Neoplasms

All Conditions

Digestive System Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Sarcoma

Gastrointestinal Stromal Tumors

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Connective Tissue

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Soft Tissue Sarcoma

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Antibodies

Antibodies, Monoclonal

Ipilimumab

Immunoglobulins

Dasatinib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

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.

Laboratory Biomarker Analysis

Pharmacological Study

Sandra D'Angelo

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 be a better treatment for patients with gastrointestinal stromal tumors or other sarcomas.

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

Dasatinib and Ipilimumab in Treating Patients With Gastrointestinal Stromal Tumors or Other Sarcomas That Cannot Be Removed by Surgery or Are Metastatic

Phase I Study of Dasatinib in Combination With Ipilimumab for Patients With Advanced Gastrointestinal Stromal Tumor and Other Sarcomas

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.

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.

Changes will be correlated with tumor response by Fisher's exact test.

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.

Frequencies of toxicities will be tabulated.

Will be estimated using Kaplan-Meier methodology.

Immune related response rate (complete response + partial response) and Choi criteria will be calculated along with a 95% confidence interval.

Spots Global Cancer Trial Database for stage iv soft tissue sarcoma