Enoxaparin Thromboprophylaxis in Cancer Patients With Elevated Tissue Factor Bearing Microparticles

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.

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.