Don't get left behind! The modernized ClinicalTrials.gov is coming. Check it out now.
Say goodbye to ClinicalTrials.gov!
The new site is coming soon - go to the modernized ClinicalTrials.gov
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    A071601
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03224767
Recruitment Status : Recruiting
First Posted : July 21, 2017
Last Update Posted : April 4, 2023
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
BRAF V600E Mutation Present Papillary Craniopharyngioma Drug: Vemurafenib Drug: Cobimetinib Other: Laboratory Biomarker Analysis Other: Quality-of-Life Assessment Phase 2

Show Show detailed description
Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of BRAF/MEK Inhibitors in Papillary Craniopharyngiomas
Actual Study Start Date : August 4, 2017
Estimated Primary Completion Date : October 2023
Estimated Study Completion Date : August 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Treatment (vemurafenib, cobimetinib)
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.
 Drug: Vemurafenib
Given PO

Drug: Cobimetinib
Given PO

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Quality-of-Life Assessment
Ancillary studies


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Response rate [ Time Frame: Up to 5 years ]
    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.


Secondary Outcome Measures :
  1. Progression-free survival [ Time Frame: Up to 5 years ]
    Will be summarized for each cohort within each cohort with Kaplan-Meier curves and estimates.

  2. Overall survival [ Time Frame: Up to 5 years ]
    Will be summarized for each cohort within each cohort with Kaplan-Meier curves and estimates.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03224767


Contacts
Layout table for location contacts
Contact: Priscilla K. Brastianos, MD 617-643-1938 pbrastianos@partners.org

Locations
Show Show 104 study locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Study Chair: Priscilla K. Brastianos, MD Massachusetts General Hospital
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT03224767    
Other Study ID Numbers: A071601
NCI-2017-00740 ( Registry Identifier: NCI Clinical Trial Reporting Program )
U10CA180821 ( U.S. NIH Grant/Contract )
First Posted: July 21, 2017    Key Record Dates
Last Update Posted: April 4, 2023
Last Verified: April 2023

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Craniopharyngioma
Adamantinoma
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Bone Neoplasms
 Neoplasms by Site
Bone Diseases
Musculoskeletal Diseases
Vemurafenib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action