Vismodegib in Treating Younger Patients With Recurrent or Refractory Medulloblastoma
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.
Recurrent Childhood Medulloblastoma
Other: pharmacological study
Other: laboratory biomarker analysis
|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 Children With Recurrent or Refractory Medulloblastoma|
- Objective response rates (partial and complete response) [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]Simon two-staged MinMax designs will be used to assess the rates of best objective response prior to progression.
- 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. 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 progression-free survival [ Time Frame: From the date of initial treatment 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.
|Study Start Date:||November 2010|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (vismodegib)
Patients receive vismodegib PO QD 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 studiesOther: laboratory biomarker analysis
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.
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 study treatment, patients are followed up every other month for up to 12 months.
|United States, California|
|Children's Hospital Los Angeles||Recruiting|
|Los Angeles, California, United States, 90027|
|Contact: Girish Dhall 323-361-4629 firstname.lastname@example.org|
|Principal Investigator: Girish Dhall|
|Lucile Packard Children's Hospital Stanford University||Recruiting|
|Palo Alto, California, United States, 94304|
|Contact: Paul G. Fisher 650-721-5889 email@example.com|
|Principal Investigator: Paul G. Fisher|
|United States, District of Columbia|
|Children's National Medical Center||Recruiting|
|Washington, District of Columbia, United States, 20010|
|Contact: Roger J. Packer 202-884-2120 firstname.lastname@example.org|
|Principal Investigator: Roger J. Packer|
|United States, Illinois|
|Lurie Children's Hospital-Chicago||Recruiting|
|Chicago, Illinois, United States, 60614|
|Contact: Stewart Goldman 312-227-4844 email@example.com|
|Principal Investigator: Stewart Goldman|
|United States, Maryland|
|National Cancer Institute Pediatric Oncology Branch||Not yet recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: Katherine E. Warren 301-435-4683 firstname.lastname@example.org|
|Principal Investigator: Katherine E. Warren|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Ira J. Dunkel 212-639-2153 email@example.com|
|Principal Investigator: Ira J. Dunkel|
|United States, North Carolina|
|Duke University Medical Center||Recruiting|
|Durham, North Carolina, United States, 27710|
|Contact: Sridharan Gururangan 919-684-3506 firstname.lastname@example.org|
|Principal Investigator: Sridharan Gururangan|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center||Recruiting|
|Cincinnati, Ohio, United States, 45229|
|Contact: Maryam Fouladi 513-803-0721 email@example.com|
|Principal Investigator: Maryam Fouladi|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Peter C. Phillips 215-590-2107 firstname.lastname@example.org|
|Principal Investigator: Peter C. Phillips|
|Children's Hospital of Pittsburgh of UPMC||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15224|
|Contact: Ian F. Pollack 412-692-5881 email@example.com|
|Principal Investigator: Ian F. Pollack|
|United States, Tennessee|
|St. Jude Children's Research Hospital||Recruiting|
|Memphis, Tennessee, United States, 38105|
|Contact: Amar Gajjar 901-595-4599 firstname.lastname@example.org|
|Principal Investigator: Amar Gajjar|
|United States, Texas|
|Texas Children's Hospital||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Murali M. Chintagumpala 832-822-4266 email@example.com|
|Principal Investigator: Murali M. Chintagumpala|
|Principal Investigator:||Amar Gajjar||Pediatric Brain Tumor Consortium|