07-742 Phase I/ Feasibility Study of Short Term Fondaparinux (Arixtra) in Chemotherapy-Pretreated Ovarian Carcinoma Patients at High Risk of Progression
A large body of work supports the association of abnormal coagulation (blood clot formation)
and malignancy. A coagulation enzyme thrombin is able to 1) enhance cancer cell adhesion to
platelets and endothelial cells 2) stimulate tumor cell growth, 3) increase metastasis and
4) stimulate tumor angiogenesis.
Thrombin inhibition has anti-metastatic and anti-tumor activity in mouse models. Recent
meta-analysis of 4 major randomized clinical trials that have evaluated the effect of
anticoagulants on overall survival in cancer patients comparing low molecular weight
heparin (LMWH) to placebo demonstrates a 13% risk reduction in mortality at 1 year and 10%
risk reduction at 2 years, which is statistically significant and independent of the
potential confounding effect of anticoagulation in the prevention of venous thromboembolic
Fondaparinux sodium (ARIXTRA® ) is a highly effective newer anticoagulant that is a fully
synthetic pentasaccharide. Arixtra binds to antithrombin III and subsequently inhibits
Factor Xa and hence thrombin generation. Arixtra has an excellent safety profile in clinical
trials of over 10,000 patients. When compared to LMWHs, ARIXTRA® has a potential
pharmacokinetic advantage based on its longer half-life of 16-17 hours.
The hypothesis to be tested is whether the completion of 8 weeks of ARIXTRA® in patients
with ovarian cancer who are in 'clinical remission' (no clinical evidence of disease) after
chemotherapy but at high risk of ovarian cancer recurrence is feasible and safe and if the
inhibition of thrombin generation by ARIXTRA® in ovarian cancer will result in decrease
ovarian cancer recurrence.
A concise description of the methodology:
The trial will be a prospective open-label cohort feasibility study of giving 2 months of
ARIXTRA® in patients at high risk of recurrence of ovarian cancer. The planned accrual is 15
patients. Patients will be treated with a fixed dose of ARIXTRA® 2.5 mg by subcutaneous
injection once daily. Treatment will continue for 2 months or until disease recurrence or
grade 3 adverse events or patient refusal.
In addition, all patients will be followed for survival and recurrence.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Estimate the proportion of patients who complete an eight week course of once daily administration of fondaparinux (Arixtra).
Boris Kobrinsky, M.D.
NYU School of Medicine
United States: Institutional Review Board
|NYU Cancer Institute Clinical Cancer Center||New York, New York 10016|