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

Inclusion 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