Clinical Trial: Vismodegib in Treating 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 Adults With Recurrent or Refractory Medulloblastoma

Brief Summary: This phase II trial is studying how well vismodegib works in treating adult patients with recurrent or refractory medulloblastoma. Vismodegib may slow the growth of tumor cells and may be an effective treatment for medulloblastoma.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To estimate the efficacy of GDC-0449 (vismodegib) treatment for adult patients with recurrent or refractory medulloblastoma, as measured by the objective response rates for patients without (Stratum A) and with (Stratum B) evidence of activation of Sonic Hedgehog (SHH) signaling pathway tumors.

SECONDARY OBJECTIVES:

I. To assess the safety and tolerability of GDC-0449 administered on a once daily schedule.

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

III. To characterize the pharmacokinetics (plasma and cerebrospinal fluid) of GDC-0449 in adults with refractory medulloblastoma.

IV. To document pathologic and genomic methods to identify CNS tumors with activation of the PTCH/SHH pathway.

V. To describe the objective responses observed in patients whose pathologic assessment of tumor result in unknown (Stratum C) evidence of activation of Sonic Hedgehog (SHH) signaling pathway tumors.

OUTLINE: This is a multicenter study. Patients are stratified according to PTCH/Sonic Hedgehog signaling pathway activation (inactivated vs activated vs unknown).

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

After completion of study treatment, patients are followed up periodically for up to 12 months.

Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Objective Response (CR+PR) Sustained for ≥ 8 Weeks [ Time Frame: Up to 12 months ]

Original Primary Outcome: Objective response rate

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:

• Safety and tolerability
• Duration of objective response and progression-free survival
• Pharmacokinetics
• Identification of CNS tumors with activation of the PTCH/Sonic Hedgehog pathway using pathologic and genomic methods

Information By: National Cancer Institute (NCI)

Dates:
Date Received: July 14, 2009
Date Started: June 2009
Date Completion:
Last Updated: January 28, 2016
Last Verified: March 2015