This phase I trial studies the side effects and best dose of dalteparin when given together with sunitinib malate in treating patients with kidney cancer that has spread to other parts of the body or cannot be removed by surgery. Anticoagulants, such as dalteparin, help prevent blood clots and have been shown to increase survival in patients with cancer. Anticoagulants may also prevent the formation of new blood vessels. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by inhibiting new blood vessels and blocking blood flow to the tumor. Giving dalteparin together with sunitinib malate may starve tumors and kill more tumor cells.
PRIMARY OBJECTIVES: I. To determine the recommended dosing for the combination of sunitinib (sunitinib malate) and dalteparin in patients with metastatic renal cell carcinoma. II. To evaluate safety and tolerability for the combination of sunitinib and dalteparin in patients with metastatic renal cell carcinoma. III. To determine early signs of clinical activity of the combination of sunitinib and dalteparin in patients with metastatic renal cell carcinoma. SECONDARY OBJECTIVES: I. To determine the clinical response rate of sunitinib and dalteparin in patients with metastatic renal cell carcinoma. II. To determine time-to-progression (TTP) and overall survival amongst patients with metastatic renal cell carcinoma receiving sunitinib and dalteparin. III. To determine the effect of sunitinib alone and dalteparin alone compared to the combination of dalteparin plus sunitinib on plasma coagulation parameters. IV. To determine the effect of sunitinib alone and dalteparin alone compared to the combination of dalteparin plus sunitinib on angiogenesis parameters in blood. OUTLINE: This is a dose-escalation study of dalteparin. Patients receive sunitinib malate orally (PO) once daily (QD) in weeks 1-4 and dalteparin subcutaneously (SC) QD in week 6 during course 1. In all subsequent courses, patients receive sunitinib malate PO QD in weeks 1-4 and dalteparin SC QD in weeks 1-6. Courses repeat every 6 weeks 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 for 3 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
16
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Academ Zienkenhuis Bij De University
Amsterdam, Netherlands
VU University Medical Center
Amsterdam, Netherlands
Early signs of clinical activity of the combination of sunitinib malate and dalteparin
Time frame: Up to 4 years
Incidence of toxicities for the combination of dalteparin and sunitinib malate
Toxicities will be summarized by tabulation. Summaries will be made across all types of toxicities and by grade and type.
Time frame: Up to 4 weeks after last treatment
Recommended dosing for the combination of dalteparin and sunitinib malate
The maximally tolerated dose (MTD) will be the highest dose at which \< 33% of patients (=\< 2 out of 6 patients) suffer from dose limiting toxicities (DLTs) related to the combination treatment.
Time frame: Up to 4 weeks
Clinical response rate of dalteparin and sunitinib malate, determined as the proportion of treated patients who had partial or complete response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0
Time frame: Up to 4 weeks after last treatment
Overall survival
Described in all patients using Kaplan-Meier curves.
Time frame: Up to 4 years
TTP
Described in all patients using Kaplan-Meier curves.
Time frame: Up to 4 years
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