This phase II trial studies how well vismodegib works in treating patients with chondrosarcomas that have spread to other places in the body and usually cannot be cured or controlled with treatment. Drugs used in chemotherapy, such as vismodegib, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
PRIMARY OBJECTIVES: I. To 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). SECONDARY OBJECTIVES: 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. OUTLINE: Patients receive vismodegib orally (PO) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed up every 3 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
45
Institut Bergonie Cancer Center
Bordeaux, France
Centre Oscar Lambert
Lille, France
Centre Leon Berard
Lyon, France
Hopital De La Timone
Marseille, France
Institut Curie Paris
Paris, France
Gustave Roussy
Villejuif, France
Clinical Benefit Rate (CBR) Based on Centralized Imaging Review as Per RECIST 1.1
CBR was defined as the percentage of participants with complete or partial responses (CR, PR) or stable disease (SD) per RECIST 1.1. CR was defined as disappearance of all non-nodal target lesions. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Analysis of response was performed based on radiological centralized review. A 2-stage optimal Simon's design with 37 participants (first stage: 17 participants) was used. If 3 or less non-progressions (CR + PR + SD) at 6 months were observed during stage 1 (out of 17 participants), the trial would stopped early. Otherwise, 20 additional patients would be accrued for stage 2. If 11 or more non-progressions (out of 37 participants) were observed at the end of recruitment, further investigation of this therapy would be warranted.
Time frame: At 6 months after inclusion
Progression-free Survival
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.
Time frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 3 years
Overall Survival Per Response Evaluation Criteria in Solid Tumors Criteria 2009
Overall survival 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.
Time frame: Time from start of treatment to the time of death, assessed up to 3 years
Duration of Response
Will be described in responding subjects using descriptive statistics (median, extreme values, etc.).
Time frame: From the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 3 years
Mutational Status of Patched 1 and Smoothened
The 6-months clinical benefit rate will be correlated with the mutational status of patched and smoothened in order to identify predictive factors of clinical benefit from vismodegib.
Time frame: Baseline
Expression Pattern of Hedgehog Signaling Molecules by Using Quantitative Reverse Transcription-polymerase Chain Reaction and Immunohistochemistry
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 vismodegib.
Time frame: Baseline
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.