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Vemurafenib and Cobimetinib in Treating Patients with BRAF V600E Mutation Positive Craniopharyngioma
Study Purpose
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.
Recruitment Criteria
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Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
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Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Interventional |
| Eligible Ages | 18 Years and Over |
| Gender | All |
- - Pre-registration: Patients must have local diagnosis of papillary craniopharyngioma and have tissue slides available for submission to central pathology review; central pathology review will include immunohistochemistry (IHC) testing for BRAF V600E mutation (VE1 clone) and beta-catenin IHC (membranous, non-nuclear pattern) if needed to confirm diagnosis of papillary craniopharyngioma.
- - Histologically proven papillary craniopharyngioma as documented by central pathology review with positive BRAF V600E mutation by IHC.
- - Measurable disease and/or non-measurable disease.
- - Measurable disease, defined as bidimensionally measurable lesions with clearly defined margins by magnetic resonance imaging (MRI) scans, with a minimum diameter of 10 mm in both dimensions.
- - Progressive disease required in cohort B, defined as an increase in the bidirectional area by 25% within the past 13 months after surgery or radiation; progressive or recurrent disease is not required in cohort A, but is allowed provided it is a new diagnosis and patient has not received prior treatment.
- - Prior treatment.
- - Cohort A: No prior therapy received other than surgery.
- - Cohort B: Prior radiation therapy required (any type of prior radiation is allowed) - For patients treated with external beam radiation therapy, interstitial brachytherapy or radiosurgery, an interval of >= 3 months must have elapsed from completion of radiation therapy to registration.
- - Recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or less toxicity attributed to radiation with exception of alopecia, fatigue.
- - For patients enrolling on Cohort A or Cohort B: - For patients treated with surgery, an interval of >= 21 days must have elapsed prior to registration.
- - No prior treatment with BRAF or MEK inhibitors.
- - Steroid dosing stable for at least 4 days prior to registration.
- - Not pregnant and not nursing; for women of childbearing potential only, a negative pregnancy test done =< 7 days prior to registration is required.
- - ECOG performance status =< 2.
- - Comorbid conditions.
- - No evidence of active bleeding, bleeding diathesis, or hemoptysis (>= 1/2 teaspoon of red blood) =< 8 weeks prior to registration.
- - No evidence of intracranial hemorrhage =< 4 weeks prior to registration.
- - Patients who have experienced thromboembolic event within 6 months prior to registration must be on stable therapeutic anticoagulation for at least 4 weeks prior to registration.
- - No symptomatic congestive heart failure (New York Heart Association class II, III, or IV) within 6 months prior to registration.
- - No current unstable angina or uncontrolled arrhythmia.
- - No uncontrolled hypertension at time of registration (blood pressure [BP] > 150/95 despite antihypertensive therapy) - No known history of prolonged QT syndrome.
- - No known history of ventricular arrhythmia within 6 months of registration.
- - No known history of uveitis or iritis =< 4 weeks prior to registration.
- - No known history of or evidence of retinal pathology that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion (RVO), or neovascular macular degeneration within 12 months of registration.
- - No known history of chronic lung disease.
- - Concomitant medications.
- - Chronic concomitant treatment with strong CYP3A4 inducers or CYP3A4 inhibitors is not allowed; patients must discontinue the drug at least 14 days prior to study registration.
- - Chronic concomitant treatment with CYP1A2 substrate is not allowed; patients must discontinue the drug at least 14 days prior to study registration.
- - Absolute neutrophil count >= 1500/mm^3.
- - Platelets >= 100,000/mm^3.
- - Creatinine =< 1.5 mg/dL OR creatinine clearance >= 45mL/min.
Trial Details
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Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT03224767 |
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Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
Phase 2 |
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Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
Alliance for Clinical Trials in Oncology |
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Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
Priscilla K. Brastianos, MD |
| Principal Investigator Affiliation | Massachusetts General Hospital |
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Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
Other, NIH |
| Overall Status | Active, not recruiting |
| Countries | United States |
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Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
BRAF V600E Mutation Present, Papillary Craniopharyngioma |
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.
