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

Purpose

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	Intervention	Phase
Ovarian Carcinoma	Drug: Fondaparinux	Phase 1


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Ovarian Cancer

Drug Information available for: Fondaparinux Fondaparinux sodium

Genetic and Rare Diseases Information Center resources: Ovarian Cancer Ovarian Epithelial Cancer

U.S. FDA Resources

Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:

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

Secondary Outcome Measures:

Time to Recurrence [ Time Frame: 24 months ] [ Designated as safety issue: No ]


Estimated Enrollment:	15
Study Start Date:	January 2008
Estimated Study Completion Date:	November 2010
Estimated Primary Completion Date:	September 2010 (Final data collection date for primary outcome measure)

Intervention Details:

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

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.

Eligibility


Ages Eligible for Study:	18 Years to 75 Years
Genders 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00659399

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

No publications provided


Responsible Party:	Boris Kobrinsky, New York University Cancer Institute
ClinicalTrials.gov Identifier:	NCT00659399 History of Changes
Other Study ID Numbers:	07-742
Study First Received:	April 10, 2008
Last Updated:	October 20, 2009
Health Authority:	United States: Institutional Review Board

Keywords provided by New York University School of Medicine:


Pretreated Ovarian Carcinoma

Additional relevant MeSH terms:


Neoplasms, Glandular and Epithelial Ovarian Neoplasms Adnexal Diseases Endocrine Gland Neoplasms Endocrine System Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Neoplasms Neoplasms by Histologic Type Neoplasms by Site Ovarian Diseases	Urogenital Neoplasms Fondaparinux PENTA Anticoagulants Cardiovascular Agents Fibrin Modulating Agents Fibrinolytic Agents Hematologic Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Therapeutic Uses

ClinicalTrials.gov processed this record on March 03, 2015