Low Dose TamOxifen and LifestylE Changes for bReast cANcer prevenTion

Last updated: June 28, 2024
Sponsor: European Institute of Oncology
Overall Status: Active - Recruiting

Phase

2

Condition

Carcinoma

Breast Cancer

Genitourinary Cancer

Treatment

Intermittent caloric restriction

Step counter Device

Tamoxifen 10 mg Tablet

Clinical Study ID

NCT06033092
UID 3751
2023-503994-39-00
  • Ages 18-70
  • Female
  • Accepts Healthy Volunteers

Study Summary

Circulating levels of Sex Hormone Binding Globulin (SHBG) are significantly associated with a decreased risk of breast cancer.

The 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).

The secondary aims are:

  • 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;

  • 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;

  • 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;

  • 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).

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Women between 18 and 70 years old;

  2. Healthy participants carriers of a germline pathogenic/likely pathogenetic variantin at least one of the following genes BRCA1, BRCA2, PALB2, ATM, CHEK2, CDH1, RAD51Cor RAD51D, or

> 5% breast cancer risk at 10 years, using the Tyrer Cuzick or the Breast CancerSurveillance Consortium Risk models, or with previous diagnosis of intraepithelial neoplasia (surgery for ADH, LCIS, ERpositive DCIS) within the last 3 years;

  1. Ability to understand and the willingness to sign a written informed consentdocument;

  2. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1;

5a. For high-risk strata: A negative mammogram or any radiological image based on age and center protocol screening within 6 months before baseline visit;

5b. For IEN Strata: A negative mammogram within 12 months before baseline visit;

  1. A negative transvaginal ultrasound within 6 months before baseline visit.

Exclusion

Exclusion Criteria:

  1. Diagnosis of ER-negative (<10%) DCIS, or history of invasive breast cancer;

  2. Previous treatment with SERMs or any other hormonal treatment for breast neoplasms;

  3. BMI < 18.5 Kg/m2 and/or Malnutrition Universal Screening Tool (MUST) score ≥2 and/orany current or past eating disorders;

  4. Any diagnosis of invasive neoplasia, except non-melanoma skin cancer, in theprevious 5 years;

  5. Any tamoxifen contraindications (abnormal liver function, previous ischemic heartdisease, endometrial disorder, previous deep venous thrombosis, history of pulmonaryembolus, current or suspected glaucoma, retinopathy and cataract);

  6. Current use of warfarin or other anticoagulant drugs

  7. Bilateral mastectomy;

  8. Pregnancy or desire to become pregnant in the subsequent 9 months after treatmentcessation;

  9. Diabetes or any other clinical condition that at the investigator's discretioncontraindicates the proposed intervention.

  10. No hormonal contraception is allowed during study intervention. Non-hormonal methodswill be advised for women of childbearing potential (WOCBP)

Study Design

Total Participants: 200
Treatment Group(s): 4
Primary Treatment: Intermittent caloric restriction
Phase: 2
Study Start date:
June 21, 2024
Estimated Completion Date:
January 31, 2026

Study Description

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).

Participants will be stratified by center and by disease status (high risk vs. previous IEN) and intervention will last six months for all arms.

Connect with a study center

  • E.O. Galliera

    Genoa,
    Italy

    Site Not Available

  • Istituto Europeo di Oncologia

    Milan, 20141
    Italy

    Site Not Available

  • Istituto Nazionale Tumori G. Pascale

    Napoli,
    Italy

    Site Not Available

  • Istituto Oncologico Veneto

    Padova,
    Italy

    Active - Recruiting

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