Clinical trial NCT03224767: Vemurafenib and Cobimetinib in Treating Patients With BRAF V600E Mutation Positive Craniopharyngioma
Official title: Phase II Trial of BRAF/MEK Inhibitors in Papillary Craniopharyngiomas
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: BRAF V600E Mutation Present
Papillary Craniopharyngioma
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2017-07-21
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility 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 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

Primary outcomes:
measure: Response rate
timeFrame: Up to 5 years
Secondary outcomes:
measure: Progression-free survival
timeFrame: Up to 5 years
measure: Overall survival
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Cancer Center
state: Alabama
city: Auburn
country: United States
facility: Sutter Cancer Centers Radiation Oncology Services-Auburn
state: California
city: Berkeley
country: United States
facility: Alta Bates Summit Medical Center-Herrick Campus
state: California
city: Burlingame
country: United States
facility: Mills-Peninsula Medical Center
state: California
city: Cameron Park
country: United States
facility: Sutter Cancer Centers Radiation Oncology Services-Cameron Park
state: California
city: Castro Valley
country: United States
facility: Eden Hospital Medical Center
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles Medical Center
state: California
city: Modesto
country: United States
facility: Memorial Medical Center
state: California
city: Mountain View
country: United States
facility: Palo Alto Medical Foundation-Camino Division
state: California
city: Orange
country: United States
facility: UC Irvine Health/Chao Family Comprehensive Cancer Center
state: California
city: Palo Alto
country: United States
facility: Palo Alto Medical Foundation Health Care
state: California
city: Roseville
country: United States
facility: Sutter Cancer Centers Radiation Oncology Services-Roseville
state: California
city: Roseville
country: United States
facility: Sutter Roseville Medical Center
state: California
city: Sacramento
country: United States
facility: Sutter Medical Center Sacramento
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center-Pacific Campus
state: California
city: Sunnyvale
country: United States
facility: Palo Alto Medical Foundation-Sunnyvale
state: California
city: Vacaville
country: United States
facility: Sutter Cancer Centers Radiation Oncology Services-Vacaville
state: California
city: Vallejo
country: United States
facility: Sutter Solano Medical Center/Cancer Center
state: California
city: New Haven
country: United States
facility: Smilow Cancer Center/Yale-New Haven Hospital
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Trumbull
country: United States
facility: Smilow Cancer Hospital Care Center-Trumbull
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine-Sylvester Cancer Center
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Boise
country: United States
facility: Saint Alphonsus Cancer Care Center-Boise
state: Idaho
city: Caldwell
country: United States
facility: Saint Alphonsus Cancer Care Center-Caldwell
state: Idaho
city: Coeur D'Alene
country: United States
facility: Kootenai Health - Coeur d'Alene
state: Idaho
city: Meridian
country: United States
facility: Idaho Urologic Institute-Meridian
state: Idaho
city: Nampa
country: United States
facility: Saint Alphonsus Cancer Care Center-Nampa
state: Idaho
city: Post Falls
country: United States
facility: Kootenai Clinic Cancer Services - Post Falls
state: Idaho
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Garden City
country: United States
facility: Central Care Cancer Center - Garden City
state: Kansas
city: Great Bend
country: United States
facility: Central Care Cancer Center - Great Bend
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Cancer Center
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Battle Creek
country: United States
facility: Bronson Battle Creek
state: Michigan
city: Grand Rapids
country: United States
facility: Corewell Health Grand Rapids Hospitals - Butterworth Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Trinity Health Grand Rapids Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: Borgess Medical Center
state: Michigan
city: Muskegon
country: United States
facility: Trinity Health Muskegon Hospital
state: Michigan
city: Niles
country: United States
facility: Corewell Health Lakeland Hospitals - Niles Hospital
state: Michigan
city: Norton Shores
country: United States
facility: Cancer and Hematology Centers of Western Michigan - Norton Shores
state: Michigan
city: Reed City
country: United States
facility: Corewell Health Reed City Hospital
state: Michigan
city: Saint Joseph
country: United States
facility: Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
state: Michigan
city: Saint Joseph
country: United States
facility: Corewell Health Lakeland Hospitals - Saint Joseph Hospital
state: Michigan
city: Traverse City
country: United States
facility: Munson Medical Center
state: Michigan
city: Wyoming
country: United States
facility: University of Michigan Health - West
state: Michigan
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Burnsville
country: United States
facility: Minnesota Oncology - Burnsville
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy Hospital
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Unity Hospital
state: Minnesota
city: Maple Grove
country: United States
facility: Fairview Clinics and Surgery Center Maple Grove
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology Hematology PA-Maplewood
state: Minnesota
city: Maplewood
country: United States
facility: Saint John's Hospital - Healtheast
state: Minnesota
city: Minneapolis
country: United States
facility: Abbott-Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Minneapolis
country: United States
facility: Health Partners Inc
state: Minnesota
city: Monticello
country: United States
facility: Monticello Cancer Center
state: Minnesota
city: Robbinsdale
country: United States
facility: North Memorial Medical Health Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Saint Louis Park
country: United States
facility: Park Nicollet Clinic - Saint Louis Park
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Saint Paul
country: United States
facility: United Hospital
state: Minnesota
city: Shakopee
country: United States
facility: Saint Francis Regional Medical Center
state: Minnesota
city: Stillwater
country: United States
facility: Lakeview Hospital
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Willmar
country: United States
facility: Rice Memorial Hospital
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Oncology Hematology PA-Woodbury
state: Minnesota
city: Bolivar
country: United States
facility: Central Care Cancer Center - Bolivar
state: Missouri
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Billings
country: United States
facility: Billings Clinic Cancer Center
state: Montana
city: Bozeman
country: United States
facility: Bozeman Health Deaconess Hospital
state: Montana
city: Great Falls
country: United States
facility: Benefis Sletten Cancer Institute
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Community Medical Center
state: Montana
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
state: New Hampshire
city: Newark
country: United States
facility: Rutgers New Jersey Medical School
state: New Jersey
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center at NYU Langone
state: New York
city: New York
country: United States
facility: NYP/Weill Cornell Medical Center
state: New York
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Lawton
country: United States
facility: Cancer Centers of Southwest Oklahoma Research
state: Oklahoma
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Farmington
country: United States
facility: Farmington Health Center
state: Utah
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: South Jordan
country: United States
facility: South Jordan Health Center
state: Utah
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Seattle
country: United States
facility: FHCC South Lake Union
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center - Montlake
state: Washington
city: Bridgeport
country: United States
facility: United Hospital Center
state: West Virginia
city: Morgantown
country: United States
facility: West Virginia University Healthcare
state: West Virginia
city: Parkersburg
country: United States
facility: Camden Clark Medical Center
state: West Virginia
city: Milwaukee
country: United States
facility: Aurora Saint Luke's Medical Center
state: Wisconsin
city: New Richmond
country: United States
facility: Cancer Center of Western Wisconsin
state: Wisconsin
city: Sheridan
country: United States
facility: Welch Cancer Center
state: Wyoming
Study officials:
affiliation: Massachusetts General Hospital
name: Priscilla K. Brastianos, MD
role: STUDY_CHAIR
References:
citation: 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.