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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
60
\- 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 Arm: Placebo (Matching for Propranolol \& Etodolac). Inert placebo tablets matching propranolol and etodolac in appearance and dosing schedule. Administration Route: Oral.
The Chaim Sheba Medical Center
Ramat Gan, Israel
RECRUITINGTel Aviv Sourasky Medical Center (Ichilov Hospital)
Tel Aviv, Israel
RECRUITINGTranscriptional 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.
Time frame: 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).
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.
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.
Time frame: 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.
Time frame: From 5 days pre-surgery to 3 months post-surgery.
Recruitment Rate
Number of participants enrolled in the study within the specified timeframe.
Time frame: Study duration (estimated 2 years).
Three-Year Recurrence Rate
Assessment of recurrence in patients based on medical records and follow-ups at 3 years post-surgery.
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Time frame: 3 years post-surgery.