Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients with Progressive Meningiomas

Summary

Objectives

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.

CORRELATIVE SCIENCE OBJECTIVES:
I. To evaluate genetic and histological biomarkers in meningioma that are associated with treatment response, toxicity, and/or clinical variables, as well circulating/cell-free biomarkers.
II. To evaluate dynamic contrast enhanced magnetic resonance imaging (MRI) during treatment with SMO, FAK, AKT and CDK inhibitors for meningioma.
III. To evaluate volumetric response 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. Patients undergo magnetic resonance imaging (MRI) or computed tomography (CT) and may undergo blood sample collection throughout the trial. (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. Patients undergo MRI or CT and may undergo blood sample collection throughout the trial. (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. Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening and as clinically indicated throughout the trial. Patients also undergo MRI or CT and may undergo blood sample collection throughout the trial.

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. Patients undergo MRI or CT and may undergo blood sample collection throughout the trial. (CLOSED TO ACCRUAL OCTOBER 2022)

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