Pro-coagulant Markers and Anticoagulant Failure in Cancer Patients at Risk for Recurrence of Venous Thromboembolism

Study Overview
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Brief Summary
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The presence of clots in the veins of arms and/or legs or lungs of Cancer patients decreases their quality of life, delays their treatment and may cause death. The best way to avoid new clots is by giving blood thinners before clots are formed, but even some patients who are taking blood thinners may form blood clots. A major problem is that it is difficult to know which patients form clots while they are receiving blood thinners, a situation called treatment failure. Several studies have shown that by doing blood tests that measure the formation of clots, the investigators could know if the patient is responding to the blood thinners. If this is proven, the investigators will be able to apply these tests to all patients.

Detailed Description
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Therapeutic failure in cancer patients at high risk for recurrence of Venous thromboembolism (VTE) may be as high as 20% and the risk of death from a recurrent episode of pulmonary embolism is at least 8%. Studies that have used pro-coagulant and thrombin generation markers support the notion that cancer is associated with a hypercoagulability state and that intensified doses of anticoagulation may be necessary to suppress this state. Thus, it may be possible that by using these tests, we would identify the patients that do not respond to standard doses of anticoagulation. To date, only few small studies have evaluated the use of pro-coagulant markers in cancer patients but this data is promising. Our study will measure pro-coagulant markers in cancer patients at risk for VTE recurrence to determine if there is a relationship between the changes in the levels of pro-coagulant markers and VTE recurrence while taking anticoagulation with low-molecular weight-heparin (LMWH). The evaluation of the pro-coagulant markers may enable new treatment strategies in cancer patients who fail their initial treatment. Patients will be stratified by a risk model developed by our group and will be validate with this study. This new approach has the potential to improve the recovery of patients, to reduce death and disability due to clots in the veins of legs or arms and/or lungs.

Official Title
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Analysis of Pro-coagulant and Thrombin-generation Markers for the Prediction of Therapeutic Failure in Cancer Patients at Risk for Recurrence of Venous Thromboembolism: A Pilot Study

Conditions
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Cancer, Venous Thromboembolism, Deep-Vein Thrombosis, Pulmonary Embolism

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with any type of cancer (except basal cell and squamous cell carcinoma of the skin) and at any stage of the disease or treatment Confirmed newly diagnosed acute symptomatic VTE (proximal DVT, PE, Arm DVT, Multiple SSPE only) Planned treatment of VTE with low-molecular weight heparin (LMWH) Age 18 years old or older. Exclusion Criteria: Planned cell transplant Patient receiving anticoagulation due to other clinical indications Patient who has received more than one therapeutic dose of LMWH Unable or unwilling to provide written, informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cancer patients<br>All cancer patients with a diagnosed acute symptomatic VTE episode. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative changes on biochemical markers | The following pro-coagulant and thrombin-generation markers will be measured: Prothrombin fragments F1+2; D-dimer, thrombin-antithrombin (TAT) Soluble P-selectin. For each patient, we will calculate baseline values and the relative changes (delta) of procoagulant and thrombin generation markers. The relative changes (delta) will be defined by the percentage of change in the marker at each visit relative to baseline measurement. | at initiation of anticoagulation (baseline); at 7-14 days; 21-35 days; 37- 44 days; 83-97 days; and 173-187 days after initiation of anticoagulation. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of treatment failure | This outcome will be measured by the proportion of cancer patients who might develop recurrent VTE while on 6-month treatment with anticoagulation within the time-frame of the study. | 6 months | 
| Correlation between treatment failure and markers | This outcome will be assessed by determining the best cutoff for each marker that would correctly classify success or failure to anticoagulation treatment | 6 months after treatment failure | 
| Compliance to anticoagulation treatment | Compliance to medication will be measured by review of the patient medication diary. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Venous Thrombosis, Coagulation factors, Blood