Vemurafenib and Cobimetinib in Treating Patients with BRAF V600E Mutation Positive Craniopharyngioma

Status: Active

Description

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.

Eligibility Criteria

Inclusion Criteria

  • 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 and 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 and 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, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects; therefore, for women of childbearing potential only, a negative pregnancy test done =< 7 days prior to registration is required
  • Eastern Cooperative Oncology Group (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 >= 45 mL/min
  • Bilirubin =< 1.5 upper limit of normal (ULN)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 ULN

Locations & Contacts

Alabama

Birmingham
University of Alabama at Birmingham Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 205-934-0220
Email: tmyrick@uab.edu

California

Auburn
Sutter Cancer Centers Radiation Oncology Services-Auburn
Status: Active
Contact: Site Public Contact
Phone: 415-209-2686
Email: bernicl@sutterhealth.org
Berkeley
Alta Bates Summit Medical Center-Herrick Campus
Status: Active
Contact: Site Public Contact
Phone: 415-209-2686
Email: bernicl@sutterhealth.org
Burlingame
Mills-Peninsula Medical Center
Status: Active
Contact: Site Public Contact
Phone: 415-209-2686
Email: bernicl@sutterhealth.org
Cameron Park
Sutter Cancer Centers Radiation Oncology Services-Cameron Park
Status: Active
Contact: Site Public Contact
Phone: 415-209-2686
Email: bernicl@sutterhealth.org
Castro Valley
Eden Hospital Medical Center
Status: Active
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Phone: 415-209-2686
Email: bernicl@sutterhealth.org
Modesto
Memorial Medical Center
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Email: bernicl@sutterhealth.org
Mountain View
Palo Alto Medical Foundation-Camino Division
Status: Active
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Phone: 415-209-2686
Email: bernicl@sutterhealth.org
Orange
UC Irvine Health / Chao Family Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 877-827-8839
Email: ucstudy@uci.edu
Palo Alto
Palo Alto Medical Foundation Health Care
Status: Active
Contact: Site Public Contact
Phone: 415-209-2686
Email: bernicl@sutterhealth.org
Roseville
Sutter Cancer Centers Radiation Oncology Services-Roseville
Status: Active
Contact: Site Public Contact
Phone: 415-209-2686
Email: bernicl@sutterhealth.org
Sutter Roseville Medical Center
Status: Active
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Email: bernicl@sutterhealth.org
Sacramento
Sutter Medical Center Sacramento
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Email: bernicl@sutterhealth.org
San Francisco
California Pacific Medical Center-Pacific Campus
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Email: bernicl@sutterhealth.org
Sunnyvale
Palo Alto Medical Foundation-Sunnyvale
Status: Active
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Phone: 415-209-2686
Email: bernicl@sutterhealth.org
Vacaville
Sutter Cancer Centers Radiation Oncology Services-Vacaville
Status: Active
Contact: Site Public Contact
Phone: 415-209-2686
Email: bernicl@sutterhealth.org
Vallejo
Sutter Solano Medical Center / Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 415-209-2686
Email: bernicl@sutterhealth.org

Connecticut

New Haven
Smilow Cancer Center / Yale-New Haven Hospital
Status: Active
Contact: Site Public Contact
Phone: 203-785-5702
Email: canceranswers@yale.edu
Yale University
Status: Active
Contact: Site Public Contact
Phone: 203-785-5702
Email: canceranswers@yale.edu
Trumbull
Smilow Cancer Hospital Care Center-Trumbull
Status: Active
Contact: Site Public Contact
Phone: 203-785-5702
Email: canceranswers@yale.edu

Florida

Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 305-243-2647

Idaho

Boise
Saint Alphonsus Cancer Care Center-Boise
Status: Active
Contact: Site Public Contact
Phone: 734-712-3671
Email: stephanie.couch@stjoeshealth.org
Caldwell
Saint Alphonsus Cancer Care Center-Caldwell
Status: Active
Contact: Site Public Contact
Phone: 734-712-3671
Email: stephanie.couch@stjoeshealth.org
Coeur D'Alene
Kootenai Medical Center
Status: Active
Contact: Site Public Contact
Phone: 406-969-6060
Email: mccinfo@mtcancer.org
Meridian
Idaho Urologic Institute-Meridian
Status: Active
Contact: Site Public Contact
Phone: 734-712-3671
Email: stephanie.couch@stjoeshealth.org
Post Falls
Kootenai Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 406-969-6060
Email: mccinfo@mtcancer.org

Illinois

Chicago
Rush University Medical Center
Status: Active
Contact: Site Public Contact
Phone: 312-942-5498
Email: clinical_trials@rush.edu

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 410-955-8804
Email: jhcccro@jhmi.edu

Massachusetts

Boston
Dana-Farber Cancer Institute
Status: Active
Contact: Site Public Contact
Phone: 877-442-3324
Massachusetts General Hospital Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 877-726-5130

