Inhibiting Beta-adrenergic and COX-2 Signaling During the Perioperative Period to Reduce Ovarian Cancer Progression: A Randomized Placebo-Controlled Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Transcriptional Activity in Excised Tumors
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 85 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
Intervention Arm
Patients receive propranolol + etodolac (active treatment)
干预措施: Propranolol (Beta-Blocker) and Etodolac (COX-2 Inhibitor) (Drug)
Placebo Arm
Patients receive matching placebo for both drugs
干预措施: Placebo (Matching for Propranolol & Etodolac) (Drug)
结局指标
主要结局
Transcriptional Activity in Excised Tumors
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: Study duration (estimated 2 years).
Number of participants enrolled in the study within the specified timeframe.
次要结局
- Three-Year Recurrence Rate(3 years post-surgery.)