Ignite Creation Date:
2025-12-24 @ 11:46 AM
Ignite Modification Date:
2026-01-06 @ 9:40 AM
Study NCT ID:
NCT03919461
Status:
RECRUITING
Last Update Posted:
2019-04-18
First Post:
2019-02-28
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Colorectal Metastasis Prevention International Trial 2
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015179', 'term': 'Colorectal Neoplasms'}], 'ancestors': [{'id': 'D007414', 'term': 'Intestinal Neoplasms'}, {'id': 'D005770', 'term': 'Gastrointestinal Neoplasms'}, {'id': 'D004067', 'term': 'Digestive System Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D005767', 'term': 'Gastrointestinal Diseases'}, {'id': 'D003108', 'term': 'Colonic Diseases'}, {'id': 'D007410', 'term': 'Intestinal Diseases'}, {'id': 'D012002', 'term': 'Rectal Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D011433', 'term': 'Propranolol'}, {'id': 'D017308', 'term': 'Etodolac'}], 'ancestors': [{'id': 'D050198', 'term': 'Phenoxypropanolamines'}, {'id': 'D011412', 'term': 'Propanolamines'}, {'id': 'D000605', 'term': 'Amino Alcohols'}, {'id': 'D000438', 'term': 'Alcohols'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D020005', 'term': 'Propanols'}, {'id': 'D000588', 'term': 'Amines'}, {'id': 'D009281', 'term': 'Naphthalenes'}, {'id': 'D011084', 'term': 'Polycyclic Aromatic Hydrocarbons'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D007210', 'term': 'Indoleacetic Acids'}, {'id': 'D000147', 'term': 'Acids, Heterocyclic'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D007211', 'term': 'Indoles'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 200}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2019-02-28', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-04', 'completionDateStruct': {'date': '2027-02-28', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2019-04-15', 'studyFirstSubmitDate': '2019-02-28', 'studyFirstSubmitQcDate': '2019-04-15', 'lastUpdatePostDateStruct': {'date': '2019-04-18', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2019-04-18', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-02-28', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': '5-year disease-free-survival', 'timeFrame': 'From the date of surgery until malignant disease is identified, assessed up to 60 months post-surgery]', 'description': '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.'}, {'measure': 'Biomarkers in extracted tumor tissue samples assessing pro- and anti-metastatic processes', 'timeFrame': 'An average of one year following surgery', 'description': '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'}, {'measure': 'Biomarkers in blood samples assessing pro- and anti-metastatic processes', 'timeFrame': 'An average of one year following surgery', 'description': '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)'}], 'secondaryOutcomes': [{'measure': 'Number of patients with treatment related adverse events', 'timeFrame': '30 days following surgery', 'description': 'According to the Clavien-Dindo classification system (7 grades of events depicting the severity of the event)'}, {'measure': 'Depression, Anxiety, Global distress', 'timeFrame': 'At baseline and at 30 days post-surgery', 'description': 'Assessed by changes on the brief symptom inventory 18 questionnaire (this questionnaire assess all three scales for depression, anxiety and global distress)'}, {'measure': 'Fatigue', 'timeFrame': 'At baseline and at 30 days post-surgery', 'description': '4 items related to fatigue in the 36 item short-form survey questionnaire.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Beta-blocker', 'Propranolol', 'COX-2 inhibitor', 'Etodolac'], 'conditions': ['Colorectal Neoplasms']}, 'referencesModule': {'references': [{'pmid': '29800703', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '28490464', 'type': 'BACKGROUND', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '20 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n1\\. 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\n\n\\-\n\nExclusion Criteria:\n\n1. Patients with metastatic disease, known prior to surgery\n2. Patients in whom surgical resection is planned without curative intent\n3. Patients with renal failure, measured by creatinine level \\>1.5\n4. Patients with significant heart failure (NYHA functional class 3 or higher)\n5. Patients with significant liver failure (known cirrhosis, Bilirubin level\\>2)\n6. Patients currently suffering from asthma or Chronic Obstructive Pulmonary Disease (COPD)\n7. Patients treated pharmacologically for diabetes mellitus (type 1/2),\n8. Patients with peripheral vascular disease\n9. Patients with known allergy to one or more of the study medications.