Ignite Creation Date:
2025-12-24 @ 3:29 PM
Ignite Modification Date:
2025-12-26 @ 7:02 AM
Study NCT ID:
NCT06033092
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-08-28
First Post:
2023-08-23
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Low Dose TamOxifen and LifestylE Changes for bReast cANcer prevenTion
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D002285', 'term': 'Carcinoma, Intraductal, Noninfiltrating'}, {'id': 'D000071960', 'term': 'Breast Carcinoma In Situ'}], 'ancestors': [{'id': 'D000230', 'term': 'Adenocarcinoma'}, {'id': 'D002277', 'term': 'Carcinoma'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D002278', 'term': 'Carcinoma in Situ'}, {'id': 'D018299', 'term': 'Neoplasms, Ductal, Lobular, and Medullary'}, {'id': 'D001943', 'term': 'Breast Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D001941', 'term': 'Breast Diseases'}, {'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D013629', 'term': 'Tamoxifen'}, {'id': 'D013607', 'term': 'Tablets'}], 'ancestors': [{'id': 'D013267', 'term': 'Stilbenes'}, {'id': 'D001597', 'term': 'Benzylidene Compounds'}, {'id': 'D001555', 'term': 'Benzene Derivatives'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D004304', 'term': 'Dosage Forms'}, {'id': 'D004364', 'term': 'Pharmaceutical Preparations'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 200}}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2024-06-21', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-08', 'completionDateStruct': {'date': '2026-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-08-22', 'studyFirstSubmitDate': '2023-08-23', 'studyFirstSubmitQcDate': '2023-09-11', 'lastUpdatePostDateStruct': {'date': '2025-08-28', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2023-09-13', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-12', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Post intervention levels of circulating binding globulin', 'timeFrame': 'Through study completion, an average of 6 months', 'description': 'Sex hormone binding globulin level after 6 months of intervention'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Low Dose Tamoxifen', 'Intermittent Caloric Restriction', 'Sex Hormone Binding Globulin', 'Lifestyle'], 'conditions': ['BRCA Mutation', 'PALB2 Gene Mutation', 'Ductal Carcinoma in Situ', 'Lobular Carcinoma in Situ', 'ATM Gene Mutation', 'CHEK2 Gene Mutation', 'CDH1 Gene Mutation', 'RAD51C Gene Mutation', 'RAD51D Gene Mutation']}, 'referencesModule': {'references': [{'pmid': '39226292', 'type': 'DERIVED', 'citation': 'Guerrieri-Gonzaga A, Serrano D, Gnagnarella P, Johansson H, Zovato S, Nardi M, Pensabene M, Buccolo S, DeCensi A, Briata IM, Pistelli L, Sansone C, Mannucci S, Aristarco V, Macis D, Lazzeroni M, Aurilio G, Accornero CA, Gandini S, Bonanni B. Low dose TamOxifen and LifestylE changes for bReast cANcer prevention (TOLERANT study): Study protocol of a randomized phase II biomarker trial in women at increased risk for breast cancer. PLoS One. 2024 Sep 3;19(9):e0309511. doi: 10.1371/journal.pone.0309511. eCollection 2024.'}]}, 'descriptionModule': {'briefSummary': 'Circulating levels of Sex Hormone Binding Globulin (SHBG) are significantly associated with a decreased risk of breast cancer.\n\nThe main aim of this clinical trial is to verify whether Low Dose Tamoxifen (LDT) increases circulating levels of SHBG more than lifestyle intervention (LI) with or without intermittent caloric restriction (ICR) after 6 months in women at increased risk of breast cancer (i.e., healthy participants carriers of a germline pathogenic/likely pathogenetic variant in at least one of the following genes: BRCA1, BRCA2, PALB2, ATM, CHEK2, CDH1, RAD51C or RAD51D, or with \\> 5% breast cancer risk at 10 years, using the Tyrer Cuzick or the Breast Cancer Surveillance Consortium Risk models or with a recently resected intraepithelial neoplasia of the breast (IEN).