Michigan

Battle Creek
Bronson Battle Creek
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Grand Rapids
Helen DeVos Children's Hospital at Spectrum Health
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Mercy Health Saint Mary's
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Spectrum Health at Butterworth Campus
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Kalamazoo
Borgess Medical Center
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Bronson Methodist Hospital
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
West Michigan Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Muskegon
Mercy Health Mercy Campus
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Niles
Lakeland Hospital Niles
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Norton Shores
Cancer and Hematology Centers of Western Michigan - Norton Shores
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: connie.szczepanek@crcwm.org
Reed City
Spectrum Health Reed City Hospital
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Saint Joseph
Lakeland Medical Center Saint Joseph
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Marie Yeager Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Traverse City
Munson Medical Center
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Wyoming
Metro Health Hospital
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org

Minnesota

Burnsville
Fairview Ridges Hospital
Status: Active
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Coon Rapids
Mercy Hospital
Status: Active
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Edina
Fairview-Southdale Hospital
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Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Fridley
Unity Hospital
Status: Active
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Maple Grove
Fairview Maple Grove Medical Center
Status: Active
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Maplewood
Minnesota Oncology Hematology PA-Maplewood
Status: Active
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Saint John's Hospital - Healtheast
Status: Active
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Minneapolis
Abbott-Northwestern Hospital
Status: Active
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Health Partners Inc
Status: Active
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Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Hennepin County Medical Center
Status: Active
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Monticello
Monticello Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Robbinsdale
North Memorial Medical Health Center
Status: Active
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Rochester
Mayo Clinic
Status: Active
Contact: Site Public Contact
Phone: 855-776-0015
Saint Louis Park
Park Nicollet Clinic - Saint Louis Park
Status: Active
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Saint Paul
Regions Hospital
Status: Active
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
United Hospital
Status: Active
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Shakopee
Saint Francis Regional Medical Center
Status: Active
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Stillwater
Lakeview Hospital
Status: Active
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Waconia
Ridgeview Medical Center
Status: Active
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Willmar
Rice Memorial Hospital
Status: Active
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Woodbury
Minnesota Oncology Hematology PA-Woodbury
Status: Active
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com

Missouri

Saint Louis
Washington University School of Medicine
Status: Active
Contact: Site Public Contact
Phone: 800-600-3606
Email: info@siteman.wustl.edu

Montana

Billings
Billings Clinic Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-996-2663
Email: research@billingsclinic.org
Bozeman
Bozeman Deaconess Hospital
Status: Active
Contact: Site Public Contact
Phone: 406-969-6060
Email: mccinfo@mtcancer.org
Great Falls
Benefis Healthcare- Sletten Cancer Institute
Status: Active
Contact: Site Public Contact
Phone: 406-969-6060
Email: mccinfo@mtcancer.org
Kalispell
Kalispell Regional Medical Center
Status: Active
Contact: Site Public Contact
Phone: 406-969-6060
Email: mccinfo@mtcancer.org
Missoula
Community Medical Hospital
Status: Active
Contact: Site Public Contact
Phone: 406-969-6060
Email: mccinfo@mtcancer.org

New Jersey

Newark
Rutgers New Jersey Medical School
Status: Active
Contact: Site Public Contact
Phone: 732-235-8675

New York

New York
NYP / Weill Cornell Medical Center
Status: Active
Contact: Site Public Contact
Phone: 212-746-1848

North Carolina

Winston-Salem
Wake Forest University Health Sciences
Status: Active
Contact: Site Public Contact
Phone: 336-713-6771

Texas

Houston
M D Anderson Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 877-632-6789
Email: askmdanderson@mdanderson.org

Utah

Farmington
Farmington Health Center
Status: Active
Contact: Site Public Contact
Phone: 888-424-2100
Email: cancerinfo@hci.utah.edu
Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: Active
Contact: Site Public Contact
Phone: 888-424-2100
Email: cancerinfo@hci.utah.edu
South Jordan
South Jordan Health Center
Status: Active
Contact: Site Public Contact
Phone: 888-424-2100
Email: cancerinfo@hci.utah.edu

Washington

Seattle
Fred Hutchinson Cancer Research Center
Status: Active
Contact: Site Public Contact
Phone: 800-804-8824
Seattle Cancer Care Alliance
Status: Active
Contact: Site Public Contact
Phone: 800-804-8824
University of Washington Medical Center
Status: Active
Contact: Site Public Contact
Phone: 800-804-8824

Wisconsin

Milwaukee
Aurora Saint Luke's Medical Center
Status: Active
Contact: Site Public Contact
Phone: 414-302-2304
Email: ncorp@aurora.org
New Richmond
Cancer Center of Western Wisconsin
Status: Active
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com

Trial Objectives and Outline

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.

EXPLORATORY 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.

CORRELATIVE SCIENCE OBJECTIVES:

I. To evaluate molecular biomarkers of response in papillary craniopharyngiomas.

II. 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 cycles 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.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Alliance for Clinical Trials in Oncology

Principal Investigator
Priscilla Kaliopi Brastianos

Trial IDs

Primary ID A071601
Secondary IDs NCI-2017-00740
Clinicaltrials.gov ID NCT03224767