Dr. Zwicker is the principle investigator of the MicroTEC trial at Beth Israel Deaconess Medical Center.

Study Titles:

  1. A Randomized Controlled Trial of Enoxaparin Thromboprophylaxis in Cancer Patients With Elevated Tissue Factor-Bearing Microparticles (MicroTEC)

  2. A Study of Dalteparin Prophylaxis in High-Risk Ambulatory Cancer Patients (PHACS)

Coordinators:

  1. Principle Investigator: Jeffrey Zwicker, Beth Israel Deaconess Medical Center, Boston, MA

  2. Principle Investigator: Charles Francis, University of Rochester, Rochester, NY

Sponsors:

  1. NHLBI, Sanofi

  2. NHLBI, Eisai

Clinicaltrials.gov Identifiers:

Participating Centers:

  1. Beth Israel Deaconess Medical Center, University of Southern California, Boston VA Healthcare, Mass General/North Shore Cancer Center, Mt. Auburn Hospital, Lahey Clinic, and York Hospital

  2. University of Rochester Medical Center and Duke University School of Medicine

Accrual Goals:

  1. 70 patients

  2. 229 patients

Study Designs:

  1. MicroTEC is a phase II, randomized, three-arm study for patients with advanced cancer (pancreatic, colon, non-small-cell lung, gastric) within four weeks of initiating first-line or second-line chemotherapy. Following measurement of microparticles, those with elevated levels are randomized to enoxaparin, 40 mg subcutaneous daily for two months, or observation alone. Individuals with low microparticle levels are observed without randomization. All patients undergo bilateral lower extremity ultrasound at baseline and at the completion of the two-month study. Patients and study physicians are blinded to microparticle status in the observation arms. The primary endpoint is the cumulative incidence of symptomatic venous thromboembolic events or deep-vein thrombosis documented by the lower extremity ultrasound performed at the end of the study period.

  2. The PHACS study is a phase III, randomized study of dalteparin or observation in cancer patients starting systemic chemotherapy and designated as high risk for venous thromboembolic events based on a scoring system that includes the following parameters: high-risk site of cancer (stomach, pancreas, lung, lymphoma, gynecologic, bladder, and testicular); hemoglobin ≤ 10 g/dL or planned erythropoiesis-stimulating agents; platelet count of ≥350,000/mm3; total leukocyte count ≥ 11,000/mm3; body mass index ≥ 35 kg/m2. The primary endpoint is a reduction in venous thromboembolic events at three months.

Rationale:

The MicroTEC and PHACS studies target primary thromboprophylaxis to high-risk cancer outpatients. The rationale for the MicroTEC study is based on the observation that elevated levels of circulating tissue-factor bearing microparticles represent a significant risk factor for development of venous thromboembolic events in cancer patients.1  Similarly, Khorana and colleagues developed a risk model that stratifies outpatients with cancer into risk categories based on site of cancer, hemoglobin concentration, platelet count, leukocyte count, and body mass index.2 

Comment:

Although it is well established that patients with cancer have an abnormally high rate of thrombosis, a standard approach to anticoagulant prophylaxis in the setting of malignancy has yet to emerge. Recently, two large phase III trials demonstrated efficacy in primary thromboprophylaxis using low-molecular-weight heparins in cancer patients, with a 2 percent absolute reduction in venous thromboembolic events observed.3,4  The MicroTEC and PHACS studies are designed to target anticoagulation in high-risk cancer populations either by measuring a biomarker of thrombotic risk (tissue factor-bearing microparticles) or by using a validated risk model. By aiming at a defined target population, the efficacy of thromboprophylaxis in patients with cancer may be improved beyond that observed in unstratified patient populations.

1.
Zwicker JI, Liebman HA, Neuberg D, et al. Tumorderived tissue factor-bearing microparticles are associated with venous thromboembolic events in malignancy. Clin Cancer Res. 2009;15:6830-6840.
2.
Khorana AA, Kuderer NM, Culakova E, et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111:4902-4907.