Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

Vismodegib and FAK Inhibitor GSK2256098 in Treating Patients With Progressive Meningiomas

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2017 by Alliance for Clinical Trials in Oncology
Sponsor:
Collaborators:
National Cancer Institute (NCI)
GlaxoSmithKline
Genentech, Inc.
Brain Science Foundation
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT02523014
First received: August 11, 2015
Last updated: May 2, 2017
Last verified: May 2017
  Purpose
This phase II trial studies how well vismodegib and focal adhesion kinase (FAK) inhibitor GSK2256098 work in treating patients with meningioma that is growing, spreading, or getting worse. Vismodegib and FAK inhibitor GSK2256098 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition Intervention Phase
Intracranial Meningioma
Recurrent Meningioma
NF2 Gene Mutation
Drug: vismodegib
Drug: GSK2256098
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Phase II Trial of SMO/AKT/NF2 Inhibitors in Progressive Meningiomas With SMO/AKT/NF2 Mutations

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Progression free survival (PFS) [ Time Frame: At 6 months ]
    Point estimates and 95% binomial confidence intervals will be generated for the six month PFS rate within each cohort of each treatment arm. Kaplan-Meier curves will be generated for PFS for each cohort within each treatment arm.

  • Response rate defined as a confirmed complete response (CR) or partial response (PR) [ Time Frame: Up to 2 years ]
    Point estimates will be generated for response rates within each treatment arm with corresponding 95% binomial confidence intervals.


Secondary Outcome Measures:
  • Overall survival (OS) [ Time Frame: Up to 2 years ]
    OS will be summarized for each cohort within each treatment group with Kaplan-Meier curves and estimates.

  • Incidence of adverse events according to National Cancer Institute CTCAE version 4.0 [ Time Frame: Up to 4 weeks after completion of study treatment ]
    Adverse events (AEs) will be summarized for each treatment group. They will be summarized as the number and frequency of each event. In addition the AEs will be summarized as the number and frequency of patients who experience any AE, AEs of grade 3+, and AEs of grade 4+.


Estimated Enrollment: 69
Study Start Date: August 2015
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A - vismodegib
Patients receive vismodegib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: vismodegib
Given PO
Experimental: Arm B - GSK2256098
Patients receive FAK inhibitor GSK2256098 PO BID. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: GSK2256098
Given PO

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the activity of a smoothened, frizzled class receptor (SMO) and PTCH1 inhibitor in patients with meningiomas harboring SMO mutations as measured by 6-month progression free survival (PFS) and response rate.

II. To determine the activity of a FAK inhibitor in patients with meningiomas harboring neurofibromin 2 (NF2) mutations as measured by 6-month PFS and response rate.

SECONDARY OBJECTIVES:

I. To determine overall survival and progression-free survival of SMO and FAK inhibitors in patients with meningioma.

II. To determine adverse event rates of SMO and FAK inhibitors in patients with meningioma.

III. To determine the activity of SMO and FAK inhibitor as measured by response rate by central radiology review.

TERTIARY OBJECTIVES:

I. To evaluate genetic biomarkers in meningioma. II. To evaluate dynamic contrast enhanced magnetic resonance imaging (MRI) during treatment with SMO and FAK inhibitors for meningioma.

III. To evaluate volumetric response by central radiology review.

OUTLINE: Patients are assigned to 1 of 2 treatment arms based on their mutation status.

ARM A (SMO/PTCH1 mutation): Patients receive vismodegib orally (PO) once daily (QD). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B (NF2 mutation): Patients receive FAK inhibitor GSK2256098 PO twice daily (BID). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for a maximum of 5 years from registration.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • Documentation of disease:

    • Histologic documentation: histologically proven intracranial meningioma as documented by central pathology review
    • Molecular documentation: presence of SMO, PTCH1 or NF2 mutation in tumor sample as documented by central laboratory
    • Progressive OR residual disease, as defined by the following:

