Clinical Trial 18660

Cancer Type: Neurologic Oncology
Interventions:GSK2256098; Vismodegib (Erivedge)

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Peter Forsyth

Overview

Study Title

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

Summary

The purpose of this study is to test good and bad effects of these two different study drugs against meningioma tumors with altered genes. 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.

Objective

2.0 OBJECTIVES 2.1 Primary objectives: 2.1.1 To determine the activity of a SMO inhibitor in patients with meningiomas harboring SMO mutations as measured by 6-month PFS and response rate. 2.1.2 To determine the activity of a FAK inhibitor in patients with meningiomas harboring NF2 mutations as measured by 6-month PFS and response rate. 2.2 Secondary objectives: 2.2.1 To determine overall survival and progression-free survival of SMO and FAK inhibitors in patients with meningioma. 2.2.2 To determine adverse event rates of SMO and FAK inhibitors in patients with meningioma. 2.3 Correlative science objectives: 2.3.1 To evaluate genetic biomarkers in meningioma. 2.3.2 To evaluate dynamic contrast enhanced MRI during treatment with SMO and FAK inhibitors for meningioma.

Inclusion Criteria

  • Central Pathology Review Submission: Must have local diagnosis of meningioma (any grade) and have formalin fixed paraffin embedded (FFPE) tumor block OR meningioma tissue slides available for submission to central pathology review and SMO and NF2 testing by a CLIA-certified lab.
  • Documentation of Disease: a) Histologic Documentation: Histologically proven intracranial meningioma as documented by central pathology review. b) 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).
  • Progressive OR residual disease: a) 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. will be defined by bidimensionally measurable lesions with clearly defined margins by MRI scans, with a minimum diameter of 10 mm in both dimensions. b) 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. c) 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 is defined by a bidimensionally measurable main lesion on magnetic resonance imaging (MRI) or computed tomography (CT) images with clearly defined margins. Multifocal disease is allowed.
  • Prior Treatment: a) Prior therapy is allowed but not required. b) No limit on number of prior therapies. c) No chemotherapy, other investigational agents within 28 days of study treatment. d) No other concurrent investigational agents or other meningioma-directed therapy while on study. d) 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. e) Steroid dosing stable for at least 4 days. f) Recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or less toxicity from other agents with exception of alopecia and fatigue. g) No craniotomy within 28 days of registration.
  • Not pregnant and not nursing.
  • Age ≥ 18 years.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
  • History: a) 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. b) No metastatic meningiomas) allowed. c) No history of allergic reactions attributed to compounds of similar or biologic composition to assigned study drug. d) No known active hepatitis B or C. e) No current Child Pugh Class B or C liver disease. f) No uncontrolled gastric ulcer disease. g) No uncontrolled diabetes. h) No uncontrolled hypertension. i) No abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 28 days prior to registration.
  • Concomitant Medications: a) Chronic concomitant treatment with strong inhibitors of CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration (patients with NF2 mutation enrolled to GSK2256098). b) Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Must discontinue the drug 14 days prior to the start of study treatment for participants with NF2 mutation enrolled to GSK2256098.
  • Must meet required initial laboratory values.

  • Exclusion Criteria

  • Does not meet Inclusion Criteria listed