Ignite Creation Date:
2025-12-24 @ 2:00 PM
Ignite Modification Date:
2026-02-22 @ 9:39 AM
Study NCT ID:
NCT02042495
Status:
WITHDRAWN
Last Update Posted:
2016-08-30
First Post:
2014-01-12
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Endometrial Cancer Biomarker Changes Following Exposure to Metformin
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D016889', 'term': 'Endometrial Neoplasms'}], 'ancestors': [{'id': 'D014594', 'term': 'Uterine Neoplasms'}, {'id': 'D005833', 'term': 'Genital Neoplasms, Female'}, {'id': 'D014565', 'term': 'Urogenital Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D014591', 'term': 'Uterine Diseases'}, {'id': 'D005831', 'term': 'Genital Diseases, Female'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D000091662', 'term': 'Genital Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D008687', 'term': 'Metformin'}], 'ancestors': [{'id': 'D001645', 'term': 'Biguanides'}, {'id': 'D006146', 'term': 'Guanidines'}, {'id': 'D000578', 'term': 'Amidines'}, {'id': 'D009930', 'term': 'Organic Chemicals'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 0}}, 'statusModule': {'whyStopped': 'Did not obtain Health Canda approval for drug use in reasonable time and moved onward to new trial', 'overallStatus': 'WITHDRAWN', 'startDateStruct': {'date': '2016-08'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2016-08', 'lastUpdateSubmitDate': '2016-08-29', 'studyFirstSubmitDate': '2014-01-12', 'studyFirstSubmitQcDate': '2014-01-19', 'lastUpdatePostDateStruct': {'date': '2016-08-30', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2014-01-23', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2017-12', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change in phosphorylated-S6', 'timeFrame': '4-6 weeks', 'description': 'Paired-t test will be used to determine the effect of oral metformin on the phosphorylated-S6 in pre-treatment and post-treatment endometrial samples.'}], 'secondaryOutcomes': [{'measure': 'Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing Ki-67', 'timeFrame': '4-6 weeks', 'description': 'Additional biomarker tested:\n\n* Ki-67'}, {'measure': 'Assess each patients insulin resistive state using the HOMA (homeostatic model assessment) index', 'timeFrame': '4-6 weeks', 'description': 'Assess the effect of metformin on pre-treatment and post-treatment biomarkers in serum to determine the HOMA index\n\n* fasting IGF-I\n* fasting insulin\n* fasting IGFBP-1\n* fasting glucose levels'}, {'measure': 'Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing the TUNEL assay', 'timeFrame': '4-6 weeks', 'description': 'Additional biomarker tested:\n\n* TUNEL assay for apoptosis level'}, {'measure': 'Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated AMPK', 'timeFrame': '4-6 weeks', 'description': 'Additional biomarker tested:\n\n* phosphorylated-AMPK'}, {'measure': 'Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated IGF-1R', 'timeFrame': '4-6 weeks', 'description': 'Additional biomarker tested:\n\n* phosphorylated-IGF-1R'}, {'measure': 'Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated insulin-receptor substrate protein 1 (phosphor-IRS1)', 'timeFrame': '4-6 weeks', 'description': 'Additional biomarker tested:\n\n* phosphor-IRS1'}, {'measure': 'Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated-Akt', 'timeFrame': '4-6 weeks', 'description': 'Additional biomarker tested:\n\n* phospho-Akt'}, {'measure': 'Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated mTOR', 'timeFrame': '4-6 weeks', 'description': 'Additional biomarker tested:\n\n* phosphor-mTOR'}, {'measure': 'Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated acetyl-CoA carboxylase (pACC)', 'timeFrame': '4-6 weeks', 'description': 'Additional biomarker tested:\n\n* pACC'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'conditions': ['Endometrial Cancer']}, 'descriptionModule': {'briefSummary': 'The investigators will explore the chemopreventive role of metformin. The purpose of this study is to determine whether, among patients with endometrial cancer, treatment with the currently approved insulin sensitizing drug metformin increases or decreases pathway activation distal to the insulin receptor in endometrial cancer tissue. This is a phase IIa study of metformin to be used to the pre-operative period of women diagnosed with endometrial cancer by comparing their endometrial biopsy specimens taken at their initial visit and after 4-6 weeks of treatment of metformin on the day of their surgical staging.', 'detailedDescription': 'Aim 1 To determine whether, among patients with endometrial cancer, treatment with the currently approved insulin sensitizing drug metformin increases or decreases pathway activation distal to the insulin receptor in endometrial cancer tissue.\n\nAim II To compare specified biomarkers in each endometrial cancer patient before and after receiving metformin. Our goal is to compare the following biomarkers in each patient before and after metformin administration: Ki-67, TUNEL assay for apoptosis level, phosphor-AMPK, phosphor-IGF-1R, phosphor-IRS1, phospho-Akt, phospho-S6, phosphor-mTOR, pACC.\n\nAll patients diagnosed with endometrial cancer presenting to the Jewish General Hospital for surgical treatment will be invited to participate.'}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Have a confirmed diagnosis of endometrial cancer based on an endometrial sampling though biopsy or dilatation and curettage\n* Must be able to undergo appropriate surgical staging for endometrial cancer\n* Must consent to be in the study and must have signed and dated an IRB-approved consent form conforming to government and institutional guidelines\n\nExclusion Criteria:\n\n* Patients with a contraindication to receiving metformin treatment\n* Patients with cognitive impairment\n* Renal or hepatic functioning \\> 125% upper limit of normal\n* Currently on medications for metabolic diseases, such as diabetes mellitus\n* History of lactic acidosis\n* Treatment with medications that may increase metformin levels: cationic drugs, e.g., digoxin, amiloride, procainamide, trimethoprim, vancomycin, triamterene, and morphine\n* History of chronic alcohol abuse'}, 'identificationModule': {'nctId': 'NCT02042495', 'briefTitle': 'Endometrial Cancer Biomarker Changes Following Exposure to Metformin', 'organization': {'class': 'OTHER', 'fullName': 'Jewish General Hospital'}, 'officialTitle': 'A Clinical Trial to Evaluate Endometrial Cancer Biomarker Changes Following Exposure to the Insulin Sensitizer Metformin', 'orgStudyIdInfo': {'id': 'JGH-140111'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Metformin', 'description': 'Metformin 500 mg PO TID from time of entry to study until scheduled surgical staging operation.\n\nIn cases of unresolving side effects, the metformin will be dose reduced to metformin 500 mg PO BID with evaluation after 1 week followed by withdrawal from the study if side effects persist.', 'interventionNames': ['Drug: Metformin']}], 'interventions': [{'name': 'Metformin', 'type': 'DRUG', 'otherNames': ['glucophage'], 'armGroupLabels': ['Metformin']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'H3T1E2', 'city': 'Montreal', 'state': 'Quebec', 'country': 'Canada', 'facility': 'Jewish General Hospital', 'geoPoint': {'lat': 45.50884, 'lon': -73.58781}}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Jewish General Hospital', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'MD, MSc, FRCSC', 'investigatorFullName': 'Shannon Salvador', 'investigatorAffiliation': 'Jewish General Hospital'}}}}