Trial record 1 of 1 for:    vcc1110
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Detecting the Impact of Statin Therapy On Lowering Risk of Venous Thrombo-Embolic Events (DISOLVE)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Steven Ades, University of Vermont
ClinicalTrials.gov Identifier:
NCT01524653
First received: January 20, 2012
Last updated: December 12, 2013
Last verified: December 2013
  Purpose

Patients with cancer have a high risk of developing venous blood clots or thromboembolism (VTE). In an effort to target patients at highest risk of VTE for thromboprophylaxis (protective treatment for blood clots), numerous studies have identified serum biomarkers for risk of future VTE. There is also increasing evidence pointing to a prophylactic effect of statin therapy on the risk of developing VTE in high-risk populations including patients with advanced cancer. The purpose of this research study is to find out whether treatment with rosuvastatin (the study drug) reduces the risk of VTE in patients with cancer receiving chemotherapy. This study is specifically investigating the impact of rosuvastatin therapy on serum biomarkers (D-dimer and others) that indicate a risk for VTE, as well as safety and tolerance of rosuvastatin therapy in this population.

This is a phase II randomized crossover study with two 3-4 week treatment periods during which all enrolled patients will receive 20 mg of rosuvastatin once a day by mouth or a matching placebo tablet. Approximately two tablespoons of blood will be collected for biomarker analysis at the beginning and end of each treatment period. After the first treatment period there will be a 3-5 week break where subjects will undergo a washout. Following this washout period every subject will "crossover" or begin taking the alternative therapy so everyone enrolled will receive the study drug either during the first or the second treatment period. Biomarker levels will be analyzed in both treatment periods and compared to baseline, with every patient acting as their own control.


Condition Intervention Phase
Venous Thromboembolism
Deep Vein Thrombosis
Neoplasms
Drug: Rosuvastatin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Impact of Rosuvastatin on Risk Markers of Venous Thromboembolism During Systemic Therapy for Advanced Cancer

Resource links provided by NLM:


Further study details as provided by University of Vermont:

Primary Outcome Measures:
  • To determine if rosuvastatin therapy reduces the risk of VTE in patients with cancer receiving chemotherapy, as measured by a decrease in D-dimer level with treatment compared to placebo [ Time Frame: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in Factor VIII [ Time Frame: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment) ] [ Designated as safety issue: No ]
  • To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in soluble P-selectin [ Time Frame: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment) ] [ Designated as safety issue: No ]
  • To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in C-reactive protein [ Time Frame: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment) ] [ Designated as safety issue: No ]
  • To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in Peak thrombin generation [ Time Frame: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment) ] [ Designated as safety issue: No ]
  • Adverse Events (CTCAE v4) associated with rosuvastatin therapy [ Time Frame: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment) ] [ Designated as safety issue: Yes ]
    Liver toxicity and rhabdomyolysis

  • Venous thromboembolism [ Time Frame: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment) ] [ Designated as safety issue: Yes ]
    Clinical signs of venous thromboembolism

  • To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in Plasminogen activator inhibitor-1 activity [ Time Frame: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment) ] [ Designated as safety issue: No ]
  • To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in Plasminogen activator inhibitor-1 protein concentration [ Time Frame: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment) ] [ Designated as safety issue: No ]
  • To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in tissue factor [ Time Frame: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment) ] [ Designated as safety issue: No ]
  • To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in Factor XIa [ Time Frame: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment) ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: March 2012
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rosuvastatin First, Placebo Last
This arm will receive rosuvastatin during the first treatment period followed by placebo in the second treatment period after washout.
Drug: Rosuvastatin
20 mg po od
Other Name: Crestor
Drug: Placebo
20 mg po od
Experimental: Placebo First, Rosuvastatin Last
This arm will receive placebo during the first treatment period followed by rosuvastatin in the second treatment period after washout.
Drug: Rosuvastatin
20 mg po od
Other Name: Crestor
Drug: Placebo
20 mg po od

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients > 18 years old with locally-advanced or metastatic cancers who are about to start or are already receiving any systemic chemotherapy or targeted therapy.
  • Estimated overall survival of ≥ 6 months
  • Anticipated duration of therapy ≥ 9 weeks (if 3-week cycle) or ≥ 12 weeks (if 2 or 4-week cycle). Systemic therapy is allowed to change if necessary, or to terminate, during this period

Exclusion Criteria:

  • Antithrombotic therapy including warfarin, dabigatran, low molecular weight heparin or unfractionated heparin. Patients taking aspirin may participate in this study.
  • Anti-angiogenic therapy with thalidomide or lenalidomide. Patients receiving bevacizumab may participate in this study.
  • Patients starting hormonal therapy exclusively, such as SERM or aromatase inhibitor therapy for breast cancer, or androgen-ablative therapy for prostate cancer.
  • Statin use within 3 months prior to enrolment
  • Adjuvant therapy in patients who have already received curative-intent local therapy (surgery or radiotherapy). Patients with glioblastoma starting adjuvant chemotherapy are an exception given the high likelihood of residual disease and risk of VTE in this population.
  • Asian descent as assessed by history. If either of the participant's parents is Asian (peoples of East, Southeast, and South Asia), a patient will be excluded due to slower metabolism of the drug and concerns regarding toxicity at the 20 mg dose level.
  • Urinary creatinine clearance of less than 40 ml/min based on reported MDRD GFR, present in FAHC metabolic profile reports, during the 14 day screening period.
  • AST or ALT elevation of greater than 3X upper limit of normal, during the 14 day screening period.
  • Patients with a known history of statin intolerance that was accompanied by severe adverse reaction.
  • Patients who are currently participating in another clinical trial involving an investigational medication if there is a known or suspected drug interaction with rosuvastatin or the statin class, or if the investigational agent is known or suspected to be associated with a significantly increased risk of thrombosis.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01524653

Locations
United States, Vermont
Fletcher Allen Health Care
Burlington, Vermont, United States, 05401
Sponsors and Collaborators
University of Vermont
Investigators
Principal Investigator: Steven Ades, MD, MSc University of Vermont
  More Information

Additional Information:
No publications provided

Responsible Party: Steven Ades, Assistant Professor of Medicine, University of Vermont
ClinicalTrials.gov Identifier: NCT01524653     History of Changes
Other Study ID Numbers: VCC 1110
Study First Received: January 20, 2012
Last Updated: December 12, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Vermont:
VTE
DVT
Chemo
Metastatic
Advanced
Systemic therapy
statin
biomarkers

Additional relevant MeSH terms:
Neoplasms
Thromboembolism
Thrombosis
Venous Thrombosis
Venous Thromboembolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Rosuvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014