- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03919461
Colorectal Metastasis Prevention International Trial 2 (COMPIT-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
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Oded Zmora, MD
- Phone Number: +97289779202
- Email: ozmora@post.tau.ac.il
Study Locations
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-
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Afula, Israel, 1834111
- Not yet recruiting
- Haemek Medical Center
-
Contact:
- Doron Kopelman, MD
- Email: kopelman_d@clalit.org.il
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Haifa, Israel, 3109601
- Not yet recruiting
- Rambam Health Care Campus
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Contact:
- Simon D Duek, MD
- Email: d_duek@rambam.health.gov.il
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Petah-Tikva, Israel, 4941492
- Not yet recruiting
- Rabin Medical Center
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Contact:
- Nir Wasserberg, MD
- Email: nirw@clalit.org.il
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Tel Aviv, Israel, 6423906
- Not yet recruiting
- Sourasky Medical Center
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Contact:
- Hagit Tulchinsky, MD
- Email: hagitt@tlvmc.gov.il
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Tel HaShomer, Israel, 45858
- Not yet recruiting
- Sheba Medical Center
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Contact:
- Mordechai Gutman, MD
- Email: motti.gutman@sheba.health.gov.il
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Tsrifin, Israel, 70300
- Recruiting
- Asaf Harofeh Medical Center
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Contact:
- Oded Zmora, MD
- Phone Number: +97289779202
- Email: ozmora@post.tau.ac.il
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
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
-
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 anti- inflammatory 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- 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 20 days as follows.
Etodolac:400mg PO bid for the entire intervention period, Propranolol (slow release): 20 mg PO b.i.d. for 5 preoperative days; 80 mg PO b.i.d. on the day of surgery; 40 mg PO b.i.d. for the first post-operative week and 20 mg PO b.i.d. for the second post-operative week.
|
A perioperative combined drug regimen
Other Names:
|
Placebo Comparator: Placebo
Same schedule as in the active comparator arm
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Placebo
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
5-year disease-free-survival
Time Frame: From the date of surgery until malignant disease is identified, assessed up to 60 months post-surgery]
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Data regrading post-surgical recurrence will be recorded at 1,3,6,12,18,24,36,48, and 60 following surgery.
Primary outcome 1 will be rate of recurrence/disease at 60 months.
|
From the date of surgery until malignant disease is identified, assessed up to 60 months post-surgery]
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Biomarkers in extracted tumor tissue samples assessing pro- and anti-metastatic processes
Time Frame: An average of one year following surgery
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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
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An average of one year following surgery
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Biomarkers in blood samples assessing pro- and anti-metastatic processes
Time Frame: An average of one year following surgery
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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
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of patients with treatment related adverse events
Time Frame: 30 days following surgery
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According to the Clavien-Dindo classification system (7 grades of events depicting the severity of the event)
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30 days following surgery
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Depression, Anxiety, Global distress
Time Frame: At baseline and at 30 days post-surgery
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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
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Fatigue
Time Frame: At baseline and at 30 days post-surgery
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4 items related to fatigue in the 36 item short-form survey questionnaire.
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At baseline and at 30 days post-surgery
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Oded Zmora, MD, Asaf Harofeh Medical Center
Publications and helpful links
General Publications
- Haldar R, Shaashua L, Lavon H, Lyons YA, Zmora O, Sharon E, Birnbaum Y, Allweis T, Sood AK, Barshack I, Cole S, Ben-Eliyahu S. Perioperative inhibition of beta-adrenergic and COX2 signaling in a clinical trial in breast cancer patients improves tumor Ki-67 expression, serum cytokine levels, and PBMCs transcriptome. Brain Behav Immun. 2018 Oct;73:294-309. doi: 10.1016/j.bbi.2018.05.014. Epub 2018 May 22.
- Shaashua L, Shabat-Simon M, Haldar R, Matzner P, Zmora O, Shabtai M, Sharon E, Allweis T, Barshack I, Hayman L, Arevalo J, Ma J, Horowitz M, Cole S, Ben-Eliyahu S. Perioperative COX-2 and beta-Adrenergic Blockade Improves Metastatic Biomarkers in Breast Cancer Patients in a Phase-II Randomized Trial. Clin Cancer Res. 2017 Aug 15;23(16):4651-4661. doi: 10.1158/1078-0432.CCR-17-0152. Epub 2017 May 10.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Physiological Effects of Drugs
- Adrenergic beta-Antagonists
- Adrenergic Antagonists
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Antihypertensive Agents
- Vasodilator Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Cyclooxygenase Inhibitors
- Cyclooxygenase 2 Inhibitors
- Propranolol
- Etodolac
Other Study ID Numbers
- 0196-17-ASF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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