Overview
This study investigates the impact of perioperative inhibition of beta-adrenergic and COX-2 signaling in ovarian cancer patients undergoing debulking surgery. The trial aims to assess the feasibility, safety, and biological effects of a combination of propranolol and etodolac in reducing cancer metastasis and improving immune responses.
Description
The study is a placebo-controlled randomized clinical trial (RCT) enrolling 60 women undergoing ovarian cancer debulking surgery. Participants will be assigned to receive propranolol (starting 5 days preoperatively, increased on the day of surgery, and continued postoperatively) and etodolac at a fixed dose. The primary outcomes include recruitment rate, drug safety, tolerability, adherence, and molecular tumor and blood characteristics. Secondary outcomes include 3-year recurrence rates.
Eligibility
Inclusion Criteria:
- Age 20-85
- ASA score 1-3 or ECOG Performance Status of 0 to 2
- Patients with a suspected high-grade ovarian epithelial cancer based on imaging, clinical examination, CA125, and/or tumor biopsy
- Patients planned for surgery for primary surgery, or interval debulking surgery for ovarian cancer
- Signed informed consent form
- Willing and able to comply with study procedures (physically and mentally)
Exclusion Criteria:
- Patients who participate in another interventional study
- Patients with known allergy to one or more of the study medications, or to any medication from the non-steroidal anti-inflammatory drug group or beta-blockers family
- Patients treated chronically with any type of a beta-adrenergic blocker or a COX inhibitor, except use of Aspirin, which will be discontinued at least 7 days prior to surgery, and until 3 weeks post-surgery
- Patients currently suffering from asthma (אסתמה פעילה בלבד), or required hospital admission or change in medical treatment for asthma within the past year
- Patients with active peptic disease
- Patients with a history of CVA/TIA
- Recent (within the last 5 years) or concurrent malignancies, with the exception of adequately treated in-situ carcinoma of the cervix or basal-cell carcinoma of the skin
- Patients with renal failure, measured by creatinine level >1.5
- Patients with significant liver dysfunction (known cirrhosis, Bilirubin level>2)
- Patients with significant heart failure (NYHA functional class 3 or Higher)
- Patients with bradycardia (heart rate of 50 or less) or second- or third-degree AV block
- Patients with right-sided heart failure owing to pulmonary hypertension
- Patients with chronic Digoxin treatment
- Patients with Printzmetal's angina
- Patients with significant diagnosed cardiomegaly
- Patients suffering from sick sinus syndrome
- Patients with peripheral vascular disease
- Patients with current (unresected) pheochromocytoma
- Pregnant women
- Patients who are treated with immunosuppressive medications, including chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial drug
- Patients with Immunodeficiency Disorders