BRAF V600E Mutation PresentPhase 2NCT03224767
Vemurafenib and Cobimetinib in Treating Patients With BRAF V600E Mutation Positive Craniopharyngioma
A Phase 2 study testing Vemurafenib, Cobimetinib and Laboratory Biomarker Analysis in people with BRAF V600E Mutation Present and Papillary Craniopharyngioma, run by Alliance for Clinical Trials in Oncology at 106 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- BRAF V600E Mutation Present, Papillary Craniopharyngioma
- What is being tested?
- Vemurafenib, Cobimetinib and Laboratory Biomarker Analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 106 sitesUnited States
- Study dates
- 5 Jan 2018to 1 Aug 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
- 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 any progressive measurable disease 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 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
- 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
Trial locations and contacts
106 sites in 1 country.
106 sites in 1 country
United States106 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
Sutter Cancer Centers Radiation Oncology Services-Auburn
Auburn, California, 95603
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Bronson Battle Creek
Battle Creek, Michigan, 49017
Alta Bates Summit Medical Center-Herrick Campus
Berkeley, California, 94704
Billings Clinic Cancer Center
Billings, Montana, 59101
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706
Central Care Cancer Center - Bolivar
Bolivar, Missouri, 65613
Tufts Medical Center
Boston, Massachusetts, 02111
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715
United Hospital Center
Bridgeport, West Virginia, 26330
Mills-Peninsula Medical Center
Burlingame, California, 94010
Fairview Ridges Hospital
Burnsville, Minnesota, 55337
Minnesota Oncology - Burnsville
Burnsville, Minnesota, 55337
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, 83605
Sutter Cancer Centers Radiation Oncology Services-Cameron Park
Cameron Park, California, 95682
Eden Hospital Medical Center
Castro Valley, California, 94546
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Rush University Medical Center
Chicago, Illinois, 60612
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814
Mercy Hospital
Coon Rapids, Minnesota, 55433
Fairview Southdale Hospital
Edina, Minnesota, 55435
Inova Schar Cancer Institute
Fairfax, Virginia, 22031
Farmington Health Center
Farmington, Utah, 84025
Unity Hospital
Fridley, Minnesota, 55432
Central Care Cancer Center - Garden City
Garden City, Kansas, 67846
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Grand Rapids, Michigan, 49503
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
Trinity Health Grand Rapids Hospital
Grand Rapids, Michigan, 49503
Central Care Cancer Center - Great Bend
Great Bend, Kansas, 67530
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405
Great Falls Clinic
Great Falls, Montana, 59405
M D Anderson Cancer Center
Houston, Texas, 77030
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007
West Michigan Cancer Center
Kalamazoo, Michigan, 49007
Borgess Medical Center
Kalamazoo, Michigan, 49048
Kalispell Regional Medical Center
Kalispell, Montana, 59901
Research Medical Center
Kansas City, Missouri, 64132
Cancer Centers of Southwest Oklahoma Research
Lawton, Oklahoma, 73505
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California, 90027
Fairview Clinics and Surgery Center Maple Grove
Maple Grove, Minnesota, 55369
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, 55109
Saint John's Hospital - Healtheast
Maplewood, Minnesota, 55109
Idaho Urologic Institute-Meridian
Meridian, Idaho, 83642
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Aurora Saint Luke's Medical Center
Milwaukee, Wisconsin, 53215
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407
Hennepin County Medical Center
Minneapolis, Minnesota, 55415
Health Partners Inc
Minneapolis, Minnesota, 55454
Community Medical Center
Missoula, Montana, 59804
Memorial Medical Center
Modesto, California, 95355
Monticello Cancer Center
Monticello, Minnesota, 55362
West Virginia University Healthcare
Morgantown, West Virginia, 26506
Palo Alto Medical Foundation-Camino Division
Mountain View, California, 94040
Trinity Health Muskegon Hospital
Muskegon, Michigan, 49444
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho, 83687
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, 06510
Yale University
New Haven, Connecticut, 06520
Cancer Center of Western Wisconsin
New Richmond, Wisconsin, 54017
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
NYP/Weill Cornell Medical Center
New York, New York, 10065
Rutgers New Jersey Medical School
Newark, New Jersey, 07101
Corewell Health Lakeland Hospitals - Niles Hospital
Niles, Michigan, 49120
Cancer and Hematology Centers of Western Michigan - Norton Shores
