Enoxaparin Thromboprophylaxis in Cancer Patients With Elevated Tissue Factor Bearing Microparticles

NCT ID: NCT00908960

Last Updated: 2017-12-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2012-10-31

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.

Conditions

Advanced Pancreatic, Colon, Lung, Gastric and Ovarian Cancer

Keywords

enoxaparin

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Enoxaparin

Intervention Type: DRUG

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Enoxaparin

Intervention Type: DRUG

Other Intervention Names

Lovenox

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

North Shore Medical Center

OTHER

Sponsor Role: collaborator

University of Southern California

OTHER

Sponsor Role: collaborator

VA Boston Healthcare System

FED

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: collaborator

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Jeffrey Zwicker, MD

Attending Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeffrey Zwicker, MD

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

Locations

University of Southern California-Keck School of Medicine

Los Angeles, California, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

VA Boston Healthcare System

Boston, Massachusetts, United States

Mass General/North Shore Cancer Center

Danvers, Massachusetts, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 23240761 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33337539 (View on PubMed)

Other Identifiers

08-378

Identifier Type: -

Identifier Source: org_study_id