Conditions: Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Recurrent Adult Brain Tumor
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 44
Healthy volunteers: no

Brief summary:
This randomized phase II trial is studying how well GDC-0449 works in treating patients with recurrent glioblastoma multiforme that can be removed by surgery. GDC-0449 may be effective in treating patients with glioblastoma multiforme.

Detailed description:
PRIMARY OBJECTIVES:

I. 6-month progression-free survival (PFS-6) measured from start of treatment following surgery.

SECONDARY OBJECTIVES:

I. Toxicity. (Clinical) II. Overall survival. (Clinical) III. Tumor response. Partial Response (PR) + Complete Response (CR): MacDonald criteria). (Clinical)

Correlative Studies

* Determination of in vivo drug effect in recurrent Glioblastoma Multiform (GBM). (Correlative studies)
* Determination of in vitro drug effect on CD133+ glioma-derived neurospheres. (Correlative studies)
* Determination of Sonic Hedgehog pathway activation in primary vs. recurrent GBM. (Correlative studies)

TERTIARY OBJECTIVES:

I. Correlate clinical outcome (6 mo PFS) with biologic correlates (1-3) above.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral Hedgehog antagonist GDC-0449 once daily for 7 days before surgery.

Arm II: Patients do not receive treatment before surgery. Beginning within 28 days after surgical resection, all patients receive oral Hedgehog antagonist GDC-0449 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Fresh and paraffin-embedded tissue samples are collected for correlative laboratory studies.

After completion of study treatment, patients are followed up every 2 months.

Arms:
arm 1: Patients receive oral Hedgehog antagonist GDC-0449 (vismodegib) once daily for 7 days before therapeutic conventional surgery. Beginning within 28 days after surgical resection, all patients receive oral Hedgehog antagonist GDC-0449 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: pharmacological study; laboratory biomarker analysis arm 2: Patients do not receive treatment before therapeutic conventional surgery.

Beginning within 28 days after surgical resection, all patients receive oral Hedgehog antagonist GDC-0449 (vismodegib) once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: laboratory biomarker analysis

Interventions: intervention 1: vismodegib intervention 2: therapeutic conventional surgery intervention 3: laboratory biomarker analysis intervention 4: pharmacological study
Intervention descriptions: intervention 1: Given orally intervention 2: undergo surgery intervention 3: correlative studies intervention 4: correlative studies

Protocol document: