Vemurafenib and Cobimetinib in Treating Patients With BRAF V600E Mutation Positive Craniopharyngioma
NCT ID: NCT03224767
Last Updated: 2025-02-18
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE2
24 participants
INTERVENTIONAL
2018-01-05
2028-08-01
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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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.
Vemurafenib
Given PO
Cobimetinib
Given PO
Laboratory Biomarker Analysis
Correlative studies
Quality-of-Life Assessment
Ancillary studies
Interventions
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Vemurafenib
Given PO
Cobimetinib
Given PO
Laboratory Biomarker Analysis
Correlative studies
Quality-of-Life Assessment
Ancillary studies
Eligibility Criteria
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Inclusion Criteria
* 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
* Bilirubin =\< 1.5 upper limit of normal (ULN)
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 ULN
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Alliance for Clinical Trials in Oncology
OTHER
Responsible Party
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Principal Investigators
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Priscilla K. Brastianos, MD
Role: STUDY_CHAIR
Massachusetts General Hospital
Locations
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University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
Sutter Cancer Centers Radiation Oncology Services-Auburn
Auburn, California, United States
Alta Bates Summit Medical Center-Herrick Campus
Berkeley, 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-Camino Division
Mountain View, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, 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 Roseville Medical Center
Roseville, California, United States
Sutter Medical Center Sacramento
Sacramento, 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
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
Tampa General Hospital
Tampa, Florida, United States
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 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
Kootenai Clinic Cancer Services - Post Falls
Post Falls, 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
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Bronson Battle Creek
Battle Creek, Michigan, United States
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Grand Rapids, Michigan, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, United States
Trinity Health Grand Rapids 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
University of Michigan Health - West
Wyoming, 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
Abbott-Northwestern Hospital
Minneapolis, Minnesota, United States
Hennepin County Medical Center
Minneapolis, Minnesota, United States
Health Partners Inc
Minneapolis, Minnesota, United States
Monticello Cancer Center
Monticello, Minnesota, United States
North Memorial Medical Health Center
Robbinsdale, Minnesota, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, United States
Regions Hospital
Saint Paul, 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
Ridgeview Medical Center
Waconia, Minnesota, United States
Rice Memorial Hospital
Willmar, Minnesota, United States
Minnesota Oncology Hematology PA-Woodbury
Woodbury, Minnesota, United States
Central Care Cancer Center - Bolivar
Bolivar, Missouri, United States
Research Medical Center
Kansas City, Missouri, United States
Washington University School of Medicine
St 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
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, United States
NYP/Weill Cornell Medical Center
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
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
M D Anderson Cancer Center
Houston, Texas, United States
Farmington Health Center
Farmington, Utah, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States
South Jordan Health Center
South Jordan, Utah, United States
Inova Schar Cancer Institute
Fairfax, Virginia, United States
FHCC South Lake Union
Seattle, Washington, United States
Fred Hutchinson Cancer Center
Seattle, Washington, United States
University of Washington Medical Center - Montlake
Seattle, Washington, United States
United Hospital Center
Bridgeport, West Virginia, United States
West Virginia University Healthcare
Morgantown, West Virginia, United States
Camden Clark Medical Center
Parkersburg, West Virginia, United States
Aurora Saint Luke's Medical Center
Milwaukee, Wisconsin, United States
Cancer Center of Western Wisconsin
New Richmond, Wisconsin, United States
Welch Cancer Center
Sheridan, Wyoming, United States
Countries
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References
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Brastianos PK, Twohy E, Geyer S, Gerstner ER, Kaufmann TJ, Tabrizi S, Kabat B, Thierauf J, Ruff MW, Bota DA, Reardon DA, Cohen AL, De La Fuente MI, Lesser GJ, Campian J, Agarwalla PK, Kumthekar P, Mann B, Vora S, Knopp M, Iafrate AJ, Curry WT Jr, Cahill DP, Shih HA, Brown PD, Santagata S, Barker FG 2nd, Galanis E. BRAF-MEK Inhibition in Newly Diagnosed Papillary Craniopharyngiomas. N Engl J Med. 2023 Jul 13;389(2):118-126. doi: 10.1056/NEJMoa2213329.
Rutenberg MS, Rotondo RL, Rao D, Holtzman AL, Indelicato DJ, Huh S, Morris CG, Mendenhall WM. Clinical outcomes following proton therapy for adult craniopharyngioma: a single-institution cohort study. J Neurooncol. 2020 Apr;147(2):387-395. doi: 10.1007/s11060-020-03432-9. Epub 2020 Feb 21.
Other Identifiers
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NCI-2017-00740
Identifier Type: REGISTRY
Identifier Source: secondary_id
A071601
Identifier Type: -
Identifier Source: org_study_id
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