\n10. Patients with known allergy to any medication from the non-steroidal anti- inflammatory drug group or beta-blockers family\n11. Patients treated chronically with any type of a beta-adrenergic blocker or a COX inhibitor\n12. Patients with bradycardia or second or third degree AV block\n13. Patients with a history of CVA/TIA\n14. Patients with Printzmetal's angina\n15. Patients with right sided heart failure owing to pulmonary hypertension\n16. Patients with significant diagnosed cardiomegaly\n17. Patients with (current) pheochromocytoma\n18. Patients with chronic Digoxin treatment\n19. Patients with active peptic disease\n20. Pregnant women\n21. Patients who participate in another interventional study\n22. Patients with history or concomitant malignant disease of any type (except for the current colon/rectal cancer)\n23. 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.\n24. Patients who are treated with immunosuppressive medications\n25. Patients with Immunodeficiency Disorders, or autoimmune disease treated by immunosuppressive medications.\n26. Patients suffering from sick sinus syndrome"}, 'identificationModule': {'nctId': 'NCT03919461', 'acronym': 'COMPIT-2', 'briefTitle': 'Colorectal Metastasis Prevention International Trial 2', 'organization': {'class': 'OTHER_GOV', 'fullName': 'Assaf-Harofeh Medical Center'}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': '0196-17-ASF'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Propranolol and etodolac', 'description': '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.', 'interventionNames': ['Drug: Propranolol and etodolac']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Same schedule as in the active comparator arm', 'interventionNames': ['Other: Placebo']}], 'interventions': [{'name': 'Propranolol and etodolac', 'type': 'DRUG', 'otherNames': ['Deralin and etopan'], 'description': 'A perioperative combined drug regimen', 'armGroupLabels': ['Propranolol and etodolac']}, {'name': 'Placebo', 'type': 'OTHER', 'description': 'Placebo', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '1834111', 'city': 'Afula', 'status': 'NOT_YET_RECRUITING', 'country': 'Israel', 'contacts': [{'name': 'Doron Kopelman, MD', 'role': 'CONTACT', 'email': 'kopelman_d@clalit.org.il'}], 'facility': 'HaEmek Medical Center', 'geoPoint': {'lat': 32.60907, 'lon': 35.2892}}, {'zip': '3109601', 'city': 'Haifa', 'status': 'NOT_YET_RECRUITING', 'country': 'Israel', 'contacts': [{'name': 'Simon D Duek, MD', 'role': 'CONTACT', 'email': 'd_duek@rambam.health.gov.il'}], 'facility': 'Rambam Health Care Campus', 'geoPoint': {'lat': 32.81303, 'lon': 34.99928}}, {'zip': '4941492', 'city': 'Petah Tikva', 'status': 'NOT_YET_RECRUITING', 'country': 'Israel', 'contacts': [{'name': 'Nir Wasserberg, MD', 'role': 'CONTACT', 'email': 'nirw@clalit.org.il'}], 'facility': 'Rabin Medical Center', 'geoPoint': {'lat': 32.08707, 'lon': 34.88747}}, {'zip': '6423906', 'city': 'Tel Aviv', 'status': 'NOT_YET_RECRUITING', 'country': 'Israel', 'contacts': [{'name': 'Hagit Tulchinsky, MD', 'role': 'CONTACT', 'email': 'hagitt@tlvmc.gov.il'}], 'facility': 'Sourasky Medical Center', 'geoPoint': {'lat': 32.08088, 'lon': 34.78057}}, {'zip': '45858', 'city': 'Tel Litwinsky', 'status': 'NOT_YET_RECRUITING', 'country': 'Israel', 'contacts': [{'name': 'Mordechai Gutman, MD', 'role': 'CONTACT', 'email': 'motti.gutman@sheba.health.gov.il'}], 'facility': 'Sheba Medical Center', 'geoPoint': {'lat': 32.05096, 'lon': 34.84588}}, {'zip': '70300', 'city': 'Ẕerifin', 'status': 'RECRUITING', 'country': 'Israel', 'contacts': [{'name': 'Oded Zmora, MD', 'role': 'CONTACT', 'email': 'ozmora@post.tau.ac.il', 'phone': '+97289779202'}], 'facility': 'Asaf Harofeh Medical Center', 'geoPoint': {'lat': 31.95731, 'lon': 34.84852}}], 'centralContacts': [{'name': 'Oded Zmora, MD', 'role': 'CONTACT', 'email': 'ozmora@post.tau.ac.il', 'phone': '+97289779202'}], 'overallOfficials': [{'name': 'Oded Zmora, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Asaf Harofeh Medical Center'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Assaf-Harofeh Medical Center', 'class': 'OTHER_GOV'}, 'collaborators': [{'name': 'Sheba Medical Center', 'class': 'OTHER_GOV'}, {'name': 'Rabin Medical Center', 'class': 'OTHER'}, {'name': 'Tel-Aviv Sourasky Medical Center', 'class': 'OTHER_GOV'}, {'name': 'Rambam Health Care Campus', 'class': 'OTHER'}, {'name': 'HaEmek Medical Center, Israel', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}