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Summary

for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
Jennie W. Taylor

Description

Summary

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.

Official Title

Phase II Trial of SMO/AKT/NF2 Inhibitors in Progressive Meningiomas With SMO/AKT/NF2 Mutations

Details

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.

Keywords

Intracranial Meningioma Recurrent Meningioma NF2 Gene Mutation

Eligibility

For people ages 18 years and up

  • 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)

Locations

  • California Pacific Medical Center-Pacific Campus accepting new patients
    San Francisco, California, 94115, United States
  • Kaiser Permanente-San Francisco accepting new patients
    San Francisco, California, 94115, United States
  • Kaiser Permanente accepting new patients
    Fresno, California, 93720, United States
  • Kaiser Permanente-South San Francisco accepting new patients
    South San Francisco, California, 94080, United States
  • Alta Bates Summit Medical Center-Herrick Campus accepting new patients
    Berkeley, California, 94704, United States
  • Kaiser Permanente-Richmond accepting new patients
    Richmond, California, 94801, United States
  • Mills-Peninsula Medical Center accepting new patients
    Burlingame, California, 94010, United States
  • Kaiser Permanente-Oakland accepting new patients
    Oakland, California, 94611, United States
  • Kaiser Permanente San Leandro accepting new patients
    San Leandro, California, 94577, United States
  • Kaiser Permanente-San Rafael accepting new patients
    San Rafael, California, 94903, United States
  • Eden Hospital Medical Center accepting new patients
    Castro Valley, California, 94546, United States
  • Kaiser Permanente-Redwood City accepting new patients
    Redwood City, California, 94063, United States
  • Kaiser Permanente-Walnut Creek accepting new patients
    Walnut Creek, California, 94596, United States
  • Sutter Cancer Research Consortium accepting new patients
    Novato, California, 94945, United States
  • Palo Alto Medical Foundation Health Care accepting new patients
    Palo Alto, California, 94301, United States
  • Kaiser Permanente-Vallejo accepting new patients
    Vallejo, California, 94589, United States
  • Sutter Solano Medical Center/Cancer Center accepting new patients
    Vallejo, California, 94589, United States
  • Kaiser Permanente-Fremont accepting new patients
    Fremont, California, 94538, United States
  • Palo Alto Medical Foundation-Fremont accepting new patients
    Fremont, California, 94538, United States
  • Palo Alto Medical Foundation-Camino Division accepting new patients
    Mountain View, California, 94040, United States
  • Palo Alto Medical Foundation-Gynecologic Oncology accepting new patients
    Mountain View, California, 94040, United States
  • Palo Alto Medical Foundation-Sunnyvale accepting new patients
    Sunnyvale, California, 94086, United States
  • Kaiser Permanente Medical Center - Santa Clara accepting new patients
    Santa Clara, California, 95051, United States
  • Kaiser Permanente-Deer Valley Medical Center accepting new patients
    Antioch, California, 94531, United States
  • Sutter Cancer Centers Radiation Oncology Services-Vacaville accepting new patients
    Vacaville, California, 95687, United States
  • Kaiser Permanente Medical Center-Vacaville accepting new patients
    Vacaville, California, 95688, United States
  • Kaiser Permanente-Santa Teresa-San Jose accepting new patients
    San Jose, California, 95119, United States
  • Kaiser Permanente-Santa Rosa accepting new patients
    Santa Rosa, California, 95403, United States
  • Sutter Pacific Medical Foundation currently not accepting new patients, but might later
    Santa Rosa, California, 95403, United States
  • Palo Alto Medical Foundation-Santa Cruz accepting new patients
    Santa Cruz, California, 95065, United States
  • Kaiser Permanente-Stockton accepting new patients
    Stockton, California, 95210, United States
  • Sutter Davis Hospital accepting new patients
    Davis, California, 95616, United States
  • Kaiser Permanente-South Sacramento accepting new patients
    Sacramento, California, 95823, United States
  • Sutter Medical Center Sacramento accepting new patients
    Sacramento, California, 95816, United States
  • Kaiser Permanente-Modesto accepting new patients
    Modesto, California, 95356, United States
  • Kaiser Permanente - Sacramento accepting new patients
    Sacramento, California, 95825, United States
  • Memorial Medical Center currently not accepting new patients, but might later
    Modesto, California, 95355, United States
  • Kaiser Permanente-Roseville accepting new patients
    Roseville, California, 95661, United States
  • Sutter Cancer Centers Radiation Oncology Services-Roseville accepting new patients
    Roseville, California, 95661, United States
