Phase I Study of Dasatinib in Combination With Ipilimumab for Patients With Advanced Gastrointestinal Stromal Tumor and Other Sarcomas
Overview
- Phase
- Phase 1
- Intervention
- Dasatinib
- Conditions
- Gastrointestinal Stromal Tumor
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 29
- Locations
- 1
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •DOSE ESCALATION COHORT: subjects must have histologically or cytologically confirmed sarcoma that is metastatic or unresectable
- •DOSE EXPANSION COHORT: subjects must have histologically or cytologically confirmed GIST that is metastatic or unresectable
- •Patients must have measurable disease per RECIST 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
- •DOSE ESCALATION COHORT: patients must have had at least one prior therapy
- •DOSE EXPANSION COHORT: GIST patients must have had progression on or have been intolerant to imatinib and sunitinib
- •Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
- •Life expectancy of greater than 3 months
- •Leukocytes \>= 3 K/mcL
- •Absolute neutrophil count \>= 1.5 K/mcL
- •Platelets \>= 100 K/mcL
Exclusion Criteria
- •Patients who have had chemotherapy (non-tyrosine kinase inhibitor \[TKI\]) or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- •Patients with a history of prior treatment with ipilimumab or dasatinib
- •Patients who are receiving any other investigational agents
- •Patients with known brain metastases are excluded from this clinical trial
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to dasatinib and ipilimumab
- •Patients who require concurrent treatment with any medications or substances that are potent inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)
- •Patients who require concurrent treatment with any medications or substances that have significant proarrhythmic potential are ineligible
- •Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain dasatinib tablets are excluded
- •Patients may not have any clinically significant cardiovascular disease including the following:
- •Myocardial infarction or ventricular tachyarrhythmia within 6 months
Arms & Interventions
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.
Intervention: Dasatinib
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.
Intervention: Ipilimumab
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.
Intervention: Laboratory Biomarker Analysis
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.
Intervention: Pharmacological Study
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- OS as measured by RECIST 1.1, Choi and immune-related response criteria(Up to 3 years)
- PFS as measured by RECIST 1.1, Choi and immune-related response criteria(From start of treatment to time of progression or death, whichever occurs first, assessed up to 3 years)
- PFS at 6 months as measured by RECIST 1.1, Choi and immune-related response criteria(6 months)
- RR as measured by RECIST 1.1, Choi and immune-related response criteria(Up to 3 years)