Pilot Study of Rosuvastatin and Enoxaparin Thromboprophylaxis Following Ovarian Cancer Surgery (O-STAT Study)

Study Overview
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Brief Summary
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This research study is studying a combination of two drug interventions called rosuvastatin and enoxaparin as a possible preventative measure against developing venous blood clots (such deep vein thrombosis or pulmonary embolism). . The drugs involved in this study are: Rosuvastatin, also known as Crestor Enoxaparin

Detailed Description
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This is a randomized pilot trial to estimate the effect of rosuvastatin on levels of tissue factor bearing microparticles (TFMP) in patients undergoing surgery for presumed ovarian cancer (including primary peritoneal and fallopian tube carcinoma). Women will either be randomized to enoxaparin subcutaneously once daily (Arm A) or enoxaparin in combination with rosuvastatin (Arm B). Arm C will receive thromboprophylaxis according to standard of care and not be randomized. Levels of circulating TFMP will be assessed in all patients on Day 1 and following surgery (days 15, 30 and day 60). A bilateral lower extremity ultrasound will be performed on days 30 and 60 for all participants to estimate the rate of VTE in the 3 arms.

Official Title
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Pilot Study of Rosuvastatin and Enoxaparin Thromboprophylaxis Following Ovarian Cancer Surgery (O-STAT Study)

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: Enoxaparin
* Drug: Enoxaparin + Rosuvastatin
* Other: Thromboprophylaxis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic diagnosis of ovarian, fallopian or primary peritoneal cancer (excluding borderline histologies). Preliminary pathology results based on frozen section findings are acceptable. The interval between pelvic or abdominal surgery and first dose of study treatment must be no more than 10 days. Age ≥ 18 years. ECOG performance status ≤2 (see Appendix A) Life expectancy of greater than 6 months Participants must have normal organ and marrow function as defined below: Platelets ≥ 100,000/mcL Total Bilirubin <1.5 mg/dL (or direct bilirubin <1.0 mg/dL) AST(SGOT) ≤ 1.5 × institutional upper limit of normal ALT(SGPT) ≤ 1.5 × institutional upper limit of normal Creatinine < 1.5 mg/dL OR Estimated creatinine clearance ≥60 mL/min/1.73 m2 The effects of rosuvastatin on the developing human fetus are unknown. For this reason and because statins used in this trial are thought to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Participants who are receiving any other investigational agents. Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and increased risk of intracranial hemorrhage History of allergic reactions attributed to compounds of similar chemical or biologic composition to enoxaparin or atorvastatin Active bleeding or high risk of bleeding (e.g. known acute gastrointestinal ulcer) History of heparin-induced thrombocytopenia. Any history of significant hemorrhage (requiring hospitalization or transfusion) outside of a surgical setting within the last year. Presence of coagulopathy defined as: PT > 1.3 x upper limit of normal PTT > 1.3 x upper limit of normal Uncontrolled hypothyroidism (defined as TSH below lower limit of normal). Qualifying TSH may be within 60 days prior to enrollment. If screening TSH is low, patients are eligible if free T4 is within normal limits. Familial bleeding diathesis Known diagnosis of disseminated intravascular coagulation Currently taking statin (i.e. rosuvastatin, atorvastatin, simvastatin) or fibrates Currently receiving anticoagulant therapy Current use of aspirin (>81 mg daily), Clopidogrel (Plavix), cilostazol (Pletal), aspirin-dipyridamole (Aggrenox). Known Asian descent (including Filipino, Chinese, Japanese, Korean, Vietnamese or Asian-Indian origin) due to altered metabolism of statins. Concomitant use of the following drugs: cyclosporine, fibrates, niacin, gemfibrozil, ketoconazole, spironolactone, cimetidine, warfarin, erythromycin, or protease inhibitors Known recent history of heavy alcohol use History of rhabdomyolysis while on statin therapy. Known active Hepatitis C or active Hepatitis B infection. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Pregnant women are excluded from this study due to the potential for teratogenic effects on the human fetus. Because there is an unknown but potential risk of adverse events in nursing infants secondary to the treatment of the mother with rosuvastatin, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomized to Arm Enoxaparin and Arm Enoxaparin + Rosuvastatin, and those requesting no randomization willl be directly assigned to Arm Standard-of-care Thromboprophylaxis
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enoxaparin<br>-Enoxaparin is administered subcutaneous daily | Drug: Enoxaparin<br>* Enoxaparin is used for prevention of blood clots following abdominal or orthopedic surgery and in medical patients with restricted mobility during acute illness<br>|
| Experimental: Enoxaparin + Rosuvastatin<br>Enoxaparin is administered subcutaneous daily. Rosuvastatin is administered daily orally starting on day 15 | Drug: Enoxaparin<br>* Enoxaparin is used for prevention of blood clots following abdominal or orthopedic surgery and in medical patients with restricted mobility during acute illness<br>Drug: Enoxaparin + Rosuvastatin<br>* Rosuvastatin is an anti-cholesterol medication that is FDA (the U.S. Food and Drug Administration) approved to lower cholesterol and reduce the risk of arterial blood clots. There is evidence that rosuvastatin can lower the risk of venous blood clots in healthy individuals Enoxaparin is used for prevention of blood clots following abdominal or orthopedic surgery and in medical patients with restricted mobility during acute illness<br>|
| Experimental: Thromboprophylaxis<br>-Thromboprophylaxis is administered per clinician discretion | Other: Thromboprophylaxis<br>* standard of care therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of differences in circulating tissue factor bearing microparticles between study arms | Concentration of tissue factor bearing microparticles | 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Point estimate of the rates of VTE following ovarian surgery in each study arm | VTE rate | 60 days | 
| Comparison of D-dimer values across study arms | D-dimer concentration | 60 days | 
| Compare the rates of VTE between study arms | VTE rate in arm A and B | 60 days | 
| Compare CRP between study arms | CRP concentration | 60 days | 
| Compare concentrations of TFMP, D-dimer, CRP at study timepoints. | Baseline vs day 60 comparison for TFMP, D-dimer, CRP on each arm | 60 days | 
| Assess incidence of major hemorrhage and clinically relevant bleeding as defined by the International Society of Thrombosis and Haemostasis | Major and clinically relevant non-major bleeding rates | 60 days | 
| Estimate the overall rate of any VTE | Overall VTE rates | 60 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ovarian Cancer