Tinzaparin in Treating Patients With Metastatic Kidney Cancer That Cannot Be Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: Tinzaparin may stop the growth of kidney cancer by blocking blood flow to the tumor. PURPOSE: This phase I/II trial is studying the side effects of tinzaparin and to see how well it works in treating patients with metastatic kidney cancer that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Primary Determine the effect of tinzaparin sodium on fibrin formation (prothrombin fragment F1.2), thrombin generation (thrombin-antithrombin complexes), and fibrinolysis (D-Dimer) from baseline to 2 weeks and at nadir or disease progression in patients with unresectable metastatic renal cell carcinoma (RCC). Secondary Determine the effect of tinzaparin sodium treatment on circulating angiogenesis markers, including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Determine the proportion of patients developing venous thromboembolism and hemorrhage. Determine the tolerability of tinzaparin sodium treatment for up to 6 months in these patients. Establish the feasibility of undertaking a multicenter renal cell carcinoma trial with specialized coagulation test collection, shipping, and processing. Obtain more accurate and specific mean, median, and variability in biomarker data in advanced RCC patients treated with tinzaparin sodium for purposes of planning larger future trials. Estimate the progression-free survival at 4 months in patients treated with tinzaparin sodium. Correlate progression-free survival with changes in markers of coagulation activation or angiogenesis. Correlate the anticoagulant activity of tinzaparin sodium (anti-Xa activity) with change in coagulation markers, angiogenesis markers, and progression-free survival. OUTLINE: This is an open-label, pilot, multicenter study. Patients receive a treatment dose of tinzaparin sodium subcutaneously (SC) once daily for 14 days followed by a prophylactic dose of tinzaparin sodium SC once daily for up to 6 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

Official Title
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A Phase I/II Trial of Tinzaparin (Innohep), a Low Molecular Weight Heparin (LMWH) for Treatment of Advanced Renal Cell Carcinoma

Conditions
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Kidney Cancer

Intervention / Treatment
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* Drug: tinzaparin sodium


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed renal cell carcinoma of clear cell histology Tumors of mixed histology eligible if ≥ 50% of tumor has clear cell histology No nonclear cell histologies, collecting duct tumors, oncocytomas, or transitional cell tumors Metastatic and unresectable disease that is clinically extending beyond the regional lymph nodes (histological confirmation not required) Patients who are inoperable for their primary tumor representing the sole site of disease are ineligible Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 2 cm by conventional techniques OR ≥ 1 cm by spiral CT scan No known brain metastases PATIENT CHARACTERISTICS: Expected survival > 2 months CALGB (ECOG/ZUBROD) performance status (PS) 0-2 OR Karnofsky PS 60-100% Hemoglobin ≥ 10 g/dL Platelet count ≥ 100,000/mm^3 Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST/ALT ≤ 1.5 times ULN Creatinine ≤ 1.5 times ULN INR ≤ 1.5 times control value PTT < 1.5 times control value Negative pregnancy test Fertile patients must use effective contraception Patients must be able to receive subcutaneous injections at home No other primary malignancy in the past 5 years other than basal cell carcinoma or carcinoma in situ of the cervix that has been curatively treated and is associated with a less than 30% risk of relapse in the next 5 years No signs or symptoms of bleeding within 4 the past weeks No known bleeding diathesis or high risk for bleeding due to any condition, including trauma within the past 4 weeks, active current bleeding, or hemorrhagic stroke or intraocular bleeding within the past 6 months No active thromboembolism highly likely to require anticoagulation during the study period No known or suspected history of type II heparin-induced thrombocytopenia No allergy or hypersensitivity to heparin, tinzaparin sodium, pork products, sulfite, or benzyl alcohol No uncontrolled severe intercurrent illness, including ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements No uncontrolled arterial hypertension, history of gastrointestinal ulceration, and/or bleeding in the past 4 weeks No diabetic retinopathy or history of retinal hemorrhage Not pregnant or nursing HIV-positive patients are allowed PRIOR CONCURRENT THERAPY: No treatment with anticoagulation lasting > 1 month in the past 6 months No anticoagulation, including treatment with a low molecular weight heparin, at any time within the past month More than 4 weeks since prior surgery, radiation therapy, immunotherapy, or chemotherapy Recovered from prior therapy No other concurrent investigational agents No other concurrent anticoagulation therapy, including oral anticoagulants, thrombolytic agents, or any form of heparin Concurrent antiplatelet agents allowed No spinal or epidural puncture, anesthesia, or post-operative indwelling epidural catheters within the past 48 hours No other concurrent anticancer agents or therapies No concurrent sex hormones except for postmenopausal hormone replacement No concurrent chemotherapy or immunotherapy No concurrent palliative radiotherapy Concurrent urgent use of corticosteroids allowed

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: tinzaparin sodium|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood markers or coagulation as measured by plasma prothrombin F1.2, thrombin-antithrombin complexes, and D-dimers at 2 weeks, 2 months and 6 months |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood markers of angiogenesis as measured by serum vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) at 2 weeks, 2 months, and 6 months |  |  | 
| Venous thromboembolism as measured by clinical evaluation at 6 months |  |  | 
| Progression free survival as measured by clinical evaluation at 4 months |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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clear cell renal cell carcinoma, stage IV renal cell cancer, recurrent renal cell cancer