Vismodegib in Treating Younger Patients With Recurrent or Refractory Medulloblastoma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01239316|
Recruitment Status : Completed
First Posted : November 11, 2010
Results First Posted : January 14, 2016
Last Update Posted : January 14, 2016
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Childhood Medulloblastoma||Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Vismodegib||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Clinical Trial Evaluating the Efficacy and Safety of GDC-0449 in Children With Recurrent or Refractory Medulloblastoma|
|Study Start Date :||November 2010|
|Actual Primary Completion Date :||June 2014|
|Actual Study Completion Date :||August 2015|
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: Laboratory Biomarker Analysis
Other: Pharmacological Study
- 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
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01239316
|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|
|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, 60611|
|United States, Maryland|
|National Cancer Institute Pediatric Oncology Branch|
|Bethesda, Maryland, United States, 20892|
|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 Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104|
|Children's Hospital of Pittsburgh of UPMC|
|Pittsburgh, Pennsylvania, United States, 15224|
|United States, Tennessee|
|St. Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38105|
|United States, Texas|
|Texas Children's Hospital|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Amar Gajjar||Pediatric Brain Tumor Consortium|