Protocol Summary

Protocol No.: OCR15372

Sponsor Protocol No.: A071401

Study Title
Phase II Trial Of SMO/AKT/NF2 Inhibitors in Progressive Meningiomas with SMO/AKT/NF2 Mutations

Principal Investigator(s)
Tran, David

Objective
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.

Description
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.

Phase: Phase II

Age Group: Adult

Scope: National

Treatment
Arm A - vismodegib
Patients receive vismodegib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Arm B - GSK2256098
Patients receive FAK inhibitor GSK2256098 PO BID. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Detailed Eligibility
1. Ages 18 years old and older
2. Histologic documentation: histologically proven intracranial meningioma as documented by central pathology review
3. Molecular documentation: presence of SMO, PTCH1 or NF2 mutation in tumor sample as documented by central laboratory
4. 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
5. 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
6. Prior medical therapy is allowed but not required
7. No limit on number of prior therapies
8. No chemotherapy, other investigational agents within 28 days of study treatment
9. No other concurrent investigational agents or other meningioma-directed therapy (chemotherapy, radiation) while on study
10. 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
11. Steroid dosing stable for at least 4 days
12. Recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or less toxicity from other agents with exception of alopecia and fatigue
13. No craniotomy within 28 days of registration
14. 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)
15. Eastern Cooperative Oncology Group (ECOG) performance status =16. 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
17. No metastatic meningiomas (as defined by extracranial meningiomas) allowed
18. No history of allergic reactions attributed to compounds of similar or biologic composition to assigned study drug
19. No known active hepatitis B or C
20. No current Child Pugh class B or C liver disease
21. No uncontrolled gastric ulcer disease (grade 3 gastric ulcer disease within 28 days of registration)
22. No uncontrolled diabetes defined as a known diabetic with hemoglobin A1C (HBA1C) > 7.5 OR fasting glucose > 140
23. No uncontrolled hypertension defined as blood pressure (BP) > 140/90
24. No abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 28 days prior to registration

** Contact study team for complete eligibility details

Applicable Disease Sites
Brain and Nervous System

Participating Institutions
UF Gainesville : Sarah Andrews
UF Jacksonville : Sarah Andrews

Contact
Sarah Andrews, RN
Phone:

Email: Sarah.Andrews@neurosurgery.ufl.edu

More Information:
View study listing on ClinicialTrials.gov
http://www.clinicaltrials.gov/ct2/show/
NCT02523014