Inhibiting Beta-adrenergic and COX-2 Signaling During the Perioperative Period to Reduce Ovarian Cancer Progression

Phase 2

Not yet recruiting

• Conditions: Ovarian Cancer; Ovarian Cancer Metastatic Recurrent
• Interventions: Drug: Propranolol (Beta-Blocker) and Etodolac (COX-2 Inhibitor); Drug: Placebo (Matching for Propranolol & Etodolac)

• Registration Number: NCT06839144
• Lead Sponsor: Tel-Aviv Sourasky Medical Center

Brief Summary

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.

Detailed 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.

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-06
• Study First Submitted QC: 2025-02-16
• Last Update Submitted: 2025-02-16
• Study First Posted: 2025-02-21
• Last Update Posted: 2025-02-21
• Study Start: 2025-02-28
• Primary Completion: 2027-02-28
• Study Completion: 2027-04-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention Arm	Propranolol (Beta-Blocker) and Etodolac (COX-2 Inhibitor)	Patients receive propranolol + etodolac (active treatment)
Placebo Arm	Placebo (Matching for Propranolol & Etodolac)	Patients receive matching placebo for both drugs

Primary Outcome Measures

Name	Time	Method
Transcriptional Activity in Excised Tumors	At the time of surgery (Day 0). Data will be reported through study completion, an average of 2 years.	Transcriptional activity related to pro-metastatic (e.g., EMT), pro-growth (STAT and GATA families), and stress and inflammatory signaling (NF-κB/cRel, AP-1, CREB, GR) in excised tumors.
Transcriptional Activity in Blood Samples	Preoperative baseline (Informed consent day), Day 0 (surgery), postoperative Day 1, Week 3, and Week 11. Data will be reported through study completion, an average of 2 years.	Longitudinal analysis of transcriptional activity in peripheral blood, focusing on stress/inflammatory pathways (NF-κB/cRel, AP-1, CREB, GR). Unit of measure: Relative expression levels (fold change).
Adverse Event Assessment	From 5 days pre-surgery to 3 months post-surgery.	Recording and categorization of adverse events, using a standardized tool (e.g., CTCAE-Common Terminology Criteria for Adverse Events) to assess the severity and type of adverse events. Unit of Measure: Number and severity of adverse events.
Patient Adherence to Drug Regimen	From 5 days pre-surgery to 3 months post-surgery.	Patient adherence will be assessed using pill counts or patient self-reports. Unit of Measure: Percentage of prescribed dosage consumed.
Recruitment Rate	Study duration (estimated 2 years).	Number of participants enrolled in the study within the specified timeframe.

Secondary Outcome Measures

Name	Time	Method
Three-Year Recurrence Rate	3 years post-surgery.	Assessment of recurrence in patients based on medical records and follow-ups at 3 years post-surgery.

Trial Locations

Locations (2)

The Chaim Sheba Medical Center; 🇮🇱 Ramat Gan, Israel

Tel Aviv Sourasky Medical Center (Ichilov Hospital); 🇮🇱 Tel Aviv, Israel