Clinical Trials /

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

NCT03224767

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.

Related Conditions:
  • Papillary Craniopharyngioma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Vemurafenib and Cobimetinib in Treating Patients With BRAF V600E Mutation Positive Craniopharyngioma
  • Official Title: Phase II Trial of BRAF/MEK Inhibitors in Papillary Craniopharyngiomas

Clinical Trial IDs

  • ORG STUDY ID: A071601
  • SECONDARY ID: NCI-2017-00740
  • SECONDARY ID: U10CA180821
  • NCT ID: NCT03224767

Conditions

  • BRAF V600E Mutation Present
  • Papillary Craniopharyngioma

Interventions

DrugSynonymsArms
VemurafenibTreatment (vemurafenib, cobimetinib)
CobimetinibTreatment (vemurafenib, cobimetinib)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (vemurafenib, cobimetinib)ExperimentalPatients 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.
  • Vemurafenib
  • Cobimetinib

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response rate
Time Frame:Up to 5 years
Safety Issue:
Description: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

Measure:Progression-free survival
Time Frame:Up to 5 years
Safety Issue:
Description:Will be summarized for each cohort within each cohort with Kaplan-Meier curves and estimates.
Measure:Overall survival
Time Frame:Up to 5 years
Safety Issue:
Description:Will be summarized for each cohort within each cohort with Kaplan-Meier curves and estimates.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Alliance for Clinical Trials in Oncology

Last Updated

August 4, 2017