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

BRAF V600E Mutation Present Clinical Trial

Official title:

Phase II Trial of BRAF/MEK Inhibitors in Papillary Craniopharyngiomas

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03224767
• Other study ID #: A071601
• Secondary ID: NCI-2017-00740U1
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 4, 2017
• Est. completion date: August 2026

Study information

• Verified date: May 2024
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 24
• Est. completion date: August 2026
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

• 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

• Bilirubin =< 1.5 upper limit of normal (ULN)

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 ULN

Related Conditions & MeSH terms

• BRAF V600E Mutation Present
• Craniopharyngioma
• Papillary Craniopharyngioma

Intervention

Drug:
• Vemurafenib
Given PO
• Cobimetinib
Given PO

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Quality-of-Life Assessment
Ancillary studies

Locations

Country	Name	City	State
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Billings Clinic Cancer Center	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Bozeman Health Deaconess Hospital	Bozeman	Montana
United States	United Hospital Center	Bridgeport	West Virginia
United States	Mills-Peninsula Medical Center	Burlingame	California
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Minnesota Oncology - Burnsville	Burnsville	Minnesota
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California
United States	Eden Hospital Medical Center	Castro Valley	California
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	Farmington Health Center	Farmington	Utah
United States	Unity Hospital	Fridley	Minnesota
United States	Central Care Cancer Center - Garden City	Garden City	Kansas
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	Central Care Cancer Center - Great Bend	Great Bend	Kansas
United States	Benefis Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	M D Anderson Cancer Center	Houston	Texas
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Research Medical Center	Kansas City	Missouri
United States	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
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	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Health Partners Inc	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Community Medical Center	Missoula	Montana
United States	Memorial Medical Center	Modesto	California
United States	Monticello Cancer Center	Monticello	Minnesota
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Palo Alto Medical Foundation-Camino Division	Mountain View	California
United States	Trinity Health Muskegon Hospital	Muskegon	Michigan
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	Smilow Cancer Center/Yale-New Haven Hospital	New Haven	Connecticut
United States	Yale University	New Haven	Connecticut
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
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	Rutgers New Jersey Medical School	Newark	New Jersey
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	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
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	Camden Clark Medical Center	Parkersburg	West Virginia
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Corewell Health Reed City Hospital	Reed City	Michigan
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic in Rochester	Rochester	Minnesota
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	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	Washington University School of Medicine	Saint Louis	Missouri
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	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	California Pacific Medical Center-Pacific Campus	San Francisco	California
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	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Welch Cancer Center	Sheridan	Wyoming
United States	South Jordan Health Center	South Jordan	Utah
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California
United States	Tampa General Hospital	Tampa	Florida
United States	Munson Medical Center	Traverse City	Michigan
United States	Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut
United States	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California
United States	Sutter Solano Medical Center/Cancer Center	Vallejo	California
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	University of Michigan Health - West	Wyoming	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 5 years
Secondary	Progression-free survival	Will be summarized for each cohort within each cohort with Kaplan-Meier curves and estimates.	Up to 5 years
Secondary	Overall survival	Will be summarized for each cohort within each cohort with Kaplan-Meier curves and estimates.	Up to 5 years