NCT03919461RecruitingPhase 2
Colorectal Metastasis Prevention International Trial 2
Perioperative Use of a β-adrenergic Blocker, Propranolol, and a COX2 Inhibitor, Etodolac, in Patients Undergoing Resection With Curative Intent for Primary Colon and Rectal Cancer: Effect on Tumor Recurrence and Survival
Source: ClinicalTrials.gov · Last updated 18 Apr 2019 · Not updated for over 12 months - ask the site whether it is still open
Brief summary (registry, in English)
The short perioperative period (days to weeks around surgery) is characterized by stress-inflammatory responses, including catecholamines (CAs, e.g., adrenaline) and prostaglandins (PGs, e.g., prostaglandin-E2) release, and induce deleterious pro-metastatic effects. Animal studies implicated excess perioperative release of CAs and PGs in facilitating cancer progression by affecting the malignant tissue, its local environment, and anti-metastatic immune functions. Congruently, animal studies conducted by the investigators indicate that combined use of the beta-adrenergic blocker, propranolol, and the prostaglandins inhibitor, etodolac - but neither drug separately - efficiently prevented post-operative metastatic development. Two recently conducted clinical trials, conducted by the investigators, in three medical centers in Israel, recruiting breast (n=38) and colorectal (n=34) cancer patients, assessing the safety and short-term efficacy of perioperative propranolol and etodolac treatment. Drugs were well tolerated, without severe adverse events. Importantly, molecular/biological analyses of the excised primary tumor indicated that drug treatment caused promising anti-metastatic transformations, as well as improvements in immune and inflammatory indices. These included (i) decreased tumor cell capacity to migrate, (ii) reduced pro-metastatic capacity of the malignant tissue, and (iii) improvement in immune infiltrating into the tumor (Paper published in Clinical Cancer Research, 2017). Herein, the investigators propose to conduct a double-blind placebo-controlled two-arm Phase II clinical trial in 200 colorectal cancer patients undergoing curative surgery in Israel. A perioperative 20-day drug treatment will be initiated 5 days before surgery. Primary outcomes will include (i) 3-year disease-free-survival (DFS), and 5-year overall survival (OS); and (ii) biological markers in blood samples, and in the excised tumor tissue. Secondary outcomes will include safety indices and psychological measures of depression, anxiety, distress, and fatigue
- Status (registry)
- Recruiting
- Phase (registry)
- Phase 2
- Study type
- Interventional
- Enrollment
- 200 (estimated)
- First submitted
- 28 Feb 2019
- Start date
- 28 Feb 2019
- Primary completion date
- 28 Feb 2027
- Lead sponsor
- Assaf-Harofeh Medical Center
- Diseases
- Colorectal cancer
- NCT number
- NCT03919461
What you commit to
- Study type: Interventional · Phase 2
- Planned participants: 200
- From 28 Feb 2019 to the primary completion date, 28 Feb 2027
- 6 sites in 1 country
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Prior treatment
- Patients with metastatic disease, known prior to surgery
- Patients in whom surgical resection is planned without curative intent
- Patients treated chronically with any type of a beta-adrenergic blocker or a COX inhibitor
- Patients with history or concomitant malignant disease of any type (except for the current colon/rectal cancer)
- Patients who were treated with chemotherapy in the last 10 years for any reason besides neo-adjuvant therapy for rectal cancer within the last six months.
- Patients who are treated with immunosuppressive medications
Other illness
- Patients with significant heart failure (NYHA functional class 3 or higher)
- Patients currently suffering from asthma or Chronic Obstructive Pulmonary Disease (COPD)
- Patients treated pharmacologically for diabetes mellitus (type 1/2),
- Patients with peripheral vascular disease
- Patients with known allergy to one or more of the study medications.
- Patients with known allergy to any medication from the non-steroidal anti- inflammatory drug group or beta-blockers family
- Patients with a history of CVA/TIA
- Patients with Printzmetal's angina
- Patients with right sided heart failure owing to pulmonary hypertension
- Patients with active peptic disease
- Patients with Immunodeficiency Disorders, or autoimmune disease treated by immunosuppressive medications.
- Patients suffering from sick sinus syndrome
Lab values
- Patients with renal failure, measured by creatinine level \>1.5
- Patients with significant liver failure (known cirrhosis, Bilirubin level\>2)
Other
- Patients with bradycardia or second or third degree AV block
- Patients with significant diagnosed cardiomegaly
- Patients with (current) pheochromocytoma
- Patients with chronic Digoxin treatment
- Pregnant women
- Patients who participate in another interventional study
Who the study is looking for
- 1\. Patients planned for surgery for primary resection of colon or rectal cancer with curative intent. 2. Single colonic or rectal carcinoma, proven by full colonoscopy and tumor biopsy. 3. No evidence of metastatic disease prior to surgery. Minimal workup would include abdominal CT with IV contrast (or CT+liver US) and chest XR. 4. ASA score of 1-3 or ECOG Performance Status of 0 to 1 5. Signed informed consent form 6. Willing and able to comply with study procedures (physically and mentally) 7. Men and women from age 20 to age 80
- \-
Age in the registry: 20 years to 80 years · Sex: All · Does not accept healthy volunteers
Sites (6)
Sites in registry order. Pick your city on the disease page to sort them by distance.
| Site | City | Country | Site status |
|---|---|---|---|
| Haemek Medical Center Coordinator of this site? Confirm its status | Afula | Israel | Not yet recruiting |
| Rambam Health Care Campus Coordinator of this site? Confirm its status | Haifa | Israel | Not yet recruiting |
| Rabin Medical Center Coordinator of this site? Confirm its status | Petah Tikva | Israel | Not yet recruiting |
| Sourasky Medical Center Coordinator of this site? Confirm its status | Tel Aviv | Israel | Not yet recruiting |
| Sheba medical center Coordinator of this site? Confirm its status | Tel HaShomer | Israel | Not yet recruiting |
| Asaf Harofeh Medical Center Coordinator of this site? Confirm its status | Tsrifin | Israel | Recruiting |
Related publications
- Favorable safety outcomes of a perioperative propranolol and etodolac regimen in cancer patients in four randomized controlled trials.Front Pharmacol · 2026 · PMID 42088573
This page is information, not medical advice. Discuss any trial with your doctor.