Perioperative Intervention to Reduce Metastatic Processes in Pancreatic Cancer Patients Undergoing Curative Surgery
Status:
Recruiting
Trial end date:
2026-01-01
Target enrollment:
Participant gender:
Summary
In Israel, of the ~1000 patients diagnosed annually with pancreatic cancer (PC),
approximately 250 (25 percent) will be eligible for curative surgery, of which 80 percent
will succumb to post-surgical metastatic disease. A reduction in post-surgical metastatic
disease will save dozens of patients in Israel annually, and tens-of thousands-around the
world. 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, our animal studies 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. We
recently conducted two clinical trials 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, we propose to conduct a double-blind placebo-controlled two-arm
Phase II clinical trial in 210 pancreatic cancer patients undergoing curative surgery in
Israel. A perioperative 35-day drug treatment will be initiated 5 days before surgery.
Primary outcomes will include (i) 1-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.