2019-11-20
2026-01
2026-01
210
NCT03838029
Assaf-Harofeh Medical Center
Assaf-Harofeh Medical Center
INTERVENTIONAL
Perioperative Intervention to Reduce Metastatic Processes in Pancreatic Cancer Patients Undergoing Curative Surgery
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.
N/A
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Registration Dates | Results Reporting Dates | Study Record Updates |
---|---|---|
2019-01-23 | N/A | 2019-11-19 |
2019-02-11 | N/A | 2019-11-20 |
2019-02-12 | N/A | 2019-11 |
This section provides details of the study plan, including how the study is designed and what the study is measuring.
Primary Purpose:
Prevention
Allocation:
Randomized
Interventional Model:
Parallel
Masking:
Quadruple
Arms and Interventions
Participant Group/Arm | Intervention/Treatment |
---|---|
ACTIVE_COMPARATOR: Propranolol and etodolac Both study medications will be given orally for an intervention phase of 35 days as follows. Etodolac:400mg PO bid for the entire intervention period,Propranolol:20 mg PO bid for 5 preoperative days, 80 mg PO bid on the day of surgery and the following mo | DRUG: Propranolol and etodolac
|
PLACEBO_COMPARATOR: Placebo Same schedule as in the active comparator arm | OTHER: Placebo
|
Primary Outcome Measures | Measure Description | Time Frame |
---|---|---|
Rate of cancer recurrence | Data regrading post-surgical recurrence will be recorded at 1,3,6,12,18,24,36,48, and 60 following surgery | From the date of surgery until malignant disease is identified, assessed up to 60 months post-surgery |
Biomarkers in extracted tumor tissue samples | Epithelial-to-mesenchymal-transition ( EMT) status and natural-killer cell, macrophage, T-cell, and B-cell infiltration levels into tumor tissue (as assessed by messenger RNA profiling of tissue samples. | An average of one year following surgery |
Biomarkers in blood samples | Cytokine levels in blood samples (interleukin-6, interleukin-10, C-reactive protein, interferon-gamma, and vascular endothelial growth factor and additional exploratory analysis of other cytokines) | An average of one year following surgery |
Secondary Outcome Measures | Measure Description | Time Frame |
---|---|---|
Number of patients with treatment related adverse events | According to the Clavien-Dindo classification system (7 grades of events depicting the severity of the event) | 30 days following surgery |
Depression, Anxiety, Global distress | Assessed by changes on the brief symptom inventory 18 questionnaire (this questionnaire assess all three scales for depression, anxiety and global distress) | At baseline and at 30 days post-surgery |
Fatigue | 4 items related to fatigue in the 36 item short-form survey questionnaire. | At baseline and at 30 days post-surgery |
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact Name: Oded Zmora, MD Phone Number: +97289779202 Email: ozmora@post.tau.ac.il |
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.
Ages Eligible for Study:
ALL
Sexes Eligible for Study:
20 Years
Accepts Healthy Volunteers:
This is where you will find people and organizations involved with this study.
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
NPCF was founded on May 29, 2009 and is a 501(c)(3) organization. All donations are tax deductible.
The information and services provided by the National Pancreatic Cancer Foundation are for informational purposes only. The information and services are not intended to be substitutes for professional medical advice, diagnosis or treatment. The National Pancreatic Cancer Foundation does not recommend nor endorse any specific physicians, products or treatments even though they may be mentioned on this site.