Inhibiting Beta-adrenergic and COX-2 Signaling During the Perioperative Period to Reduce Ovarian Cancer Progression (OC-POP-PT)

July 8, 2025 updated by: Tel-Aviv Sourasky Medical Center

Inhibiting Beta-adrenergic and COX-2 Signaling During the Perioperative Period to Reduce Ovarian Cancer Progression: A Randomized Placebo-Controlled Clinical Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Israel
      • Ramat Gan, Israel, 5266202
      • Tel Aviv, Israel, 6997801
        • Recruiting
        • Tel Aviv Sourasky Medical Center (Ichilov Hospital)
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention Arm
Patients receive propranolol + etodolac (active treatment)
Drug: Propranolol (Beta-Blocker) and Etodolac (COX-2 Inhibitor)

- Intervention Arm: Propranolol (Beta-Blocker) and Etodolac (COX-2 Inhibitor). Name: Propranolol (slow-Release) and Etodolac.

Propranolol Dosage Schedule:

5 days pre-surgery: 20mg twice daily (BID), Day of surgery: 80mg BID,

1-week Post-surgery: 40mg BID, week 2-11 post-surgery: 20mg BID.

Etodolac Dosage Schedule:

5 days pre-surgery until 3 weeks post-surgery: 400mg BID.

Administration Route: Oral.
Placebo Comparator: Placebo Arm
Patients receive matching placebo for both drugs
Drug: Placebo (Matching for Propranolol & Etodolac)
- Placebo Arm: Placebo (Matching for Propranolol & Etodolac). Inert placebo tablets matching propranolol and etodolac in appearance and dosing schedule. Administration Route: Oral.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Transcriptional Activity in Excised Tumors
Time Frame: 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.
At the time of surgery (Day 0). Data will be reported through study completion, an average of 2 years.
Transcriptional Activity in Blood Samples
Time Frame: 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).
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.
Adverse Event Assessment
Time Frame: 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.
From 5 days pre-surgery to 3 months post-surgery.
Patient Adherence to Drug Regimen
Time Frame: 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.
From 5 days pre-surgery to 3 months post-surgery.
Recruitment Rate
Time Frame: Study duration (estimated 2 years).
Number of participants enrolled in the study within the specified timeframe.
Study duration (estimated 2 years).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Three-Year Recurrence Rate
Time Frame: 3 years post-surgery.
Assessment of recurrence in patients based on medical records and follow-ups at 3 years post-surgery.
3 years post-surgery.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tel-Aviv Sourasky Medical Center

Collaborators

National Cancer Institute (NCI)
The Chaim Sheba Medical Center

Investigators

  • Principal Investigator: Nadav Michaan, Prof., Tel Aviv Sourasky Medical Center (Ichilov Hospital)
  • Principal Investigator: Anna Blecher, Dr., The Chaim Sheba Medical Center (Tel Hashomer)
  • Principal Investigator: Shamgar Ben-Eliyahu, Prof., Tel Aviv University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 12, 2025

Primary Completion (Estimated)

August 31, 2026

Study Completion (Estimated)

August 31, 2026

Study Registration Dates

First Submitted

February 6, 2025

First Submitted That Met QC Criteria

February 16, 2025

First Posted (Actual)

February 21, 2025

Study Record Updates

Last Update Posted (Actual)

July 11, 2025

Last Update Submitted That Met QC Criteria

July 8, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TLV-0199-24
  • 1R21CA291683-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Time Frame

Within 12 months of study completion and final data analysis.

IPD Sharing Access Criteria

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

IPD Sharing Supporting Information Type

  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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