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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
First received
Last updated
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
Health authority
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

Study Design


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
See also
  Status Clinical Trial Phase
Recruiting NCT04061980 - Encorafenib and Binimetinib With or Without Nivolumab in Treating Patients With Metastatic Radioiodine Refractory BRAF V600 Mutant Thyroid Cancer Phase 2
Active, not recruiting NCT02097225 - Onalespib, Dabrafenib, and Trametinib in Treating Patients With BRAF-Mutant Melanoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery Phase 1
Terminated NCT01940809 - Ipilimumab With or Without Dabrafenib, Trametinib, and/or Nivolumab in Treating Patients With Melanoma That Is Metastatic or Cannot Be Removed by Surgery Phase 1