- 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.
- 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.
Arms
Experimental: Treatment (vemurafenib, 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.
Interventions
Drug: - Vemurafenib
Given PO
Drug: - Cobimetinib
Given PO
Other: - Laboratory Biomarker Analysis
Correlative studies
Other: - Quality-of-Life Assessment
Ancillary studies
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
Status
Address
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Status
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Sutter Cancer Centers Radiation Oncology Services-Auburn
Auburn, California, 95603
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Alta Bates Summit Medical Center-Herrick Campus
Berkeley, California, 94704
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Mills-Peninsula Medical Center
Burlingame, California, 94010
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Address
Sutter Cancer Centers Radiation Oncology Services-Cameron Park
Cameron Park, California, 95682
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Address
Eden Hospital Medical Center
Castro Valley, California, 94546
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Address
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California, 90027
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Address
Memorial Medical Center
Modesto, California, 95355
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Address
Palo Alto Medical Foundation-Camino Division
Mountain View, California, 94040
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Address
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868
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Address
Palo Alto Medical Foundation Health Care
Palo Alto, California, 94301
Status
Address
Sutter Cancer Centers Radiation Oncology Services-Roseville
Roseville, California, 95661
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Address
Sutter Roseville Medical Center
Roseville, California, 95661
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Sutter Medical Center Sacramento
Sacramento, California, 95816
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California Pacific Medical Center-Pacific Campus
San Francisco, California, 94115
Status
Address
Palo Alto Medical Foundation-Sunnyvale
Sunnyvale, California, 94086
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Address
Sutter Cancer Centers Radiation Oncology Services-Vacaville
Vacaville, California, 95687
Status
Address
Sutter Solano Medical Center/Cancer Center
Vallejo, California, 94589
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Address
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, 06510
Status
Address
Yale University
New Haven, Connecticut, 06520
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Address
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, 06611
Status
Address
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
Status
Address
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Status
Address
Tampa General Hospital
Tampa, Florida, 33606
Status
Address
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706
Status
Address
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, 83605
Status
Address
Kootenai Health - Coeur d'Alene
Coeur D'Alene, Idaho, 83814
Status
Address
Idaho Urologic Institute-Meridian
Meridian, Idaho, 83642
Status
Address
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho, 83687
Status
Address
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, 83854
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Address
Rush University Medical Center
Chicago, Illinois, 60612
Status
Address
Central Care Cancer Center - Garden City
Garden City, Kansas, 67846
Status
Address
Central Care Cancer Center - Great Bend
Great Bend, Kansas, 67530
Status
Address
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Status
Address
Tufts Medical Center
Boston, Massachusetts, 02111
Status
Address
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Status
Address
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Status
Address
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
Status
Address
Bronson Battle Creek
Battle Creek, Michigan, 49017
Status
Address
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Grand Rapids, Michigan, 49503
Status
Address
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
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Address
Trinity Health Grand Rapids Hospital
Grand Rapids, Michigan, 49503
Status
Address
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007
Status
Address
West Michigan Cancer Center
Kalamazoo, Michigan, 49007
Status
