Dasatinib and Ipilimumab in Treating Patients With Gastrointestinal Stromal Tumors or Other Sarcomas That Cannot Be Removed by Surgery or Are Metastatic
This phase I trial studies the side effects and best dose of dasatinib when given together with ipilimumab in treating patients with gastrointestinal stromal tumors or other sarcomas that cannot be removed by surgery or have spread to other places in the body. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as ipilimumab, can block tumor growth in different ways by targeting certain cells. Giving dasatinib together with ipilimumab may work in treating patients with gastrointestinal stromal tumors or other sarcomas.
Gastrointestinal Stromal Tumor
Recurrent Adult Soft Tissue Sarcoma
Stage III Adult Soft Tissue Sarcoma
Stage IV Adult Soft Tissue Sarcoma
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of Dasatinib in Combination With Ipilimumab for Patients With Advanced Gastrointestinal Stromal Tumor and Other Sarcomas|
- Maximum tolerated dose defined as the highest dose studied for which the observed incidence of dose-limiting toxicity is less than 33% according to the National Cancer Institute Common Toxicity Criteria [ Time Frame: Up to week 12 ] [ Designated as safety issue: Yes ]Frequencies of toxicities will be tabulated.
- RR as measured by RECIST 1.1, Choi and immune-related response criteria [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]Immune related response rate (CR+PR) and Choi criteria will be calculated along with a 95% confidence interval.
- PFS as measured by RECIST 1.1, Choi and immune-related response criteria [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 3 years ] [ Designated as safety issue: No ]Will be estimated using Kaplan-Meier methodology.
- PFS at 6 months as measured by RECIST 1.1, Choi and immune-related response criteria [ Time Frame: 6 months ] [ Designated as safety issue: No ]Will be estimated using Kaplan-Meier methodology.
- OS [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]Will be estimated using Kaplan-Meier methodology.
- Humoral and cellular immune response [ Time Frame: Up to 4 weeks after treatment ] [ Designated as safety issue: No ]The relationship between clinical response, lymphocyte phenotype, and serum cytokines, and the effect of dasatinib in combination with ipilimumab on humoral and cellular immune responses will be evaluated.
- Change in tumor immunological markers in patients treated at the expansion cohort [ Time Frame: Baseline to up to week 6 ] [ Designated as safety issue: No ]Summary statistics for measures and changes from baseline of tumor-based markers including T-cell (cluster of differentiation [CD] 4, CD8, CD45, forkhead box P3), apoptosis markers, and indoleamine 2,3-dioxygenase 1/2 will be tabulated. Associations between biomarkers and efficacy measures will be analyzed in all response-evaluable subjects.
|Study Start Date:||July 2012|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (dasatinib and ipilimumab)
Patients receive dasatinib PO QD for 7 days. Patients then receive dasatinib PO QD and ipilimumab IV once on weeks 1, 4, 7 and 10. Beginning on week 24, patients then receive dasatinib PO QD and ipilimumab IV once every 12 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
Other Names:Biological: ipilimumab
Other Names:Other: laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studies
I. To assess the safety and tolerability of treatment with ipilimumab in combination with dasatinib in subjects with gastrointestinal stromal tumor (GIST) and other advanced sarcomas.
I. Response rate (RR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, immune-related response criteria, and Choi criteria.
II. Progression free survival (PFS). III. Progression-free survival at 6 months (PFS6months). IV. Overall survival (OS). V. Immunological correlative studies.
OUTLINE: This is a dose-escalation study of dasatinib.
Patients receive dasatinib orally (PO) once daily (QD) for 7 days. Patients then receive dasatinib PO QD and ipilimumab intravenously (IV) once on weeks 1, 4, 7 and 10. Beginning on week 24, patients then receive dasatinib PO QD and ipilimumab IV once every 12 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 4 weeks and then every 3 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01643278
|United States, New York|
|Memorial Sloan-Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Richard D. Carvajal 646-888-4161 email@example.com|
|Principal Investigator: Richard D. Carvajal|
|Principal Investigator:||Richard Carvajal||Memorial Sloan-Kettering Cancer Center|