\n\nThe secondary aims are:\n\n* to verify whether ICR significantly modulates primary and secondary endpoints such as Homeostasis Model Assessment (HOMA) index, immune and inflammatory markers, lipid profile, Adiponectin/Leptin (A/L) ratio, quality of life (QoL), Body mass index (BMI), fat body composition, safety and toxicity;\n* to verify whether LDT significantly modulates secondary endpoints, such as HOMA-index, immune and inflammatory markers, lipid profile, A/L ratio, QoL, BMI, fat body composition, safety and toxicity;\n* to investigate differences in microbiome composition by arms and the effect of changes in microbiome on QoL taking into account circulating biomarkers, cytokines, immune modulators, and inflammatory proteins in serum;\n* to investigate MD (Mammographic Breast Density) changes by LDT vs. LI, with or without ICR. This aim will be performed in a subgroup of participants (not all the participants will undergo mammography due to younger age).', 'detailedDescription': 'Italian, multicenter, phase II, biomarker trial. A total of 200 women aged 18-70 years will be randomly assigned (1:1:1:1) to one of the four intervention arms Arm 1: Low dose Tamoxifen (LDT) i.e. 10 mg every other day; Arm 2: Low dose Tamoxifen (LDT) + Intermittent Caloric Restriction (ICR); Arm 3: Lifestyle intervention (LI) using a step counter; Arm 4: Lifestyle intervention (LI) using a step counter + Intermittent Caloric Restriction (ICR).\n\nParticipants will be stratified by center and by disease status (high risk vs. previous IEN) and intervention will last six months for all arms.'}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '18 Years', 'genderBased': True, 'healthyVolunteers': True, 'eligibilityCriteria': "Inclusion Criteria:\n\n1. Women between 18 and 70 years old;\n2. Healthy participants carriers of a germline pathogenic/likely pathogenetic variant in at least one of the following genes BRCA1, BRCA2, PALB2, ATM, CHEK2, CDH1, RAD51C or RAD51D, or\n\n \\> 5% breast cancer risk at 10 years, using the Tyrer Cuzick or the Breast Cancer Surveillance Consortium Risk models, or\n\n with previous diagnosis of intraepithelial neoplasia (surgery for ADH, LCIS, ER positive DCIS) within the last 3 years;\n3. Ability to understand and the willingness to sign a written informed consent document;\n4. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1;\n\n5a. For high-risk strata: A negative mammogram or any radiological image based on age and center protocol screening within 6 months before baseline visit;\n\n5b. For IEN Strata: A negative mammogram within 12 months before baseline visit;\n\n6\\. A negative transvaginal ultrasound within 6 months before baseline visit.\n\nExclusion Criteria:\n\n1. Diagnosis of ER-negative (\\<10%) DCIS, or history of invasive breast cancer;\n2. Previous treatment with SERMs or any other hormonal treatment for breast neoplasms;\n3. BMI \\< 18.5 Kg/m2 and/or Malnutrition Universal Screening Tool (MUST) score ≥2 and/or any current or past eating disorders;\n4. Any diagnosis of invasive neoplasia, except non-melanoma skin cancer, in the previous 5 years;\n5. Any tamoxifen contraindications (abnormal liver function, previous ischemic heart disease, endometrial disorder, previous deep venous thrombosis, history of pulmonary embolus, current or suspected glaucoma, retinopathy and cataract);\n6. Current use of warfarin or other anticoagulant drugs\n7. Bilateral mastectomy;\n8. Pregnancy or desire to become pregnant in the subsequent 9 months after treatment cessation;\n9. Diabetes or any other clinical condition that at the investigator's discretion contraindicates the proposed intervention.