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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief 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 Summary:

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.

Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

• Mean steady-state total (protein bound and non-protein bound) GDC-0449 plasma concentrations (Css) [ Time Frame: 21 days ]
  95% confidence interval estimates for 2 doses compared.
• Pharmacokinetics of GDC-0449, including the elimination rate constant and terminal half life [ Time Frame: Up to 3 months after completion of study treatment ]
  We will study two BSA defined strata.

Original Primary Outcome: Selection of an appropriate phase II dose based on observed toxicity and pharmacokinetic parameters

Current Secondary Outcome:

• Tumor responses [ Time Frame: Up to 30 days after completion of study treatment ]
  Descriptive statistics will be provided describing tumor responses.
• Progression-free survival [ Time Frame: Up to 30 days after completion of study treatment ]
  Kaplan-Meier estimates of the distribution of progression-free survival (PFS) will be constructed.

Original Secondary Outcome:

• Tumor response
• Progression-free survival

Information By: National Cancer Institute (NCI)

Dates:
Date Received: January 13, 2009
Date Started: January 2009
Date Completion:
Last Updated: April 1, 2014
Last Verified: June 2013