Back to resultsDetecting the Impact of Statin Therapy On Lowering Risk of Venous Thrombo-Embolic Events (DISOLVE) (DISOLVE)
Primary Purpose
Venous Thromboembolism, Deep Vein Thrombosis, Neoplasms
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Rosuvastatin
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Venous Thromboembolism focused on measuring VTE, DVT, Chemo, Metastatic, Advanced, Systemic therapy, statin, biomarkers
Eligibility 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.
Sites / Locations
- Fletcher Allen Health Care
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Rosuvastatin First, Placebo Last
Placebo First, Rosuvastatin Last
Arm Description
This arm will receive rosuvastatin during the first treatment period followed by placebo in the second treatment period after washout.
This arm will receive placebo during the first treatment period followed by rosuvastatin in the second treatment period after washout.
Outcomes
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
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
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
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
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
Adverse Events (CTCAE v4) associated with rosuvastatin therapy
Liver toxicity and rhabdomyolysis
Venous thromboembolism
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
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
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
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01524653
Brief Title
Detecting the Impact of Statin Therapy On Lowering Risk of Venous Thrombo-Embolic Events (DISOLVE)
Acronym
DISOLVE
Official Title
Impact of Rosuvastatin on Risk Markers of Venous Thromboembolism During Systemic Therapy for Advanced Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
March 2012 (undefined)
Primary Completion Date
July 1, 2016 (Actual)
Study Completion Date
September 1, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Vermont
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Venous Thromboembolism, Deep Vein Thrombosis, Neoplasms
Keywords
VTE, DVT, Chemo, Metastatic, Advanced, Systemic therapy, statin, biomarkers
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
38 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rosuvastatin First, Placebo Last
Arm Type
Experimental
Arm Description
This arm will receive rosuvastatin during the first treatment period followed by placebo in the second treatment period after washout.
Arm Title
Placebo First, Rosuvastatin Last
Arm Type
Experimental
Arm Description
This arm will receive placebo during the first treatment period followed by rosuvastatin in the second treatment period after washout.
Intervention Type
Drug
Intervention Name(s)
Rosuvastatin
Other Intervention Name(s)
Crestor
Intervention Description
20 mg po od
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
20 mg po od
Primary Outcome Measure Information:
Title
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)
Secondary Outcome Measure Information:
Title
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)
Title
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)
Title
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)
Title
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)
Title
Adverse Events (CTCAE v4) associated with rosuvastatin therapy
Description
Liver toxicity and rhabdomyolysis
Time Frame
baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
Title
Venous thromboembolism
Description
Clinical signs of 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)
Title
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)
Title
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)
Title
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)
Title
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven Ades, MD, MSc
Organizational Affiliation
University of Vermont
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fletcher Allen Health Care
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.vermontcancer.org/
Description
Vermont Cancer Center
Learn more about this trial
Detecting the Impact of Statin Therapy On Lowering Risk of Venous Thrombo-Embolic Events (DISOLVE)
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