  • Sutter Roseville Medical Center accepting new patients
    Roseville, California, 95661, United States
  • Sutter Cancer Centers Radiation Oncology Services-Cameron Park accepting new patients
    Cameron Park, California, 95682, United States
  • Sutter Cancer Centers Radiation Oncology Services-Auburn accepting new patients
    Auburn, California, 95603, United States
  • Sutter Auburn Faith Hospital accepting new patients
    Auburn, California, 95602, United States
  • PCR Oncology accepting new patients
    Pismo Beach, California, 93449, United States
  • Carson Tahoe Regional Medical Center accepting new patients
    Carson City, Nevada, 89703, United States
  • Renown Regional Medical Center accepting new patients
    Reno, Nevada, 89502, United States
  • Saint Mary's Regional Medical Center accepting new patients
    Reno, Nevada, 89503, United States
  • Providence Saint Joseph Medical Center/Disney Family Cancer Center accepting new patients
    Burbank, California, 91505, United States
  • Kaiser Permanente Los Angeles Medical Center accepting new patients
    Los Angeles, California, 90027, United States
  • Keck Medical Center of USC Pasadena accepting new patients
    Pasadena, California, 91105, United States
  • Los Angeles County-USC Medical Center accepting new patients
    Los Angeles, California, 90033, United States
  • USC / Norris Comprehensive Cancer Center accepting new patients
    Los Angeles, California, 90033, United States
  • UC Irvine Health/Chao Family Comprehensive Cancer Center accepting new patients
    Orange, California, 92868, United States
  • USC Norris Oncology/Hematology-Newport Beach accepting new patients
    Newport Beach, California, 92663, United States
  • Comprehensive Cancer Centers of Nevada-Summerlin accepting new patients
    Las Vegas, Nevada, 89144, United States
  • Summerlin Hospital Medical Center accepting new patients
    Las Vegas, Nevada, 89144, United States
  • HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills accepting new patients
    Las Vegas, Nevada, 89149, United States
  • Ann M Wierman MD LTD accepting new patients
    Las Vegas, Nevada, 89128, United States
  • Cancer and Blood Specialists-Tenaya accepting new patients
    Las Vegas, Nevada, 89128, United States
  • Comprehensive Cancer Centers of Nevada - Northwest accepting new patients
    Las Vegas, Nevada, 89128, United States
  • HealthCare Partners Medical Group Oncology/Hematology-Tenaya accepting new patients
    Las Vegas, Nevada, 89128, United States
  • Las Vegas Cancer Center-Medical Center accepting new patients
    Las Vegas, Nevada, 89148-2405, United States
  • 21st Century Oncology - Fort Apache accepting new patients
    Las Vegas, Nevada, 89148, United States
  • Comprehensive Cancer Centers of Nevada accepting new patients
    Las Vegas, Nevada, 89148, United States
  • Nevada Cancer Specialists-Fort Apache accepting new patients
    Las Vegas, Nevada, 89148, United States
  • HealthCare Partners Medical Group Oncology/Hematology-San Martin accepting new patients
    Las Vegas, Nevada, 89113, United States
  • University Medical Center of Southern Nevada accepting new patients
    Las Vegas, Nevada, 89102, United States
  • Cancer and Blood Specialists-Shadow accepting new patients
    Las Vegas, Nevada, 89106, United States
  • Radiation Oncology Centers of Nevada Central accepting new patients
    Las Vegas, Nevada, 89106, United States
  • 21st Century Oncology - Vegas Tenaya accepting new patients
    Las Vegas, Nevada, 89182, United States
  • 21st Century Oncology accepting new patients
    Las Vegas, Nevada, 89109, United States
  • HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway accepting new patients
    Las Vegas, Nevada, 89109, United States
  • Comprehensive Cancer Centers of Nevada - Central Valley accepting new patients
    Las Vegas, Nevada, 89169, United States
  • University Cancer Center accepting new patients
    Las Vegas, Nevada, 89169, United States
  • Radiation Oncology Centers of Nevada Southeast accepting new patients
    Las Vegas, Nevada, 89119, United States
  • Cancer and Blood Specialists-Henderson accepting new patients
    Henderson, Nevada, 89052, United States
  • Comprehensive Cancer Centers of Nevada - Henderson accepting new patients
    Henderson, Nevada, 89052, United States
  • Las Vegas Cancer Center-Henderson accepting new patients
    Henderson, Nevada, 89052, United States
  • Cancer Therapy and Integrative Medicine accepting new patients
    Las Vegas, Nevada, 89121, United States
  • 21st Century Oncology - Henderson accepting new patients
    Henderson, Nevada, 89074, United States
  • Comprehensive Cancer Centers of Nevada-Southeast Henderson accepting new patients
    Henderson, Nevada, 89074, United States

Details

Status
accepting new patients
Start Date
Sponsor
Alliance for Clinical Trials in Oncology
ID
NCT02523014
Phase
Phase 2
Lead Scientist
Jennie W. Taylor
Study Type
Interventional
Last Updated
August 1, 2017