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Enoxaparin with or without Rosuvastatin Calcium in Preventing Blood Clots in Patients with Ovarian, Fallopian Tube, or Primary Peritoneal Cancer following Surgery

Trial Status: Active

This phase I trial studies how well with or without rosuvastatin calcium work in preventing blood clots in patients with ovarian, fallopian tube, or primary peritoneal cancer after surgery. Enoxaparin prevents blood clots. Rosuvastatin calcium is an anti-cholesterol medication that lowers cholesterol and may reduce the risk of arterial blood clots. Giving rosuvastatin calcium and enoxaparin may work better in preventing blood clots in patients with ovarian, fallopian tube, or primary peritoneal cancer following ovarian cancer surgery.

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
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 prior to surgery
  • Life expectancy of greater than 6 months
  • Adequate hematologic function on most recent post-operative test results defined as: Platelets >= 100,000/mcL
  • Adequate renal function on most recent post-operative test results defined as: Creatinine < 1.5 mg/dL or estimated creatinine clearance >= 60 mL/min/1.73 m^2
  • Total Bilirubin < 1.5 mg/dL (or direct bilirubin < 1.0 mg/dL)
  • Aspartate aminotransferases (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 1.5 x institutional upper limit of normal
  • Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x institutional upper limit of normal
  • 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 childbearing 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
  • Prothrombin time (PT) > 1.3 x upper limit of normal
  • Partial thromboplastin time (PTT) > 1.3 x upper limit of normal
  • Uncontrolled hypothyroidism (defined as thyroid stimulating hormone [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 thyroxine (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 therapeutic 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

Massachusetts

Boston
Beth Israel Deaconess Medical Center
Status: ACTIVE
Contact: Jeffrey Isaac Zwicker
Massachusetts General Hospital Cancer Center
Status: ACTIVE
Contact: Rachel Pam Greenberger Rosovsky

PRIMARY OBJECTIVE:

I. To evaluate whether rosuvastatin calcium (rosuvastatin) in combination with enoxaparin lowers levels of circulating TFMP compared with enoxaparin alone or standard-of-care thromboprophylaxis following laparotomy for ovarian cancer at 60 days.

SECONDARY OBJECTIVES:

I. Point estimate of the rates of venous thromboembolism (VTE) following ovarian surgery receiving enoxaparin alone (Arm A or Arm A+C) and enoxaparin with rosuvastatin (Arm B) at 15 and 60 days.

II. Comparison of D-dimer values at 30 and 60 days for enoxaparin/rosuvastatin (Arm B) with enoxaparin alone (Arm A) and/or standard of care (Arm C).

III. Compare the rates of VTE between study arms.

IV. Compare CRP between study arms.

V. Determine change in TFMP, D-dimer, CRP at day 60 compared with other time points.

VI. Evaluate factors that influence decision to forgo randomization (Arm C).

VII. Characterize size and cellular source of TFMP following surgery.

VIII. Assess whether measurement of tumor-derived microparticles correspond with the diagnosis, grade or stage of ovarian cancer.

IX. Assess incidence of major hemorrhage and clinically relevant bleeding as defined by the International Society of Thrombosis and Haemostasis.

X. Estimate the rate of asymptomatic proximal venous thromboembolic events, total VTE (including incidental, distal, or line-associated thrombosis), line-associated thrombosis.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive enoxaparin subcutaneously (SC) once daily (QD) on days 1-30 following surgery in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive enoxaparin SC QD on days 1-30 and rosuvastatin calcium orally (PO) QD on days 15-60 following surgery in the absence of disease progression or unacceptable toxicity.

ARM C (NON-RANDOMIZED): Patients receive standard of care.

Trial Phase Phase I

Trial Type Prevention

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
Jeffrey Isaac Zwicker

  • Primary ID 18-067
  • Secondary IDs NCI-2018-02314
  • Clinicaltrials.gov ID NCT03532139