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

Ovarian Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00659399
• Other study ID #: 07-742
• Status: Withdrawn
• Phase: Phase 1
• First received: April 10, 2008
• Last updated: March 16, 2015
• Start date: January 2008
• Est. completion date: November 2010

Study information

• Verified date: March 2015
• Source: New York University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 2010
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Fondaparinux
Arixtra 2.5 mg by subcutaneous injection once daily for 8 weeks or until disease recurrence or grade 3, 4 adverse events.

Locations

Country	Name	City	State
United States	NYU Cancer Institute Clinical Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
New York University School of Medicine	GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Estimate the proportion of patients who complete an eight week course of once daily administration of fondaparinux (Arixtra).		15 months	Yes
Secondary	Time to Recurrence		24 months	No