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

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ClinicalTrials.gov Identifier: NCT02285738
Recruitment Status : Completed
First Posted : November 7, 2014
Last Update Posted : May 8, 2019
Sponsor:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE November 5, 2014
First Posted Date  ICMJE November 7, 2014
Last Update Posted Date May 8, 2019
Actual Study Start Date  ICMJE December 30, 2014
Actual Primary Completion Date July 17, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 6, 2014)
Change in average sP-selectin levels [ Time Frame: at 16 weeks of treatment ]
Change in sP-selectin levels as indicator of measure efficacy
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02285738 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 12, 2014)
  • Frequency of major bleeding complications or clinically significant non-bleeding complications per patient [ Time Frame: 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 [ Time Frame: at 16 weeks of treatment ]
    measure of efficacy using plasma level of platelet activation markers
  • Change in average CD40 ligand [ Time Frame: at 16 weeks of treatment ]
    measure of efficacy using plasma level of platelet activation markers
  • Change in average serum thromboxane B2 [ Time Frame: at 16 weeks of treatment ]
    measure of efficacy using plasma level of platelet activation markers
  • Change in average serum VEGF [ Time Frame: at 16 weeks of treatment ]
    measure of efficacy using plasma level of angiogenesis markers
  • Change in average serum angiopoietin-2 [ Time Frame: at 16 weeks of treatment ]
    measure of efficacy using plasma level of angiogenesis markers
  • Change in average serum hepatocyte growth factor [ Time Frame: at 16 weeks of treatment ]
    measure of efficacy using plasma level of angiogenesis markers
  • Change in average serum PECAM [ Time Frame: at 16 weeks of treatment ]
    measure of efficacy using plasma level of angiogenesis markers
  • Change in average serum PDGF [ Time Frame: at 16 weeks of treatment ]
    measure of efficacy using plasma level of angiogenesis markers
  • Change in average plasma F1.2 [ Time Frame: at 16 weeks of treatment ]
    measure of efficacy using plasma level of hemostatic activation markers
  • Change in average plasma TAT complexes [ Time Frame: at 16 weeks of treatment ]
    measure of efficacy using plasma level of hemostatic activation markers
  • Change in average plasma D-dimer [ Time Frame: at 16 weeks of treatment ]
    measure of efficacy using plasma level of hemostatic activation markers
  • Change in the number of thrombotic events [ Time Frame: 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
Original Secondary Outcome Measures  ICMJE
 (submitted: November 6, 2014)
  • Frequency of major bleeding complications or clinically significant non-bleeding complications per patient [ Time Frame: 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 [ Time Frame: at 16 weeks of treatment ]
    measure of efficacy using plasma level of platelet activation markers
  • Change in average CD40 ligand [ Time Frame: at 16 weeks of treatment ]
    measure of efficacy using plasma level of platelet activation markers
  • Change in average serum thromboxane B2 [ Time Frame: at 16 weeks of treatment ]
    measure of efficacy using plasma level of platelet activation markers
  • Change in average serum VEGF [ Time Frame: at 16 weeks of treatment ]
    measure of efficacy using plasma level of angiogenesis markers
  • Change in average serum angiopoietin-2 [ Time Frame: at 16 weeks of treatment ]
    measure of efficacy using plasma level of angiogenesis markers
  • Change in average serum hepatocyte growth factor [ Time Frame: at 16 weeks of treatment ]
    measure of efficacy using plasma level of angiogenesis markers
  • Change in average serum PECAM [ Time Frame: at 16 weeks of treatment ]
    measure of efficacy using plasma level of angiogenesis markers
  • Change in average serum PDGF [ Time Frame: at 16 weeks of treatment ]
    measure of efficacy using plasma level of angiogenesis markers
  • Change in average plasma F1.2 [ Time Frame: at 16 weeks of treatment ]
    measure of efficacy using plasma level of hemostatic activation markers
  • Change in average plasma TAT complexes [ Time Frame: at 16 weeks of treatment ]
    measure of efficacy using plasma level of hemostatic activation markers
  • Change in average plasma D-dimer [ Time Frame: at 16 weeks of treatment ]
    measure of efficacy using plasma level of hemostatic activation markers
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Anti-Platelet and Statin Therapy to Prevent Cancer-Associated Thrombosis
Official Title  ICMJE Anti-Platelet and Statin Therapy to Prevent Cancer-Associated Thrombosis: A Pilot Study
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

Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE
  • Solid Tumor
  • Cancer
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
    Interventions:
    • Drug: Aspirin
    • Drug: Simvastatin
    • Other: Observation
  • 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
    Interventions:
    • Drug: Aspirin
    • Drug: Simvastatin
    • Other: Observation
  • 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
    Interventions:
    • Drug: Aspirin
    • Drug: Simvastatin
    • Other: Observation
  • 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.
    Interventions:
    • Drug: Aspirin
    • Drug: Simvastatin
    • Other: Observation
  • 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.
    Interventions:
    • Drug: Aspirin
    • Drug: Simvastatin
    • Other: Observation
  • 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.
    Interventions:
    • Drug: Aspirin
    • Drug: Simvastatin
    • Other: Observation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 22, 2019)
17
Original Estimated Enrollment  ICMJE
 (submitted: November 6, 2014)
42
Actual Study Completion Date  ICMJE October 1, 2018
Actual Primary Completion Date July 17, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02285738
Other Study ID Numbers  ICMJE CASE8Y14
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Case Comprehensive Cancer Center
Study Sponsor  ICMJE Case Comprehensive Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Alok A Khorana, MD Case Comprehensive Cancer Center
PRS Account Case Comprehensive Cancer Center
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP