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07-742 Phase I/ Feasibility Study of Short Term Fondaparinux (Arixtra) in Chemotherapy-Pretreated Ovarian Carcinoma Patients at High Risk of Progression

Phase 1
18 Years
75 Years
Not Enrolling
Ovarian Carcinoma

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Trial Information

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.

Inclusion Criteria:

- Patients 18 years of age and ≤75 years of age

- Biopsy-proven ovarian, tubal or primary peritoneal epithelial adenocarcinomas;

- Performance status 0,1 (ECOG) ( table 2)

- Patients at high risk of clinical relapse: first remission stage III/IV who were
suboptimally debulked (residual disease >1 cm)

- Patients of any stage who have recurred and are in second chemotherapy induced
remission. Clinical remission defined as:

- absence of symptoms that may be related to disease

- imaging without abnormalities greater then or equal to 1 cm suspicious for
disease (no ascites)

- CA 125 obtained x 1 and <35 units/ml.

- Adequate end organ function, defined as the following:

- Total bilirubin < 1.5 x ULN

- SGOT and SGPT < 2.5 x UNL

- Creatinine < 1.5 x ULN

- ANC > 1.5 x 109/L

- Platelets > 100 x 109/L

- Weight ≥ 50 kg

Exclusion Criteria:

- Patients with performance status ECOG =2,3,4

- Patients who are on warfarin or prior therapeutic anticoagulation

- Patient has another primary malignancy that has required active intervention within 5
years, with the exception of basal cell skin cancer or a cervical carcinoma in situ.

- Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled
diabetes, chronic renal disease, or active uncontrolled infection).

- Patient who had a major surgery within 2 weeks prior to study entry

- Patients with the following lab abnormalities:

- WBC <3000

- absolute neutrophil count < 1,500

- hemoglobin <10 g/dL

- platelet < 100,000

- creatinine clearance <30 cc/min

- serum ALT, AST, or total bilirubin >1.5X the upper limit of normal

- Patients with known bleeding disorder

Type of Study:


Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Estimate the proportion of patients who complete an eight week course of once daily administration of fondaparinux (Arixtra).

Outcome Time Frame:

15 months

Safety Issue:


Principal Investigator

Boris Kobrinsky, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

NYU School of Medicine


United States: Institutional Review Board

Study ID:




Start Date:

January 2008

Completion Date:

November 2010

Related Keywords:

  • Ovarian Carcinoma
  • Pretreated Ovarian Carcinoma
  • Carcinoma
  • Ovarian Neoplasms
  • Neoplasms, Glandular and Epithelial



NYU Cancer Institute Clinical Cancer Center New York, New York  10016