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

NCT06839144 | Recruiting Phase 2 DMC

• 2 other identifiers: TLV-0199-241R21CA291683-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

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.

Conditions

Ovarian Cancer; Ovarian Cancer Metastatic Recurrent

Keywords

Ovarian Cancer; Perioperative Intervention; Beta-Blockers; Propranolol; COX-2 Inhibitors; Etodolac; Psychoneuroimmunology; Stress and Cancer; Randomized Controlled Trial (RCT); Biomarker Analysis

Outcome Measures

Primary Outcomes (5)

• Transcriptional Activity in Excised Tumors

  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

  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

  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

  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

  Number of participants enrolled in the study within the specified timeframe.

  Study duration (estimated 2 years).

Secondary Outcomes (1)

• Three-Year Recurrence Rate

  3 years post-surgery.

Study Arms (2)

Intervention Arm

EXPERIMENTAL

Patients receive propranolol + etodolac (active treatment)

Drug: Propranolol (Beta-Blocker) and Etodolac (COX-2 Inhibitor)

Placebo Arm

PLACEBO COMPARATOR

Patients receive matching placebo for both drugs

Drug: Placebo (Matching for Propranolol & Etodolac)

Interventions

Propranolol (Beta-Blocker) and Etodolac (COX-2 Inhibitor) DRUG

\- 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.

Intervention Arm

Placebo (Matching for Propranolol & Etodolac) DRUG

\- Placebo Arm: Placebo (Matching for Propranolol \& Etodolac). Inert placebo tablets matching propranolol and etodolac in appearance and dosing schedule. Administration Route: Oral.

Placebo Arm

Eligibility Criteria

• Age: 20 Years - 85 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Tel-Aviv Sourasky Medical Center: lead
• National Cancer Institute (NCI): collaborator
• The Chaim Sheba Medical Center: collaborator

Study Sites (2)

The Chaim Sheba Medical Center

Ramat Gan, 5266202, Israel

RECRUITING

Tel Aviv Sourasky Medical Center (Ichilov Hospital)

Tel Aviv, 6997801, Israel

RECRUITING

Related Publications (3)

• Shaashua L, Shabat-Simon M, Haldar R, Matzner P, Zmora O, Shabtai M, Sharon E, Allweis T, Barshack I, Hayman L, Arevalo J, Ma J, Horowitz M, Cole S, Ben-Eliyahu S. Perioperative COX-2 and beta-Adrenergic Blockade Improves Metastatic Biomarkers in Breast Cancer Patients in a Phase-II Randomized Trial. Clin Cancer Res. 2017 Aug 15;23(16):4651-4661. doi: 10.1158/1078-0432.CCR-17-0152. Epub 2017 May 10.

  PMID: 28490464 BACKGROUND

• Haldar R, Ricon-Becker I, Radin A, Gutman M, Cole SW, Zmora O, Ben-Eliyahu S. Perioperative COX2 and beta-adrenergic blockade improves biomarkers of tumor metastasis, immunity, and inflammation in colorectal cancer: A randomized controlled trial. Cancer. 2020 Sep 1;126(17):3991-4001. doi: 10.1002/cncr.32950. Epub 2020 Jun 13.

  PMID: 32533792 BACKGROUND

• Haldar R, Shaashua L, Lavon H, Lyons YA, Zmora O, Sharon E, Birnbaum Y, Allweis T, Sood AK, Barshack I, Cole S, Ben-Eliyahu S. Perioperative inhibition of beta-adrenergic and COX2 signaling in a clinical trial in breast cancer patients improves tumor Ki-67 expression, serum cytokine levels, and PBMCs transcriptome. Brain Behav Immun. 2018 Oct;73:294-309. doi: 10.1016/j.bbi.2018.05.014. Epub 2018 May 22.

  PMID: 29800703 BACKGROUND

MeSH Terms

Conditions

Ovarian Neoplasms; Neoplasms

Interventions

Propranolol; Adrenergic beta-Antagonists; Etodolac; Cyclooxygenase 2 Inhibitors

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Indoleacetic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Therapeutic Uses; Antirheumatic Agents

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shamgar Ben-Eliyahu, Prof.

CONTACT

972-3-6407266; shamgar@tauex.tau.ac.il

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2025
• First Posted: February 21, 2025
• Study Start: March 12, 2025
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: July 11, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Within 12 months of study completion and final data analysis.
• Access Criteria: Upon request via data-sharing agreements through Tel Aviv University.

Locations

IL (2)