇸Kalispell, Montana, United States
Community Medical Center
🇺🇸Missoula, Montana, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
🇺🇸Lebanon, New Hampshire, United States
Rutgers New Jersey Medical School
🇺🇸Newark, New Jersey, United States
NYP/Weill Cornell Medical Center
🇺🇸New York, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
🇺🇸New York, New York, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Cancer Centers of Southwest Oklahoma Research
🇺🇸Lawton, Oklahoma, United States
M D Anderson Cancer Center
🇺🇸Houston, Texas, United States
Huntsman Cancer Institute/University of Utah
🇺🇸Salt Lake City, Utah, United States
Inova Schar Cancer Institute
🇺🇸Fairfax, Virginia, United States
University of Washington Medical Center - Montlake
🇺🇸Seattle, Washington, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Farmington Health Center
🇺🇸Farmington, Utah, United States
South Jordan Health Center
🇺🇸South Jordan, Utah, United States
FHCC South Lake Union
🇺🇸Seattle, Washington, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
Aurora Saint Luke's Medical Center
🇺🇸Milwaukee, Wisconsin, United States
Welch Cancer Center
🇺🇸Sheridan, Wyoming, United States
United Hospital Center
🇺🇸Bridgeport, West Virginia, United States
West Virginia University Healthcare
🇺🇸Morgantown, West Virginia, United States
Cancer Center of Western Wisconsin
🇺🇸New Richmond, Wisconsin, United States
Camden Clark Medical Center
🇺🇸Parkersburg, West Virginia, United States
University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States
Sutter Cancer Centers Radiation Oncology Services-Auburn
🇺🇸Auburn, California, United States