NCT00822458

GDC-0449 in Treating Young Patients With Medulloblastoma That is Recurrent or Did Not Respond to Previous Treatment

A Phase I Pharmacokinetic and Safety Study in Children With Recurrent or Refractory Medulloblastoma to Identify a Pharmacokinetic Based Dose for GDC-0449

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 34 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 3 Years – 21 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial is studying the side effects and best dose of GDC-0449 in treating young patients with medulloblastoma that is recurrent or did not respond to previous treatment. GDC-0449 may be effective in treating young patients with medulloblastoma.

Detailed description

PRIMARY OBJECTIVE: I. To investigate the safety and pharmacokinetics of a daily dose of hedgehog antagonist GDC-0449 using the available formulation in pediatric patients with recurrent or refractory medulloblastoma. SECONDARY OBJECTIVES: I. To document and describe toxicities associated with this drug in these patients. II. To characterize the pharmacokinetics of this drug in these patients. III. To document preliminary antitumor activity of this drug in these patients. IV. To document pathologic and genomic methods to identify CNS tumors with activation of the PTCH/SHH pathway. OUTLINE: This is a multicenter study. Patients receive oral hedgehog antagonist GDC-0449 once daily on days 1 and 4-28 in course 1 and on days 1-28 in all subsequent courses. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity. Blood samples are collected periodically for pharmacokinetic studies. Archival tumor tissue samples are collected and analyzed for the expression of genes that activate the SHH (e.g., Gli1, Gli2, SFRP1, ATOH1, and PTCH2) or WNT (e.g., DKK2 and DKK4) cell signal pathways by in situ hybridization and reverse transcriptase real time-PCR. After completion of study therapy, patients are followed for 90 days.

Conditions

• Recurrent Childhood Medulloblastoma

Interventions

Type	Name	Description
DRUG	vismodegib	Given orally
OTHER	laboratory biomarker analysis
OTHER	pharmacological study

Timeline

• Start date: 2009-01-01
• Primary completion: 2013-09-01
• First posted: 2009-01-14
• Last updated: 2014-04-02

Locations

9 sites across 1 country: United States