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

Data from clinical trials show that drugs called "statins", which is a family of drugs that
includes rosuvastatin, can prevent blood clotting in both cancer and non-cancer participants.
Rosuvastatin is currently approved by the FDA for the primary prevention of blood clotting in
the arteries of individuals without a history of cardiovascular disease.

With this trial, the investigators hope to determine if it is reasonable to conduct a study
in the future that determines the efficacy of blood clot prevention (prophylaxis) using
rosuvastatin in combination with enoxaparin following surgery for ovarian cancer.

Surgery and cancer are both known to increase the risk of blood clots. This study is being
conducted to determine if there are better ways to reduce this risk. This research study is a
Pilot Study, which is the first time investigators are examining how rosuvastatin in
combination with enoxaparin affect certain factors in the participant's blood, which have
been identified as having a link to increased risk of blood clotting.

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 but the FDA has not approved rosuvastatin for prevention of blood clots following
ovarian cancer surgery.

The FDA (the U.S. Food and Drug Administration) has approved enoxaparin for prevention of
blood clots following abdominal or orthopedic surgery and in medical patients with restricted
mobility during acute illness.

In this research study, the investigators are looking at differences between the levels of
certain small particles that are thought to cause blood clots (thrombosis) in participants
who receive a combination of rosuvastatin and enoxaparin compared with enoxaparin alone (or
standard of care therapy). A protein called tissue factor is commonly present on ovarian
cancer cells and cancer cells are thought to release particles in the blood containing tissue
factor. The levels of these particles circulating in the blood have been linked to an
increased risk of blood clots in people with cancer

Inclusion Criteria:

- Participants scheduled (or plan to schedule) for surgical resection of presumed
ovarian cancer (including fallopian tube cancer and primary peritoneal cancer)

- 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.

- Elevated creatine kinase >2 times the upper limit of normal

- Presence of coagulopathy defined as:

- PT > 1.3 x upper limit of normal

- PTT > 1.3 x upper limit of normal

- 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 history of 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.

- Participant must be able to swallow pills.

- 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.