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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

Phase 1/Phase 2
18 Years
Open (Enrolling)
Kidney Cancer

Thank you

Trial Information

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



- 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).


- 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

- 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

- 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.

Inclusion Criteria


- Histologically or cytologically confirmed renal cell carcinoma of clear cell

- 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


- 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

- 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

- 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


- 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

- 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

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Safety Issue:


Principal Investigator

Deborah L. Ornstein, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Yale University


United States: Food and Drug Administration

Study ID:




Start Date:

December 2005

Completion Date:

Related Keywords:

  • Kidney Cancer
  • clear cell renal cell carcinoma
  • stage IV renal cell cancer
  • recurrent renal cell cancer
  • Carcinoma, Renal Cell
  • Kidney Neoplasms



University of Chicago Cancer Research Center Chicago, Illinois  60637
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center Lebanon, New Hampshire  03756-0002
Vermont Cancer Center at University of Vermont Burlington, Vermont  05405-0075