Dasatinib and Ipilimumab in Treating Patients With Gastrointestinal Stromal Tumors or Other Sarcomas That Cannot Be Removed by Surgery or Are Metastatic
|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: NCT01643278|
Recruitment Status : Completed
First Posted : July 18, 2012
Last Update Posted : January 10, 2017
|Condition or disease||Intervention/treatment||Phase|
|Gastrointestinal Stromal Tumor Stage III Soft Tissue Sarcoma Stage IV Soft Tissue Sarcoma||Drug: Dasatinib Biological: Ipilimumab Other: Laboratory Biomarker Analysis Other: Pharmacological Study||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||29 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of Dasatinib in Combination With Ipilimumab for Patients With Advanced Gastrointestinal Stromal Tumor and Other Sarcomas|
|Study Start Date :||July 2012|
|Actual Primary Completion Date :||June 2016|
|Actual Study Completion Date :||June 2016|
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: Laboratory Biomarker Analysis
Other: Pharmacological Study
- 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 ]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 ]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 ]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 ]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 ]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 ]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 ]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 ]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 ]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.
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): NCT01643278
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Sandra D'Angelo||Memorial Sloan Kettering Cancer Center|