Vismodegib in Treating Patients With Advanced Chondrosarcomas
Other: Laboratory Biomarker Analysis
Other: Pharmacogenomic Study
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Study of GDC-0449 in Patients With Advanced Chondrosarcomas|
- Clinical benefit (complete response [CR] + partial response [PR] + stable disease [SD]) rate per RECIST criteria 2009 [ Time Frame: At 6 months ]At six months, patients will be classified as success (alive at 6 months AND CR/PR/ SD) or failure (dead OR alive with progression).
- Duration of response [ Time Frame: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 3 years ]Will be described in responding subjects using descriptive statistics (median, extreme values, etc.).
- Expression pattern of hedgehog signaling molecules by using quantitative reverse transcription-polymerase chain reaction and immunohistochemistry [ Time Frame: Baseline ]The 6-months clinical benefit rate will be correlated with the expression score of hedgehog signaling molecules in order to identify predictive factors of clinical benefit from GDC-0449.
- Mutational status of patched 1 (PTCH1) and smoothened SMO [ Time Frame: Baseline ]The 6-months clinical benefit rate will be correlated with the mutational status of PTCH and SMO in order to identify predictive factors of clinical benefit from GDC-0449.
- Overall survival (OS) per RECIST criteria 2009 [ Time Frame: Time from start of treatment to the time of death, assessed up to 3 years ]OS will be analyzed using the Kaplan-Meier method. The median survival rates will be reported with a 95% confidence interval. Median follow-up will be calculated using the reverse Kaplan-Meier method.
- Progression-free survival [ Time Frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 3 years ]Will be analyzed using the Kaplan-Meier method. The median survival rates will be reported with a 95% confidence interval. Median follow-up will be calculated using the reverse Kaplan-Meier method.
|Study Start Date:||December 2010|
|Primary Completion Date:||June 2016 (Final data collection date for primary outcome measure)|
Experimental: Treatment (vismodegib)
Patients receive vismodegib PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicities.
Other: Laboratory Biomarker Analysis
Correlative studiesOther: Pharmacogenomic Study
Other Name: PHARMACOGENOMICDrug: Vismodegib
I. Evaluate the antitumor activity of GDC-0449 (vismodegib) in terms of 6-month clinical benefit rate (complete response, partial response, and stable disease, as per the revised Response Evaluation Criteria in Solid Tumors [RECIST] criteria 2009).
I. Best overall response (as per the revised RECIST criteria 2009). II. 1- and 2-year progression-free survival. III. 1- and 2-year overall survival. IV. GDC-0449 safety. V. Pharmacogenomics analysis of predictive markers of treatment outcome.
Patients receive vismodegib orally (PO) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicities.
After completion of study therapy, patients are followed up every 3 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01267955
|Institut Bergonie Cancer Center|
|Bordeaux, France, 33076|
|Centre Oscar Lambert|
|Lille, France, 59020|
|Centre Leon Berard|
|Lyon, France, 69373|
|Hopital De La Timone|
|Marseille, France, 13385|
|Institut Curie Paris|
|Paris, France, 75005|
|Villejuif, France, 94805|
|Principal Investigator:||Antoine Italiano||Institut Bergonie Cancer Center|