tinzaparin in treating patients with metastatic kidney cancer that cannot be removed by surgery

Conditions: Kidney Cancer

Summary: 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.

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.

Eligibility criteria:
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

Keywords: clear cell renal cell carcinoma stage iv renal cell cancer recurrent renal cell cancer