Clinical Trial: Vismodegib in Treating Younger Patients With Recurrent or Refractory Medulloblastoma

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

Official Title: A Phase II Clinical Trial Evaluating the Efficacy and Safety of GDC-0449 in Children With Recurrent or Refractory Medulloblastoma

Brief Summary: This phase II trial studies how well vismodegib works in treating younger patients with recurrent or refractory medulloblastoma. Vismodegib may slow the growth of tumor cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Estimate the efficacy of GDC-0449 (vismodegib) treatment for pediatric patients with recurrent or refractory medulloblastoma, as measured by the sustained objective response rates for patients without (stratum A) and with (stratum B) evidence of activation of Hedgehog (Hh) signaling pathway in their tumors.

II. Characterize the pharmacokinetics (plasma) of GDC-0449 in children/adolescents with refractory medulloblastoma.

III. To document pathologic and genomic methods to identify medulloblastomas with activation of the Hh signaling pathway.

SECONDARY OBJECTIVES:

I. Document and describe toxicities associated with GDC-0449 administered on a daily schedule.

II. Estimate the duration of objective response and progression-free survival (PFS).

III. Characterize the pharmacokinetics (cerebrospinal fluid) of GDC-0449 in children/adolescents with refractory medulloblastoma.

OUTLINE: This is a multicenter study. Patients are stratified according to evidence of activation of Hedgehog signaling pathway in their tumors (without vs with vs unknown).

Patients receive vismodegib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.

Plasma and cerebrospinal fluid samples are collected periodically for pharmacokinetic and other correlative studies.

After completion of stud
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

• Objective Response (CR+PR) Sustained for ≥ 8 Weeks [ Time Frame: Up to 12 months ]
  Objective response is either a complete response or a partial response sustained for 8 weeks in a patient. The objective response rate will be reported separately for patients of each stratum. CR is complete disappearance of all enhancing tumor. PR is >= 50% reduction in tumor size.
• Pharmacokinetics (Plasma) of GDC-0449 [ Time Frame: up to 12 month ]
  plasma GDC-0449 concentration of day 21 in first course

Original Primary Outcome: Objective response rates (partial and complete response) for patients without and with evidence of activation of Hedgehog signaling pathway in their tumors

Current Secondary Outcome:

• Progression-free Survival [ Time Frame: From start of treatment up to 2 years ]
  Progression-free survival (PFS) is measured from the date of initial treatment with GDC-0449 until the earliest of progression or death on study. PFS is censored at the last tumor assessment date for patients without disease progression who have not died within 30 days of last exposure to study treatment. Kaplan-Meier method is used to estimate the progression-free survival.
• Duration of Objective Response [ Time Frame: From start of treatment up to 2 years ]
  The duration of objective response is measured from the initial scan documenting complete or partial response that was subsequently confirmed until the earlier of documented progression or death on study. Duration of objective response is censored at the last tumor assessment date for patients without disease progression who have not died within 30 days of last exposure to study treatment.
• Pharmacokinetic Parameters of Vismodegib, CSF Penetration [ Time Frame: up to 12 month ]
  The estimated median of cerebrospinal fluid (CSF) drug penetration is reported when expressed as an AUC ratio of CSF vismodegib to that of unbound drug in plasma.

Original Secondary Outcome:

• Duration of sustained objective response
• Duration of progression-free survival

Information By: National Cancer Institute (NCI)

Dates:
Date Received: November 10, 2010
Date Started: November 2010
Date Completion:
Last Updated: December 10, 2015
Last Verified: April 2015