Clinical trial NCT02285738: Anti-Platelet and Statin Therapy to Prevent Cancer-Associated Thrombosis
Official title: Anti-Platelet and Statin Therapy to Prevent Cancer-Associated Thrombosis: A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Solid Tumor
Cancer
Keywords: solid tumor, cancer, simvastatin, aspirin, blood clot, VTE, venous thromboembolism
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2014-11-07
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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

Eligibility 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.

Primary outcomes:
measure: Change in average sP-selectin levels
timeFrame: at 16 weeks of treatment
Secondary outcomes:
measure: Frequency of major bleeding complications or clinically significant non-bleeding complications per patient
timeFrame: at 17 weeks after beginning treatment
measure: Change in average Platelet Factor 4
timeFrame: at 16 weeks of treatment
measure: Change in average CD40 ligand
timeFrame: at 16 weeks of treatment
measure: Change in average serum thromboxane B2
timeFrame: at 16 weeks of treatment
measure: Change in average serum VEGF
timeFrame: at 16 weeks of treatment
measure: Change in average serum angiopoietin-2
timeFrame: at 16 weeks of treatment
measure: Change in average serum hepatocyte growth factor
timeFrame: at 16 weeks of treatment
measure: Change in average serum PECAM
timeFrame: at 16 weeks of treatment
measure: Change in average serum PDGF
timeFrame: at 16 weeks of treatment
measure: Change in average plasma F1.2
timeFrame: at 16 weeks of treatment
measure: Change in average plasma TAT complexes
timeFrame: at 16 weeks of treatment
measure: Change in average plasma D-dimer
timeFrame: at 16 weeks of treatment
measure: Change in the number of thrombotic events
timeFrame: 17 weeks after beginning treatment
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Case Comprehensive Cancer Center
name: Alok A Khorana, MD
role: PRINCIPAL_INVESTIGATOR
References: