Anti-Platelet and Statin Therapy to Prevent Cancer-Associated Thrombosis

Study Overview
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Brief Summary
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This research study examines the safety and feasibility of aspirin with or without Simvastatin in solid tumor patients at risk for VTE (Venous Thromboembolism - or blood clots - in the arms, lets, lungs, or other part of the body). One-fifth of all thrombotic (clotting) events occur in patients that have cancer. Changes in sP-selectin will be used as a measure of efficacy. We have chosen sP-selectin as the primary marker because of its role in hemostasis, because it is predictive of thrombosis in cancer patients and because of promising preliminary data. We expect that sP-selectin levels will be elevated in patients before therapy with aspirin and/or statin, but that these levels will fall significantly during treatment, rise during the observation phase, and fall during the second study period. Patients who take part in the study have been diagnosed with a solid tumor cancer and are considered to be intermediate to high risk for VTE. The standard of care is to give chemotherapy for solid tumors and treat clots which develop using blood thinners.

Detailed Description
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Objectives Primary: To determine efficacy of aspirin with and without simvastatin in solid tumor patients at high- or intermediate-risk for VTE, in reducing markers of platelet activation, levels of inflammatory and angiogenic cytokines measured using high-throughput approaches, and clinical and investigational measures of hemostatic activation. Secondary: To determine safety and feasibility of aspirin with or without simvastatin in solid tumor patients at high- or intermediate-risk for VTE

Official Title
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Anti-Platelet and Statin Therapy to Prevent Cancer-Associated Thrombosis: A Pilot Study

Conditions
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Solid Tumor, Cancer

Intervention / Treatment
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* Drug: Aspirin
* Drug: Simvastatin
* Other: Observation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic diagnosis of malignancy of a solid organ or lymphoma Planned to initiate a new systemic chemotherapy regimen (including patients starting on first chemotherapy or patients previously treated but starting on a new regimen) VTE Risk Score ≥1 Written, informed consent. Exclusion Criteria: Hematologic malignancies including acute and chronic leukemias, myelodysplastic syndromes, lymphoma and myeloma Primary brain tumors Active bleeding or high risk of bleeding in the opinion of the investigator Hepatic dysfunction (elevated transaminases or bilirubin > 3 times normal) Planned stem cell transplant Life expectancy < 6 months Acute or chronic renal insufficiency with creatinine clearance < 30 mL/min Pregnancy Known allergy to or prior intolerance of aspirin and/or simvastatin. Ongoing anticoagulant, statin and/or anti-platelet therapy.

