A071401 Meningioma

• Documentation of disease:
  • Histologic documentation: histologically proven intracranial meningioma as documented by central pathology review
  • Molecular documentation: presence of SMO, PTCH1 or NF2 mutation in tumor sample as documented by central laboratory
  • 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

• 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
• Prior treatment
  • Prior medical 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 to registration
  • Steroid dosing stable for at least 4 days
  • Recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or less toxicity from other agents with exception of alopecia and fatigue
  • No craniotomy within 28 days of registration

• 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)

• 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
  • No known active hepatitis B or C
  • No current Child Pugh class B or C liver disease
  • No uncontrolled gastric ulcer disease (grade 3 gastric ulcer disease within 28 days of registration)
  • No uncontrolled diabetes defined as a known diabetic with hemoglobin A1C (HBA1C) > 7.5 OR fasting glucose > 140
  • No uncontrolled hypertension defined as blood pressure (BP) > 140/90
  • No abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 28 days prior to registration

• Concomitant medications:
  • Chronic concomitant treatment with strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors must discontinue the drug for 14 days prior to registration on the study for patients with NF2 mutation enrolled to GSK2256098
  • Chronic concomitant treatment with strong CYP3A4 inducers is not allowed; patients must discontinue the drug 14 days prior to the start of study treatment for patients with NF2 mutation enrolled to GSK2256098

• Absolute neutrophil count (ANC) >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• Creatinine OR =< 1.5 mg/dl x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance > 45 mL/min
• Urine protein:creatinine ratio (UPC) =< 45 mg/mmol; ONLY APPLICABLE for patients with NF2 mutation (GSK2256098)
• Total bilirubin =< 1.5 x upper limit of normal (ULN); except in case of Gilbert's disease
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
• Fasting triglyceride =< 200 mg/dL; ONLY APPLICABLE for patients with NF2 mutation (GSK2256098)
• Fasting cholesterol =< 240 mg/dL; ONLY APPLICABLE for patients with NF2 mutation (GSK2256098)
• Corrected QC interval calculated using Fridericia's formula (QTcF) =< 500 msec; ONLY APPLICABLE for patients with NF2 mutation (GSK2256098)