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

Study Description

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Brief 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.

Condition or disease	Intervention/treatment	Phase
Ovarian Carcinoma	Drug: Fondaparinux	Phase 1

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	0 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	07-742 Phase I/ Feasibility Study of Short Term Fondaparinux (Arixtra) in Chemotherapy-Pretreated Ovarian Carcinoma Patients at High Risk of Progression
Study Start Date :	January 2008
Estimated Primary Completion Date :	September 2010
Estimated Study Completion Date :	November 2010

Arms and Interventions

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Intervention Details:

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

  • Arixtra
  • fondaparinux sodium

Outcome Measures

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Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Time to Recurrence [ Time Frame: 24 months ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Older Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Locations

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

Sponsors and Collaborators

New York University School of Medicine

GlaxoSmithKline

Investigators

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

More Information

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Responsible Party:	Boris Kobrinsky, New York University Cancer Institute
ClinicalTrials.gov Identifier:	NCT00659399 History of Changes
Other Study ID Numbers:	07-742
First Posted:	April 16, 2008
Last Update Posted:	March 18, 2015
Last Verified:	March 2015

Keywords provided by New York University School of Medicine:

Pretreated Ovarian Carcinoma

Additional relevant MeSH terms:

Carcinoma; Ovarian Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases	Gonadal Disorders; Fondaparinux; PENTA; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anticoagulants; Fibrinolytic Agents; Fibrin Modulating Agents