Address
Borgess Medical Center
Kalamazoo, Michigan, 49048
Status
Address
Trinity Health Muskegon Hospital
Muskegon, Michigan, 49444
Status
Address
Corewell Health Lakeland Hospitals - Niles Hospital
Niles, Michigan, 49120
Status
Address
Cancer and Hematology Centers of Western Michigan - Norton Shores
Norton Shores, Michigan, 49444
Status
Address
Corewell Health Reed City Hospital
Reed City, Michigan, 49677
Status
Address
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
Saint Joseph, Michigan, 49085
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Address
Corewell Health Lakeland Hospitals - Saint Joseph Hospital
Saint Joseph, Michigan, 49085
Status
Address
Munson Medical Center
Traverse City, Michigan, 49684
Status
Address
University of Michigan Health - West
Wyoming, Michigan, 49519
Status
Address
Fairview Ridges Hospital
Burnsville, Minnesota, 55337
Status
Address
Minnesota Oncology - Burnsville
Burnsville, Minnesota, 55337
Status
Address
Mercy Hospital
Coon Rapids, Minnesota, 55433
Status
Address
Fairview Southdale Hospital
Edina, Minnesota, 55435
Status
Address
Unity Hospital
Fridley, Minnesota, 55432
Status
Address
Fairview Clinics and Surgery Center Maple Grove
Maple Grove, Minnesota, 55369
Status
Address
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, 55109
Status
Address
Saint John's Hospital - Healtheast
Maplewood, Minnesota, 55109
Status
Address
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407
Status
Address
Hennepin County Medical Center
Minneapolis, Minnesota, 55415
Status
Address
Health Partners Inc
Minneapolis, Minnesota, 55454
Status
Address
Monticello Cancer Center
Monticello, Minnesota, 55362
Status
Address
North Memorial Medical Health Center
Robbinsdale, Minnesota, 55422
Status
Address
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Status
Address
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416
Status
Address
Regions Hospital
Saint Paul, Minnesota, 55101
Status
Address
United Hospital
Saint Paul, Minnesota, 55102
Status
Address
Saint Francis Regional Medical Center
Shakopee, Minnesota, 55379
Status
Address
Lakeview Hospital
Stillwater, Minnesota, 55082
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Address
Ridgeview Medical Center
Waconia, Minnesota, 55387
Status
Address
Rice Memorial Hospital
Willmar, Minnesota, 56201
Status
Address
Minnesota Oncology Hematology PA-Woodbury
Woodbury, Minnesota, 55125
Status
Address
Central Care Cancer Center - Bolivar
Bolivar, Missouri, 65613
Status
Address
Research Medical Center
Kansas City, Missouri, 64132
Status
Address
Washington University School of Medicine
Saint Louis, Missouri, 63110
Status
Address
Billings Clinic Cancer Center
Billings, Montana, 59101
Status
Address
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715
Status
Address
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405
Status
Address
Great Falls Clinic
Great Falls, Montana, 59405
Status
Address
Kalispell Regional Medical Center
Kalispell, Montana, 59901
Status
Address
Community Medical Center
Missoula, Montana, 59804
Status
Address
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756
Status
Address
Rutgers New Jersey Medical School
Newark, New Jersey, 07101
Status
Address
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
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Address
NYP/Weill Cornell Medical Center
New York, New York, 10065
Status
Address
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Status
Address
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Status
Address
Cancer Centers of Southwest Oklahoma Research
Lawton, Oklahoma, 73505
Status
Address
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Status
Address
M D Anderson Cancer Center
Houston, Texas, 77030
Status
Address
Farmington Health Center
Farmington, Utah, 84025
Status
Address
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
Status
Address
South Jordan Health Center
South Jordan, Utah, 84009
Status
Address
Inova Schar Cancer Institute
Fairfax, Virginia, 22031
Status
Address
FHCC South Lake Union
Seattle, Washington, 98109
Status
Address
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
Status
Address
University of Washington Medical Center - Montlake
Seattle, Washington, 98195
Status
Address
United Hospital Center
Bridgeport, West Virginia, 26330
Status
Address
West Virginia University Healthcare
Morgantown, West Virginia, 26506
Status
Address
Camden Clark Medical Center
Parkersburg, West Virginia, 26101
Status
Address
Aurora Saint Luke's Medical Center
Milwaukee, Wisconsin, 53215
Status
Address
Cancer Center of Western Wisconsin
New Richmond, Wisconsin, 54017
Status
Address
Welch Cancer Center
Sheridan, Wyoming, 82801
