Enoxaparin Thromboprophylaxis In Cancer Patients With Elevated Tissue Factor Bearing Microparticles

Study Overview

Enoxaparin Thromboprophylaxis in Cancer Patients With Elevated Tissue Factor Bearing Microparticles

Research studies have shown a strong association between cancer and blood clots in the veins (also known as deep vein thrombosis). These blood clots can flow to the lungs (pulmonary embolism) which in severe cases may be life threatening. The purpose of this research study is to see if enoxaparin is effective in preventing blood clots in the veins in participants who have cancer of the pancreas, colorectal, non-small cell lung, ovary, or gastric and also have high levels of tissue factor bearing microparticles in their blood (TFMP). TFMP are small particles that are generated from different types of blood cells in the body. In people who have cancer, TFMP are thought to be generated from cancer cells and may represent a risk factor for deep vein thrombosis. Enoxaparin has been used to prevent formation of blood clots in patients after abdominal or orthopedic surgery and in patients who suffer from a severe medical illness. Based on these studies, we are investigating to see if it prevents thrombosis in people with certain types of cancer.

The study was a randomized phase II trial to evaluate the cumulative incidence of VTE in cancer outpatients. At baseline, measurement of tissue factor-bearing microparticles (TFMP) was performed by impedance-based flow cytometry based on established methods. (Zwicker et al, 2009) Patients were classified as having high or low TFMP levels based on a reference repository of plasmas from sixty cancer patients. The top tercile of tissue factor-bearing microparticle concentrations from the reference specimens (3.5 x 104 microparticles/µl) was considered a cutoff for "high" and corresponds with previously described ⋞tectable" levels. Patients with high levels were randomized (2:1) to enoxaparin 40 mg subcutaneously once daily or observation. Randomization was stratified based on cancer diagnosis. Low TFMP patients were observed without anticoagulation. Both the treating physicians and patients were blinded to microparticle status in the observation arms.

Advanced Pancreatic, Colon, Lung, Gastric and Ovarian Cancer

DRUG: Enoxaparin

08-378

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 Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2009-05-26	Results First Submitted 2013-07-22	Last Update Submitted that met QC Criteria 2017-11-22
First Submitted that Met QC Criteria 2009-05-26	Results First Submitted that Met QC Criteria 2013-10-22	Last Update Posted (ACTUAL) 2017-12-19
First Posted (ACTUAL) 2009-05-27	Results First Posted 2013-12-12	Last Verified 2017-11

Study Plan

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

Design Details

Primary Purpose:
Prevention

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: High TFMP: Enoxaparin Patients received enoxaparin 40 mg subcutaneously once daily for 2 months (60 days).Only patients with high TFMP status at baseline were randomized to treatment or observation.	DRUG: Enoxaparin
NO_INTERVENTION: High TFMP: Observation Patients undergo observation until evaluation with a lower extremity ultrasound at 2 months (day 60). Only patients with high TFMP status at baseline were randomized to treatment or observation.
NO_INTERVENTION: Low TFMP: Observation Patients undergo observation until evaluation with a lower extremity ultrasound at 2 months (day 60). Patients with low TFMP status at baseline were directly assigned to observation.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: High TFMP: Enoxaparin

Patients received enoxaparin 40 mg subcutaneously once daily for 2 months (60 days).Only patients with high TFMP status at baseline were randomized to treatment or observation.

DRUG: Enoxaparin

NO_INTERVENTION: High TFMP: Observation

Patients undergo observation until evaluation with a lower extremity ultrasound at 2 months (day 60). Only patients with high TFMP status at baseline were randomized to treatment or observation.

NO_INTERVENTION: Low TFMP: Observation

Patients undergo observation until evaluation with a lower extremity ultrasound at 2 months (day 60). Patients with low TFMP status at baseline were directly assigned to observation.

