Colorectal Metastasis Prevention International Trial 2
Status:
Recruiting
Trial end date:
2027-02-28
Target enrollment:
Participant gender:
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
Phase:
Phase 2
Details
Lead Sponsor:
Assaf-Harofeh Medical Center
Collaborators:
HaEmek Medical Center, Israel Rabin Medical Center Rambam Health Care Campus Sheba Medical Center Tel-Aviv Sourasky Medical Center