Vismodegib in Treating Patients With Recurrent or Refractory Medulloblastoma
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.
Other: pharmacological study
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Clinical Trial Evaluating the Efficacy and Safety of GDC-0449 in Adults With Recurrent or Refractory Medulloblastoma|
- Objective response rates (PR and CR) graded using RECIST criteria [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]Ninety-five percent confidence interval estimates of the true, unknown objective response rate will be constructed for each of the three strata. The proportions of patients with confirmed complete responses, partial responses and stable disease will be reported descriptively for each of the three strata. Cumulative incidence functions of time to objective response will also be provided.
- Duration of sustained objective response [ Time Frame: From the initial scan documenting complete or partial response that was subsequently confirmed until the earlier of documented progression or death on study, assessed up to 12 months ] [ Designated as safety issue: No ]Kaplan-Meier estimates will be constructed.
- Progression-free survival [ Time Frame: From the date of initial treatment with GDC-0449 until the earliest of progression or death on study, assessed up to 12 months ] [ Designated as safety issue: No ]Kaplan-Meier estimates will be constructed.
- Pharmacokinetic parameters of vismodegib, estimated using compartmental methods [ Time Frame: Up 12 months ] [ Designated as safety issue: No ]Plasma and cerebrospinal fluid (CSF) drug concentrations and pharmacokinetic parameters will be presented in tabular and graphical form.
|Study Start Date:||June 2009|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (vismodegib)
Patients receive vismodegib 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.
Other Names:Other: pharmacological study
Other Name: pharmacological studies
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.
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.
|United States, California|
|Children's Hospital Los Angeles|
|Los Angeles, California, United States, 90027|
|Lucile Packard Children's Hospital Stanford University|
|Palo Alto, California, United States, 94304|
|University of California at San Francisco - Comprehensive Cancer Center|
|San Francisco, California, United States, 94143-0875|
|United States, District of Columbia|
|Children's National Medical Center|
|Washington, District of Columbia, United States, 20010|
|United States, Illinois|
|Lurie Children's Hospital-Chicago|
|Chicago, Illinois, United States, 60614|
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229|
|United States, Pennsylvania|
|Children's Hospital of Pittsburgh of UPMC|
|Pittsburgh, Pennsylvania, United States, 15224|
|United States, Tennessee|
|Pediatric Brain Tumor Consortium|
|Memphis, Tennessee, United States, 38105|
|St. Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38105|
|United States, Texas|
|Baylor College of Medicine|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Amar Gajjar||Pediatric Brain Tumor Consortium|