      • Residual measurable disease: residual measurable disease immediately after surgery without requirement for progression; for grade I disease, progression pre-operatively needs to be documented, with an increase in size of the measurable primary lesion on imaging by 25% or more (bidirectional area); the change must occur between scans separated by no more than 12 months; residual measurable disease will be defined by bidimensionally measurable lesions with clearly defined margins by MRI scans, with a minimum diameter of 10 mm in both dimensions
      • Progressive measurable disease: progression defined as an increase in size of the measurable primary lesion on imaging by 25% or more (bidirectional area); the change must occur between scans separated by no more than 12 months
      • Post radiation patients: patients with measurable and progressive meningioma who have received radiation are potentially eligible, but need to show evidence of progressive disease after completion of radiation; at least 24 weeks must have elapsed from completion of radiation to registration
  • Measurable disease: measurable disease is defined by a bidimensionally measurable main lesion on MRI or computed tomography (CT) images (MRI preferred) with clearly defined margins; multifocal disease is allowed
  • Prior treatment

    • Prior medical therapy is allowed but not required
    • No limit on number of prior therapies
    • No chemotherapy, other investigational agents within 28 days of study treatment
    • No other concurrent investigational agents or other meningioma-directed therapy (chemotherapy, radiation) while on study
    • For patients treated with external beam radiation, interstitial brachytherapy or radiosurgery, an interval > 24 weeks must have elapsed from completion of radiation therapy to registration
    • Steroid dosing stable for at least 4 days
    • Recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or less toxicity from other agents with exception of alopecia and fatigue
    • No craniotomy within 28 days of registration
  • Not pregnant and not nursing:

    * A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)

  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Patient history:

    • Patients with history of neurofibromatosis (NF) may have other stable central nervous system (CNS) tumors (schwannoma, acoustic neuroma or ependymoma) if lesions have been stable for 6 months
    • No metastatic meningiomas (as defined by extracranial meningiomas) allowed
    • No history of allergic reactions attributed to compounds of similar or biologic composition to assigned study drug
    • No known active hepatitis B or C
    • No current Child Pugh class B or C liver disease
    • No uncontrolled gastric ulcer disease (grade 3 gastric ulcer disease within 28 days of registration)
    • No uncontrolled diabetes defined as a known diabetic with hemoglobin A1C (HBA1C) > 7.5 OR fasting glucose > 140
    • No uncontrolled hypertension defined as blood pressure (BP) > 140/90
    • No abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 28 days prior to registration
  • Concomitant medications:

    • Chronic concomitant treatment with strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors must discontinue the drug for 14 days prior to registration on the study for patients with NF2 mutation enrolled to GSK2256098
    • Chronic concomitant treatment with strong CYP3A4 inducers is not allowed; patients must discontinue the drug 14 days prior to the start of study treatment for patients with NF2 mutation enrolled to GSK2256098
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Creatinine OR =< 1.5 mg/dl x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance > 45 mL/min
  • Urine protein:creatinine ratio (UPC) =< 45 mg/mmol; ONLY APPLICABLE for patients with NF2 mutation (GSK2256098)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN); except in case of Gilbert's disease
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
  • Fasting triglyceride =< 200 mg/dL; ONLY APPLICABLE for patients with NF2 mutation (GSK2256098)
  • Fasting cholesterol =< 240 mg/dL; ONLY APPLICABLE for patients with NF2 mutation (GSK2256098)
  • Corrected QC interval calculated using Fridericia's formula (QTcF) =< 500 msec; ONLY APPLICABLE for patients with NF2 mutation (GSK2256098)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02523014

Contacts
Contact: Priscilla Brastianos, MD 617-643-1939

  Show 556 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
GlaxoSmithKline
Genentech, Inc.
Brain Science Foundation
Investigators
Study Chair: Priscilla Brastianos, MD Massachusetts General Hospital
  More Information

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT02523014     History of Changes
Other Study ID Numbers: A071401
NCI-2015-00546 ( Registry Identifier: NCI Clinical Trials Reporting Program )
Study First Received: August 11, 2015
Last Updated: May 2, 2017

Additional relevant MeSH terms:
Meningioma
Neoplasms, Nerve Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Vascular Tissue
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases

ClinicalTrials.gov processed this record on May 25, 2017