Enoxaparin Thromboprophylaxis in Cancer Patients With Elevated Tissue Factor Bearing Microparticles

Condition(s) targeted: Pancreatic Cancer; Lung Cancer; Colon Cancer

Intervention: Enoxaparin (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Beth Israel Deaconess Medical Center

Official(s) and/or principal investigator(s):
Jeffrey Zwicker, MD, Principal Investigator, Affiliation: Beth Israel Deaconess Medical Center

Overall contact:
Jeffrey Zwicker, MD, Phone: 617-667-9299

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 lung, colon, or pancreas 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.

Official title: A Randomized Controlled Trial of Enoxaparin Thromboprophylaxis in Cancer Patients With Elevated Tissue Factor Bearing Microparticles

Study design: Prevention, Randomized, Open Label, Parallel Assignment, Efficacy Study

Primary outcome: Assess the benefit of enoxaparin in preventing venous thromboembolic events in cancer patients with high levels of circulating tissue factor bearing microparticles (TFMP).

Secondary outcome:

To investigate the safety of prophylactic enoxaparin in cancer patients (major bleeding episodes).

To assess the impact of enoxaparin on overall survival.

To investigate the cumulative incidence of symptomatic or proximal venous thromboembolic events (VTE) at 6 months.

To investigate the cumulative incidence of total VTE in cancer patients with low TFMP compared with those with high TFMP not treated with enoxaparin.

To assess the influence of chemotherapy or enoxaparin on TFMP levels

To assess the association between absolute TFMP levels and thrombotic risk

Detailed description:

- Because no one knows which of the study options is best, participants will be

randomized into one of the following study groups. Participants who have high levels of TFMP in their blood will be in one of the two arms indicated.

- Arm A (High TFMP): Enoxaparin given subcutaneously (into the skin) daily for 6 months,

and lower extremity ultrasound performed every 2 months.

- Arm B (High TFMP): Observation, lower extremity ultrasound performed every 2 months.

- Arm C (Low TFMP): Observation, lower extremity ultrasound performed every 2 months.

- Every 2 months, participants will have a physical examination and will be asked

questions about their general health and specific questions about any problems they might be having. They will also have a lower extremity ultrasound and blood tests performed every 2 months.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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), colon (stage IV), or lung (unresectable stage III or IV).

- 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

- 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.

Jeffrey Zwicker, MD, Phone: 617-667-9299

Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, United States; Recruiting
Jeffrey Zwicker, MD, Principal Investigator

Massachusetts General Hospital, Boston, Massachusetts 02114, United States; Recruiting
David P. Ryan, MD, Principal Investigator

Mass General/North Shore Cancer Center, Danvers, Massachusetts 01923, United States; Recruiting
Rachel Rosovsky, MD, Principal Investigator

Starting date: May 2009
Last updated: July 27, 2009