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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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aspirin+Asprin/Simvastatin+Observation (ASO)<br>Aspirin 81mg/day for 4 weeks followed by 2-week washout, followed by 4 weeks of Aspirin 81mg/day with daily dose of Simvastatin with a 2-week washout period, ending with 4 weeks of observation | Drug: Aspirin<br>* 81mg/day for 4 weeks<br>Drug: Simvastatin<br>* Daily dose of Simvastatin for 4 weeks<br>Other: Observation<br>* participants will be observed for thrombotic evens for 4 weeks<br>|
| Experimental: Aspirin+Observation+Asprin/Simvastatin (AOS)<br>Aspirin 81mg/day for 4 weeks followed by 2-week washout, followed by 4 weeks of observation with 2-week washout, ending with Aspirin 81mg/day with daily dose of Simvastatin | Drug: Aspirin<br>* 81mg/day for 4 weeks<br>Drug: Simvastatin<br>* Daily dose of Simvastatin for 4 weeks<br>Other: Observation<br>* participants will be observed for thrombotic evens for 4 weeks<br>|
| Experimental: Aspirin/Simvastatin+Observation+Asprin (SOA)<br>Aspirin 81mg/day for 4 weeks with daily dose of Simvastatin followed by 2-week washout, followed by 4 weeks of observation with 2-week washout, ending with Aspirin 81mg/day | Drug: Aspirin<br>* 81mg/day for 4 weeks<br>Drug: Simvastatin<br>* Daily dose of Simvastatin for 4 weeks<br>Other: Observation<br>* participants will be observed for thrombotic evens for 4 weeks<br>|
| Experimental: Aspirin/Simvastatin+Asprin+Observation (SAO)<br>Aspirin 81mg/day for 4 weeks with daily dose of Simvastatin followed by 2-week washout, followed by 4 weeks of Aspirin 81mg/day and a 2-week washout, ending with observation for 4 weeks. | Drug: Aspirin<br>* 81mg/day for 4 weeks<br>Drug: Simvastatin<br>* Daily dose of Simvastatin for 4 weeks<br>Other: Observation<br>* participants will be observed for thrombotic evens for 4 weeks<br>|
| Experimental: Observation+Aspirin/Simvastatin+Asprin (OSA)<br>Observation for 4 weeks with 2-week washout, followed by Aspirin 81mg/day for 4 weeks with daily dose of Simvastatin followed by 2-week washout, ending with Aspirin 81mg/day for 4 weeks. | Drug: Aspirin<br>* 81mg/day for 4 weeks<br>Drug: Simvastatin<br>* Daily dose of Simvastatin for 4 weeks<br>Other: Observation<br>* participants will be observed for thrombotic evens for 4 weeks<br>|
| Experimental: Observation+Aspirin+Asprin/Simvastatin (OAS)<br>Observation for 4 weeks with 2-week washout, followed by Aspirin 81mg/day for 4 weeks followed by 2-week washout, ending with Aspirin 81mg/day for 4 weeks with daily dose of Simvastatin. | Drug: Aspirin<br>* 81mg/day for 4 weeks<br>Drug: Simvastatin<br>* Daily dose of Simvastatin for 4 weeks<br>Other: Observation<br>* participants will be observed for thrombotic evens for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in average sP-selectin levels | Change in sP-selectin levels as indicator of measure efficacy | at 16 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of major bleeding complications or clinically significant non-bleeding complications per patient | The safety endpoint will be bleeding complications over 17 weeks (16 weeks of study plus an additional week of observation). This will include major bleeding events and clinically significant non-major bleeding events. A bleeding event will be defined as major if it satisfies one or more of the following: decrease in hemoglobin of 2 g/dL or more, leads to transfusion of two or more units of blood or packed cells, occurs in a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial) or leads to death. Clinically significant, non-major bleeding will be defined as bleeding that does not meet the criteria for major bleeding, and has at least one of the following characteristics: multiple-source bleeding; spontaneous hematoma >25 cm2; epistaxis >5 min; macroscopic hematuria not related to instrumentation; spontaneous rectal bleeding; gingival bleeding > 5 min; hemoptysis; hematemesis; or prolonged bleeding (> 5 min) after venipuncture. | at 17 weeks after beginning treatment | 
| Change in average Platelet Factor 4 | measure of efficacy using plasma level of platelet activation markers | at 16 weeks of treatment | 
| Change in average CD40 ligand | measure of efficacy using plasma level of platelet activation markers | at 16 weeks of treatment | 
| Change in average serum thromboxane B2 | measure of efficacy using plasma level of platelet activation markers | at 16 weeks of treatment | 
| Change in average serum VEGF | measure of efficacy using plasma level of angiogenesis markers | at 16 weeks of treatment | 
| Change in average serum angiopoietin-2 | measure of efficacy using plasma level of angiogenesis markers | at 16 weeks of treatment | 
| Change in average serum hepatocyte growth factor | measure of efficacy using plasma level of angiogenesis markers | at 16 weeks of treatment | 
| Change in average serum PECAM | measure of efficacy using plasma level of angiogenesis markers | at 16 weeks of treatment | 
| Change in average serum PDGF | measure of efficacy using plasma level of angiogenesis markers | at 16 weeks of treatment | 
| Change in average plasma F1.2 | measure of efficacy using plasma level of hemostatic activation markers | at 16 weeks of treatment | 
| Change in average plasma TAT complexes | measure of efficacy using plasma level of hemostatic activation markers | at 16 weeks of treatment | 
| Change in average plasma D-dimer | measure of efficacy using plasma level of hemostatic activation markers | at 16 weeks of treatment | 
| Change in the number of thrombotic events | the number of thrombotic events measured by the number of events related to venus thrombosis, pulmonary embolism, visceral vein thrombosis as well as arterial thromboembolic events including stroke, myocardial infarction or arterial embolism | 17 weeks after beginning treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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solid tumor, cancer, simvastatin, aspirin, blood clot, VTE, venous thromboembolism