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.

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.

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

Within 12 months of study completion and final data analysis.

Upon request via data-sharing agreements through Tel Aviv University.