Enoxaparin Thromboprophylaxis in Cancer Patients With Elevated Tissue Factor Bearing Microparticles

Phase 2

Completed

• Conditions: Advanced Pancreatic, Colon, Lung, Gastric and Ovarian Cancer
• Interventions: Drug: Enoxaparin

• Registration Number: NCT00908960
• Lead Sponsor: Beth Israel Deaconess Medical Center

Brief Summary

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.

Detailed Description

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 "detectable" 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.

Study Timeline

• Study Start: 2009-05
• Study First Submitted: 2009-05-26
• Study First Submitted QC: 2009-05-26
• Study First Posted: 2009-05-27
• Primary Completion: 2012-04
• Study Completion: 2012-10
• Results First Submitted: 2013-07-22
• Results First Submitted QC: 2013-10-22
• Results First Posted: 2013-12-12
• Status Verified: 2017-11
• Last Update Submitted: 2017-11-22
• Last Update Posted: 2017-12-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
High TFMP: Enoxaparin	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.

Primary Outcome Measures

Name	Time	Method
2-Month Cumulative Incidence of VTE	Assessment with lower extremity ultrasound occured at day 60/ month 2	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Assessed up to approximately 30 months	Overall survival is defined as the time from study entry to death or date last known alive and estimated using Kaplan-Meier (KM) methods.
Incidence of Major Hemorrhage Events	Assessed during the 60 day therapy	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)

Trial Locations

Locations (5)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Southern California-Keck School of Medicine; 🇺🇸 Los Angeles, California, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Mass General/North Shore Cancer Center; 🇺🇸 Danvers, Massachusetts, United States

VA Boston Healthcare System; 🇺🇸 Boston, Massachusetts, United States