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

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

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.

Study Overview

• Status: Completed
• Conditions: Cancer; Solid Tumor
• Intervention / Treatment: Drug: Aspirin; Drug: Simvastatin; Other: Observation

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 Type: Interventional
• Enrollment (Actual): 17
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Investigators: Principal Investigator: Alok A Khorana, MD, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2014
• Primary Completion (Actual): July 17, 2017
• Study Completion (Actual): October 1, 2018

Study Registration Dates

• First Submitted: November 5, 2014
• First Submitted That Met QC Criteria: November 6, 2014
• First Posted (Estimate): November 7, 2014

Study Record Updates

• Last Update Posted (Actual): May 8, 2019
• Last Update Submitted That Met QC Criteria: May 6, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: solid tumor, cancer, simvastatin, aspirin, blood clot, VTE, venous thromboembolism
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Aspirin; Simvastatin
• Other Study ID Numbers: CASE8Y14

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No