Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas
- Conditions
- Intracranial MeningiomaRecurrent MeningiomaNF2 Gene Mutation
- Interventions
- Registration Number
- NCT02523014
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
This phase II trial studies how well vismodegib, focal adhesion kinase (FAK) inhibitor GSK2256098, and capivasertib work in treating patients with meningioma that is growing, spreading, or getting worse (progressive). Vismodegib, FAK inhibitor GSK2256098, capivasertib, and abemaciclib 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 a SMO inhibitor in patients with meningiomas harboring SMO and PTCH1 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 NF2 mutations as measured by 6-month PFS and response rate.
III. To determine the activity of an AKT inhibitor in patients with meningiomas harboring AKT1/PIK3CA/PTEN mutations as measured by 6-month PFS and response rate.
IV. To determine the activity of a CDK inhibitor in patients with meningiomas harboring alterations in the CDK pathway or NF2 alterations as measured by 6-month PFS and response rate.
SECONDARY OBJECTIVES:
I. To determine overall survival and progression-free survival of SMO, FAK, AKT and CDK inhibitors in patients with meningioma.
II. To determine adverse event rates of SMO, FAK, AKT and CDK inhibitors in patients with meningioma.
III. To determine the activity of SMO, FAK, AKT and CDK inhibitors as measured by response rate by central radiology review.
OUTLINE: Patients are assigned to 1 of 4 treatment arms based on their mutation status.
ARM A (SMO/PTCH1 mutation): Patients receive vismodegib orally (PO) once daily (QD). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL FEBRUARY 2018)
ARM B (NF2 mutation): Patients receive FAK inhibitor GSK2256098 PO twice daily (BID). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL JULY 2017)
ARM C (AKT1, PIK3CA, or PTEN mutation): Patients receive capivasertib PO BID on days 1-4. Treatment repeats every 7 days for up to 1 cycle (28 days) in the absence of disease progression or unacceptable toxicity.
ARM D (CDK4, CDK6, CDKN2A, CCND1, CCND2, CCND3, CCNE1 alterations): Patients receive abemaciclib PO every 12 hours (Q12H). Cycles 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 124
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm D (abemaciclib) Abemaciclib Patients receive abemaciclib PO Q12H. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm C (capivasertib) Capivasertib Patients receive capivasertib PO BID on days 1-4. Treatment repeats every 7 days for up to 1 cycle (28 days) in the absence of disease progression or unacceptable toxicity. Arm B (FAK inhibitor GSK2256098) FAK Inhibitor GSK2256098 Patients receive FAK inhibitor GSK2256098 PO BID. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL JULY 2017) Arm A (vismodegib) Vismodegib Patients receive vismodegib PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL FEBRUARY 2018)
- Primary Outcome Measures
Name Time Method Response rate defined as a confirmed complete response (CR) or partial response (PR) Up to 2 years Point estimates will be generated for response rates within each treatment arm with corresponding 95% binomial confidence intervals.
Progression free survival (PFS) 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.
- Secondary Outcome Measures
Name Time Method Overall survival (OS) 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 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+.
Trial Locations
- Locations (767)
University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States
Anchorage Associates in Radiation Medicine
🇺🇸Anchorage, Alaska, United States
Anchorage Radiation Therapy Center
🇺🇸Anchorage, Alaska, United States
Alaska Breast Care and Surgery LLC
🇺🇸Anchorage, Alaska, United States
Alaska Oncology and Hematology LLC
🇺🇸Anchorage, Alaska, United States
Alaska Women's Cancer Care
🇺🇸Anchorage, Alaska, United States
Anchorage Oncology Centre
🇺🇸Anchorage, Alaska, United States
Katmai Oncology Group
🇺🇸Anchorage, Alaska, United States
Providence Alaska Medical Center
🇺🇸Anchorage, Alaska, United States
Kingman Regional Medical Center
🇺🇸Kingman, Arizona, United States
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