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
- Estimate the progression-free survival at 4 months in patients treated with tinzaparin
- Correlate progression-free survival with changes in markers of coagulation activation
- 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.
Masking: Open Label, Primary Purpose: Treatment
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
Deborah L. Ornstein, MD
United States: Food and Drug Administration
|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|