Primary Outcome Measures	Measure Description	Time Frame
2-Month Cumulative Incidence of VTE	2-month cumulative incidence of venous thromboembolism (VTE) is the probability of experiencing within 2 months of study entry the following events: any symptomatic proximal or distal lower extremity deep vein thrombosis, symptomatic pulmonary embolism or fatal pulmonary embolism diagnosed by autopsy, or asymptomatic proximal deep vein thrombosis diagnosed by screening compression ultrasound.	Assessment with lower extremity ultrasound occured at day 60/ month 2

Secondary Outcome Measures	Measure Description	Time Frame
Incidence of Major Hemorrhage Events	Incidence is the number of patients experiencing at least one major hemorrhage events as defined according to International Society on Thrombosis and Haemostasis (ISTH) guidelines. (Schulman and Kearon 2005)	Assessed during the 60 day therapy
Overall Survival	Overall survival is defined as the time from study entry to death or date last known alive and estimated using Kaplan-Meier (KM) methods.	Assessed up to approximately 30 months

Contacts and Locations

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

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Histologically confirmed malignancy that is metastatic or unresectable and for which standard curative therapies do not exist. Eligible malignancies include:

Adenocarcinoma of the pancreas (locally advanced or metastatic)
Colorectal (stage IV)
Non-small cell lung (unresectable stage III or IV)
Relapsed ovarian or stage IV
Surgically unresectable or metastatic gastric adenocarcinoma
First or second line therapy (within 4 weeks of initiating therapy).
Minimum age 18 years
Life expectancy of greater than 6 months
ECOG Performance Status 0, 1, or 2 (Karnofsky 60% or greater).
Participants must have normal organ and marrow function as outlined in the protocol.

Participants may not be receiving any other study agents.
Known brain metastases should be excluded from this clinical trial because of their poor prognosis and higher potential for intracranial hemorrhage.
Prior history of documented venous thromboembolic event or pulmonary embolism within the last 5 years years (excluding central line associated events whereby patients completed anticoagulation > 3 months previously)
Active bleeding or high risk for bleeding (e.g. known acute gastrointestinal ulcer)
Any history of significant hemorrhage (requiring hospitalization or transfusion) outside of a surgical setting within the last 5 years
History of allergic reactions attributed to compounds of similar chemical or biologic composition to enoxaparin or heparin.
History of heparin-induced thrombocytopenia
Presence of coagulopathy (PT or PTT> 1.5 x upper limit of normal)
Familial bleeding diathesis
Known diagnosis of disseminated intravascular coagulation
Currently receiving anticoagulant therapy
Current use of aspirin (>81mg daily), Clopidogrel (Plavix), cilostazol (Pletal), aspirin-dipyridamole (Aggrenox), or regular use of non-steroidal anti-inflammatory agents more than twice weekly. Maximum dose of ibuprofen is 400mg no more than twice per week.
Uncontrolled intercurrent illness including, but not limited to, ongoing active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Collaborators and Investigators

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

Massachusetts General Hospital
North Shore Medical Center
University of Southern California
VA Boston Healthcare System
Sanofi

Investigators

PRINCIPAL_INVESTIGATOR: Jeffrey Zwicker, MD, Beth Israel Deaconess Medical Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Zwicker JI, Liebman HA, Bauer KA, Caughey T, Campigotto F, Rosovsky R, Mantha S, Kessler CM, Eneman J, Raghavan V, Lenz HJ, Bullock A, Buchbinder E, Neuberg D, Furie B. Prediction and prevention of thromboembolic events with enoxaparin in cancer patients with elevated tissue factor-bearing microparticles: a randomized-controlled phase II trial (the Microtec study). Br J Haematol. 2013 Feb;160(4):530-7. doi: 10.1111/bjh.12163. Epub 2012 Dec 13.
Rutjes AW, Porreca E, Candeloro M, Valeriani E, Di Nisio M. Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst Rev. 2020 Dec 18;12(12):CD008500. doi: 10.1002/14651858.CD008500.pub5.

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