Enoxaparin Thromboprophylaxis in Cancer Patients With Elevated Tissue Factor Bearing Microparticles

NCT00908960 | Completed Phase 2 Results DMC

• 1 other identifier: 08-378
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 5

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.

Conditions

Advanced Pancreatic, Colon, Lung, Gastric and Ovarian Cancer

Keywords

enoxaparin

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Incidence of Major Hemorrhage Events

  Assessed during the 60 day therapy

• Overall Survival

  Assessed up to approximately 30 months

Study Arms (3)

High TFMP: Enoxaparin

EXPERIMENTAL

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

High TFMP: Observation

NO INTERVENTION

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.

Low TFMP: Observation

NO INTERVENTION

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.

Interventions

Enoxaparin DRUG

Also known as: Lovenox

High TFMP: Enoxaparin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Massachusetts General Hospital: collaborator
• North Shore Medical Center: collaborator
• University of Southern California: collaborator
• VA Boston Healthcare System: collaborator
• Sanofi: collaborator

Study Sites (5)

University of Southern California-Keck School of Medicine

Los Angeles, California, 90033, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

VA Boston Healthcare System

Boston, Massachusetts, 02130, United States

Location

Mass General/North Shore Cancer Center

Danvers, Massachusetts, 01923, United States

Location

Related Publications (2)

• 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.

  PMID: 23240761 RESULT

• 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.

  PMID: 33337539 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Enoxaparin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Jeffrey Zwicker, MD
• Organization: Beth Israel Deaconess Medical Center

jzwicker@bidmc.harvard.edu

617-667-9299

Study Officials

• Jeffrey Zwicker, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending Physician

Study Record Dates

• First Submitted: May 26, 2009
• First Posted: May 27, 2009
• Study Start: May 1, 2009
• Primary Completion: April 1, 2012
• Study Completion: October 1, 2012
• Last Updated: December 19, 2017
• Results First Posted: December 12, 2013

Record last verified: 2017-11

Locations

US (5)