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

This phase II trial studies how well vismodegib and focal adhesion kinase (FAK) inhibitor GSK2256098 work in treating patients with meningiomas that may have gotten bigger or grew back after treatment. Vismodegib and FAK inhibitor GSK2256098 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Eligibility Criteria:

Documentation of Disease:
* Histologic Documentation: Histologically proven intracranial meningioma as documented by central pathology review.
* Molecular Documentation: Presence of SMO or NF2 mutation in tumor sample as documented by central laboratory (SMO W535L, SMO L412F or known missense COSMIC mutations, nonsense mutations, small indels or copy-number loss in NF2)
* Prior Treatment
- Prior 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 (XRT) to registration.
- Steroid dosing stable for at least 4 days.
* Not pregnant and not nursing.
* 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.
- Known active hepatitis B or C
- Current Child Pugh Class B or C liver disease
- Uncontrolled gastric ulcer disease (Grade 3 gastric ulcer disease within 28 days of registration)
- Uncontrolled diabetes defined as a known diabetic with hemoglobin A1C (HBA1C) > 7.5 OR fasting glucose > 140.
- Uncontrolled hypertension defined as blood pressure (BP) > 140/90
Abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 28 days prior to registration
Phase II
Alison Conlin, M.D.
Chris Fountain

The Pacific Cancer Research Consortium clinical trials are offered at multiple locations throughout Oregon, Washington, Alaska, California, and Idaho. To find a location near you, please contact the Patient Engagement Center at 844-552-2734.