\n10. No hormonal contraception is allowed during study intervention. Non-hormonal methods will be advised for women of childbearing potential (WOCBP)"}, 'identificationModule': {'nctId': 'NCT06033092', 'acronym': 'TOLERANT', 'briefTitle': 'Low Dose TamOxifen and LifestylE Changes for bReast cANcer prevenTion', 'organization': {'class': 'OTHER', 'fullName': 'European Institute of Oncology'}, 'officialTitle': 'Low Dose TamOxifen and LifestylE Changes for bReast cANcer prevenTion: a Randomized Phase II Biomarker Trial in Subjects at Increased Risk', 'orgStudyIdInfo': {'id': 'UID 3751'}, 'secondaryIdInfos': [{'id': '2023-503994-39-00', 'type': 'OTHER', 'domain': 'EU CT number'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Low dose tamoxifen', 'description': 'Tamoxifen 10 mg (1 tablet) every other day for 6 months.', 'interventionNames': ['Drug: Tamoxifen 10 mg Tablet']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Low dose tamoxifen + Intermittent Caloric Restriction', 'description': 'Tamoxifen 10 mg (1 tablet) every other day for 6 months + 5:2 diet (5 days/week at regular energy intake+2 days a week at an average 75% energy deficit)', 'interventionNames': ['Drug: Tamoxifen 10 mg Tablet', 'Other: Intermittent caloric restriction']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Lifestyle intervention', 'description': 'Step counter device', 'interventionNames': ['Behavioral: Step counter Device']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Lifestyle Intervention + Intermittent Caloric Restriction', 'description': 'Step counter device + 5:2 diet (5 days/week at regular energy intake+2 days a week at an average 75% energy deficit)', 'interventionNames': ['Other: Intermittent caloric restriction', 'Behavioral: Step counter Device']}], 'interventions': [{'name': 'Tamoxifen 10 mg Tablet', 'type': 'DRUG', 'otherNames': ['Low dose tamoxifen'], 'description': 'One tablet of Tamoxifen 10 mg every other day for 6 months', 'armGroupLabels': ['Low dose tamoxifen', 'Low dose tamoxifen + Intermittent Caloric Restriction']}, {'name': 'Intermittent caloric restriction', 'type': 'OTHER', 'description': '"5:2 diet": 5 days a week at regular energy intake and 2 days/week at 75% energy deficit (diet will be restricted at 500-800 kcal corresponding to a 75% reduction compared to normal size)', 'armGroupLabels': ['Lifestyle Intervention + Intermittent Caloric Restriction', 'Low dose tamoxifen + Intermittent Caloric Restriction']}, {'name': 'Step counter Device', 'type': 'BEHAVIORAL', 'description': 'Participants will receive personal advice on healthy lifestyle and a step counter', 'armGroupLabels': ['Lifestyle Intervention + Intermittent Caloric Restriction', 'Lifestyle intervention']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Genoa', 'country': 'Italy', 'facility': 'E.O. Galliera', 'geoPoint': {'lat': 44.40478, 'lon': 8.94439}}, {'zip': '20141', 'city': 'Milan', 'country': 'Italy', 'facility': 'Istituto Europeo di Oncologia', 'geoPoint': {'lat': 45.46427, 'lon': 9.18951}}, {'city': 'Napoli', 'country': 'Italy', 'facility': 'Istituto Nazionale Tumori G. Pascale', 'geoPoint': {'lat': 40.87618, 'lon': 14.5195}}, {'city': 'Padua', 'country': 'Italy', 'facility': 'Istituto Oncologico Veneto', 'geoPoint': {'lat': 45.40797, 'lon': 11.88586}}], 'overallOfficials': [{'name': 'Bernardo Bonanni, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Istituto Europeo di Oncologia'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'European Institute of Oncology', 'class': 'OTHER'}, 'collaborators': [{'name': 'Ente Ospedaliero Ospedali Galliera', 'class': 'OTHER'}, {'name': 'Istituto Oncologico Veneto IRCCS', 'class': 'OTHER'}, {'name': 'Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale', 'class': 'NETWORK'}], 'responsibleParty': {'type': 'SPONSOR'}}}}