Ovarian Cancer, Ovarian Cancer Metastatic Recurrent
Conditions
Keywords
Ovarian Cancer, Perioperative Intervention, Beta-Blockers, Propranolol, COX-2 Inhibitors, Etodolac, Psychoneuroimmunology, Stress and Cancer, Randomized Controlled Trial (RCT), Biomarker Analysis
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.
Interventions
DRUGPropranolol (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.
DRUGPlacebo (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.
Sponsors
National Cancer Institute (NCI)
The Chaim Sheba Medical Center
Tel-Aviv Sourasky Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Israel
Contacts
Primary ContactShamgar Ben-Eliyahu, Prof.
Outcome results
None listed