Clinical trial NCT03532139: Pilot Study of Rosuvastatin and Enoxaparin Thromboprophylaxis Following Ovarian Cancer Surgery (O-STAT Study)
Official title: Pilot Study of Rosuvastatin and Enoxaparin Thromboprophylaxis Following Ovarian Cancer Surgery (O-STAT Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: Ovarian Cancer
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2018-05-22
Enrollment: 24
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Comparison of differences in circulating tissue factor bearing microparticles between study arms
timeFrame: 60 days
Secondary outcomes:
measure: Point estimate of the rates of VTE following ovarian surgery in each study arm
timeFrame: 60 days
measure: Comparison of D-dimer values across study arms
timeFrame: 60 days
measure: Compare the rates of VTE between study arms
timeFrame: 60 days
measure: Compare CRP between study arms
timeFrame: 60 days
measure: Compare concentrations of TFMP, D-dimer, CRP at study timepoints.
timeFrame: 60 days
measure: Assess incidence of major hemorrhage and clinically relevant bleeding as defined by the International Society of Thrombosis and Haemostasis
timeFrame: 60 days
measure: Estimate the overall rate of any VTE
timeFrame: 60 days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Rushad Patell, MD
role: PRINCIPAL_INVESTIGATOR
References: