Clinical trial NCT06839144: Inhibiting Beta-adrenergic and COX-2 Signaling During the Perioperative Period to Reduce Ovarian Cancer Progression
Official title: Inhibiting Beta-adrenergic and COX-2 Signaling During the Perioperative Period to Reduce Ovarian Cancer Progression: a Randomized Placebo-Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
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
Lead sponsor: Tel-Aviv Sourasky Medical Center
Sponsor class: OTHER_GOV
Collaborators: name: National Cancer Institute (NCI)
name: The Chaim Sheba Medical Center
First posted: 2025-02-21
Enrollment: 60
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Transcriptional Activity in Excised Tumors
timeFrame: At the time of surgery (Day 0). Data will be reported through study completion, an average of 2 years.
measure: Transcriptional Activity in Blood Samples
timeFrame: 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.
measure: Adverse Event Assessment
timeFrame: From 5 days pre-surgery to 3 months post-surgery.
measure: Patient Adherence to Drug Regimen
timeFrame: From 5 days pre-surgery to 3 months post-surgery.
measure: Recruitment Rate
timeFrame: Study duration (estimated 2 years).
Secondary outcomes:
measure: Three-Year Recurrence Rate
timeFrame: 3 years post-surgery.
Other outcomes:
Locations:
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center (Ichilov Hospital)
Study officials:
affiliation: Tel Aviv Sourasky Medical Center (Ichilov Hospital)
name: Nadav Michaan, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: The Chaim Sheba Medical Center (Tel Hashomer)
name: Anna Blecher, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Tel Aviv University
name: Shamgar Ben-Eliyahu, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.