Anti-Platelet and Statin Therapy to Prevent Cancer-Associated Thrombosis
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Detailed Description
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
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Aspirin+Asprin/Simvastatin+Observation (ASO) 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
81mg/day for 4 weeks
Drug: Simvastatin
Daily dose of Simvastatin for 4 weeks
Other: Observation
participants will be observed for thrombotic evens for 4 weeks
|
| Experimental: Aspirin+Observation+Asprin/Simvastatin (AOS) 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
81mg/day for 4 weeks
Drug: Simvastatin
Daily dose of Simvastatin for 4 weeks
Other: Observation
participants will be observed for thrombotic evens for 4 weeks
|
| Experimental: Aspirin/Simvastatin+Observation+Asprin (SOA) 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
81mg/day for 4 weeks
Drug: Simvastatin
Daily dose of Simvastatin for 4 weeks
Other: Observation
participants will be observed for thrombotic evens for 4 weeks
|
| Experimental: Aspirin/Simvastatin+Asprin+Observation (SAO) 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
81mg/day for 4 weeks
Drug: Simvastatin
Daily dose of Simvastatin for 4 weeks
Other: Observation
participants will be observed for thrombotic evens for 4 weeks
|
| Experimental: Observation+Aspirin/Simvastatin+Asprin (OSA) 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
81mg/day for 4 weeks
Drug: Simvastatin
Daily dose of Simvastatin for 4 weeks
Other: Observation
participants will be observed for thrombotic evens for 4 weeks
|
| Experimental: Observation+Aspirin+Asprin/Simvastatin (OAS) 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
81mg/day for 4 weeks
Drug: Simvastatin
Daily dose of Simvastatin for 4 weeks
Other: Observation
participants will be observed for thrombotic evens for 4 weeks
|
Outcome Measures
Primary Outcome Measures
- Change in average sP-selectin levels [at 16 weeks of treatment]
Change in sP-selectin levels as indicator of measure efficacy
Secondary Outcome Measures
- Frequency of major bleeding complications or clinically significant non-bleeding complications per patient [at 17 weeks after beginning treatment]
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.
- Change in average Platelet Factor 4 [at 16 weeks of treatment]
measure of efficacy using plasma level of platelet activation markers
- Change in average CD40 ligand [at 16 weeks of treatment]
measure of efficacy using plasma level of platelet activation markers
- Change in average serum thromboxane B2 [at 16 weeks of treatment]
measure of efficacy using plasma level of platelet activation markers
- Change in average serum VEGF [at 16 weeks of treatment]
measure of efficacy using plasma level of angiogenesis markers
- Change in average serum angiopoietin-2 [at 16 weeks of treatment]
measure of efficacy using plasma level of angiogenesis markers
- Change in average serum hepatocyte growth factor [at 16 weeks of treatment]
measure of efficacy using plasma level of angiogenesis markers
- Change in average serum PECAM [at 16 weeks of treatment]
measure of efficacy using plasma level of angiogenesis markers
- Change in average serum PDGF [at 16 weeks of treatment]
measure of efficacy using plasma level of angiogenesis markers
- Change in average plasma F1.2 [at 16 weeks of treatment]
measure of efficacy using plasma level of hemostatic activation markers
- Change in average plasma TAT complexes [at 16 weeks of treatment]
measure of efficacy using plasma level of hemostatic activation markers
- Change in average plasma D-dimer [at 16 weeks of treatment]
measure of efficacy using plasma level of hemostatic activation markers
- Change in the number of thrombotic events [17 weeks after beginning treatment]
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
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center | Cleveland | Ohio | United States | 44195 |
Sponsors and Collaborators
- Case Comprehensive Cancer Center
Investigators
- Principal Investigator: Alok A Khorana, MD, Case Comprehensive Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CASE8Y14