Colorectal Metastasis Prevention International Trial 2

  • STATUS
    Recruiting
  • End date
    Feb 28, 2027
  • participants needed
    200
  • sponsor
    Assaf-Harofeh Medical Center
Updated on 23 January 2021
carcinoma
metastasis
rectal carcinoma

Summary

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

Details
Condition Colorectal Cancer, Rectal disorder, Colon Cancer Screening, Rectal Disorders, Colon cancer; rectal cancer, colorectal neoplasm, cancer, colorectal, colorectal tumor, tumors, colorectal
Treatment Placebo, Propranolol and Etodolac
Clinical Study IdentifierNCT03919461
SponsorAssaf-Harofeh Medical Center
Last Modified on23 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age between 20 yrs and 80 yrs?
Gender: Male or Female
Do you have Colorectal Cancer?
Do you have any of these conditions: Colon cancer; rectal cancer or Colorectal Cancer or colorectal tumor or colorectal neoplasm or tumors, colorectal or Colon Cancer Screening or Rectal ...?
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
\-

Exclusion Criteria

Patients with metastatic disease, known prior to surgery
Patients in whom surgical resection is planned without curative intent
Patients with renal failure, measured by creatinine level >1.5
Patients with significant heart failure (NYHA functional class 3 or higher)
Patients with significant liver failure (known cirrhosis, Bilirubin level>2)
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 antiinflammatory drug group or beta-blockers family
Patients treated chronically with any type of a beta-adrenergic blocker or a COX inhibitor
Patients with bradycardia or second or third degree AV block
Patients with a history of CVA/TIA
Patients with Printzmetal's angina
Patients with right sided heart failure owing to pulmonary hypertension
Patients with significant diagnosed cardiomegaly
Patients with (current) pheochromocytoma
Patients with chronic Digoxin treatment
Patients with active peptic disease
Pregnant women
Patients who participate in another interventional study
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
Patients with Immunodeficiency Disorders, or autoimmune disease treated by immunosuppressive medications
Patients suffering from sick sinus syndrome
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