Norton Shores, Michigan, 49444
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868
Palo Alto Medical Foundation Health Care
Palo Alto, California, 94301
Camden Clark Medical Center
Parkersburg, West Virginia, 26101
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, 83854
Corewell Health Reed City Hospital
Reed City, Michigan, 49677
North Memorial Medical Health Center
Robbinsdale, Minnesota, 55422
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Sutter Cancer Centers Radiation Oncology Services-Roseville
Roseville, California, 95661
Sutter Roseville Medical Center
Roseville, California, 95661
Sutter Medical Center Sacramento
Sacramento, California, 95816
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
Saint Joseph, Michigan, 49085
Corewell Health Lakeland Hospitals - Saint Joseph Hospital
Saint Joseph, Michigan, 49085
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416
Regions Hospital
Saint Paul, Minnesota, 55101
United Hospital
Saint Paul, Minnesota, 55102
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
California Pacific Medical Center-Pacific Campus
San Francisco, California, 94115
FHCC South Lake Union
Seattle, Washington, 98109
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
University of Washington Medical Center - Montlake
Seattle, Washington, 98195
Saint Francis Regional Medical Center
Shakopee, Minnesota, 55379
Welch Cancer Center
Sheridan, Wyoming, 82801
South Jordan Health Center
South Jordan, Utah, 84009
Washington University School of Medicine
St Louis, Missouri, 63110
Lakeview Hospital
Stillwater, Minnesota, 55082
Palo Alto Medical Foundation-Sunnyvale
Sunnyvale, California, 94086
Tampa General Hospital
Tampa, Florida, 33606
Munson Medical Center
Traverse City, Michigan, 49684
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, 06611
Sutter Cancer Centers Radiation Oncology Services-Vacaville
Vacaville, California, 95687
Sutter Solano Medical Center/Cancer Center
Vallejo, California, 94589
Ridgeview Medical Center
Waconia, Minnesota, 55387
Rice Memorial Hospital
Willmar, Minnesota, 56201
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Minnesota Oncology Hematology PA-Woodbury
Woodbury, Minnesota, 55125
University of Michigan Health - West
Wyoming, Michigan, 49519
About this study
Official title: Phase II Trial of BRAF/MEK Inhibitors in Papillary Craniopharyngiomas
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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:
- 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.
- 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.
- Being tested
- Vemurafenib, Cobimetinib, Laboratory Biomarker Analysis, Quality-of-Life Assessment
- Medical subject headings
- Craniopharyngioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VemurafenibDrug
Given PO
CobimetinibDrug
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
Quality-of-Life AssessmentOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (vemurafenib, cobimetinib) | Experimental | 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. Receives: Drug: Vemurafenib; Drug: Cobimetinib; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate
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.
Measured: Up to 5 years
Secondary outcomes (2)
Progression-free Survival
Will be summarized for each cohort within each cohort with Kaplan-Meier curves and estimates at 12 months
Measured: Up to 1 year
Overall Survival
Will be summarized for each cohort within each cohort with Kaplan-Meier curves and estimates at 12 months.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2017
- Study start5 Jan 2018
- Primary completion22 Sep 2023
- Study completion1 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for BRAF V600E Mutation PresentStudies of the same condition, open and under way.
- More trials run by Alliance for Clinical Trials in OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alliance for Clinical Trials in Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Priscilla K. Brastianos, MD, Study chair, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03224767
- Sponsor's protocol ID
- A071601
- Other IDs
- NCI-2017-00740, U10CA180821
- Status last verified
- Jun 2026
- First submitted
- 19 Jul 2017
- Last updated
- 7 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Fudaba H, Yanagida M, Takao K, Onishi K, Matsuta H, Momii Y, Anan M, Hata N, Etoh T, Fujiki M. Quantitative BRAF p.V600E mutation monitoring in cerebrospinal fluid cell-free DNA reflects therapeutic response to BRAF/MEK inhibitors in papillary craniopharyngioma: a report of two cases. Acta Neuropathol Commun. 2026 May 4;14(1):134. doi: 10.1186/s40478-026-02314-x.
PubMed 42083012Brastianos 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.
PubMed 37437144Rutenberg 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.
PubMed 32086697