GDC-0449 in Treating Patients With Recurrent Glioblastoma Multiforme That Can Be Removed by Surgery

Inclusion Criteria

• Patients must have histologically proven glioblastoma which is progressive or recurrent following radiation therapy +/- chemotherapy
• Patients must have measurable contrast-enhancing progressive or recurrent glioblastoma by MRI imaging prior to starting treatment; patient must be able to tolerate MRIs
• Patients must be eligible for surgical resection according to the following criteria:
• Patient competent to sign consent
• Expectation that the surgeon can resect >= 50% of the Gd-enhancing tumor with low risk of inducing neurological injury
• Lack of hematologic, cardiac or other medical contraindications to surgery
• Surgery must take place Monday-Thursday, with the exception of patients being treated at Cleveland Clinic/University Hospitals: these patients may undergo surgery Monday-Friday
• Patients must have a tumor size ≥ 2.5 cm in diameter in two perpendicular planes in order to enable correlative studies
• Paraffin embedded tissue must be available from initial surgical resection at diagnosis (prior to any treatment)
• Patients may have an unlimited number of prior therapy regimens
• Patients must have recovered from severe toxicity of prior therapy; the following intervals from previous treatments are required to be eligible:
• 3 months from the completion of radiation
• 6 weeks from a nitrosourea chemotherapy
• 3 weeks from a non-nitrosourea chemotherapy
• 4 weeks from any investigational (not FDA-approved) agents
• 2 weeks from administration of a non-cytotoxic, FDA-approved agent (e.g., tarceva, hydroxychloroquine, bevacizumab, etc.)
• Patients may be on a non-enzyme-inducing anti-epileptic drug (non-EIAED); they may not be on an EIAED; if previously on an EIAED, patient must be off for at least 14 days prior to the first dose of GDC-0449
• Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
• White blood cells (WBC) ≥ 3,000/mcL
• Absolute neutrophil count ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Total bilirubin ≤ institutional upper limit of normal
• Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) ≤ 4.0 X institutional upper limit of normal
• Creatinine within institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Patients must be able to provide written informed consent
• The effects of GDC-0449 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because Hh signal pathway inhibitors are known to be teratogenic, women of child-bearing potential and men must use two forms of contraception (i.e., barrier contraception and one other method of contraception) prior to study entry, for the duration of study participation, and for at least 12 months post-treatment; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Women of childbearing potential are required to have a negative serum pregnancy test (with a sensitivity of at least 25 milli 0international unit/microliter (mL) within 10-14 days prior to treatment start and be required to agree to have the test repeated within 24 hours prior to the first dose of GDC-0449 (serum or urine); a pregnancy test (serum or urine) will be administered every 4 weeks if their menstrual cycles are regular or every 2 weeks if their cycles are irregular while on study within the 24-hour period prior to the administration of GDC-0449; a positive urine test must be confirmed by a serum pregnancy test; prior to dispensing GDC-0449, the investigator must confirm and document the patient's use of two contraceptive methods, dates of negative pregnancy test, and confirm the patient's understanding of the teratogenic potential of GDC-0449; women of childbearing potential are defined as follows:
• Patients with regular menses

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