Dasatinib and Ipilimumab in Treating Patients With Gastrointestinal Stromal Tumors or Other Sarcomas That Cannot Be Removed by Surgery or Are Metastatic
Gastrointestinal Stromal Tumor
Stage III Soft Tissue Sarcoma
Stage IV 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.
- OS as measured by RECIST 1.1, Choi and immune-related response criteria [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]Will be estimated using Kaplan-Meier methodology.
- 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.
- 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 (complete response + partial response) and Choi criteria will be calculated along with a 95% confidence interval.
- Change in humoral and cellular immune response [ Time Frame: Baseline to up to 4 weeks after treatment ] [ Designated as safety issue: No ]Relationships between clinical response, lymphocyte phenotype, cytokines, and effect of dasatinib and ipilimumab on humoral and cellular immune responses will be evaluated. Summary statistics for peripheral blood biomarkers of immunoregulatory activity (T-cell subpopulation counts, cytokines, and corresponding changes [or % changes]) will be tabulated by study day/dose. Time courses of biomarker measures will be investigated graphically; further analysis may be performed to characterize relationships. Associations between changes and dasatinib exposure will be explored graphically.
- Change in tumor immunological markers in patients treated at the expansion cohort (as of May 2015 patients on expansion cohort will not undergo protocol biopsies) [ 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.
- Downstream molecular effects of therapy on tumor viability as measured by changes in KIT expression and secondary mutations in resistant tumor specimens [ Time Frame: Baseline to up to 4 weeks after treatment ] [ Designated as safety issue: No ]Changes will be correlated with tumor response by Fisher's exact test.
- Genotype (v-Kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog [KIT] and platelet-derived growth factor receptor-alpha [PDGFR-a]) mutation status [ Time Frame: Baseline ] [ Designated as safety issue: No ]Associations of mutation status with response rate and PFS6months will be assessed using Fisher's exact test. Associations of mutation status with PFS and overall survival will be assessed using the log rank test.
|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
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: Sandra P. D'Angelo 646-888-4159 email@example.com|
|Principal Investigator: Sandra P. D'Angelo|
|Principal Investigator:||Sandra D'Angelo||Memorial Sloan Kettering Cancer Center|