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

March 16, 2015 updated by: NYU Langone Health

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

The purpose of this study is to assess feasibility and safety of using once daily Fondaparinux Sodium (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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Rationale:

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 disease.

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.

Hypothesis:

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.

Study Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10016
        • NYU Cancer Institute Clinical Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Estimate the proportion of patients who complete an eight week course of once daily administration of fondaparinux (Arixtra).
Time Frame: 15 months
15 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Time to Recurrence
Time Frame: 24 months
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NYU Langone Health

Collaborators

GlaxoSmithKline

Investigators

  • Principal Investigator: Boris Kobrinsky, M.D., NYU School of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2008

Primary Completion (Anticipated)

September 1, 2010

Study Completion (Anticipated)

November 1, 2010

Study Registration Dates

First Submitted

April 10, 2008

First Submitted That Met QC Criteria

April 10, 2008

First Posted (Estimate)

April 16, 2008

Study Record Updates

Last Update Posted (Estimate)

March 18, 2015

Last Update Submitted That Met QC Criteria

March 16, 2015

Last Verified

March 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 07-742

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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