Low Dose TamOxifen and LifestylE Changes for bReast cANcer prevenTion (TOLERANT)

March 13, 2024 updated by: European Institute of Oncology

Low Dose TamOxifen and LifestylE Changes for bReast cANcer prevenTion: a Randomized Phase II Biomarker Trial in Subjects at Increased Risk

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).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Women between 18 and 70 years old;

  2. 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

    > 5% breast cancer risk at 10 years, using the Tyrer Cuzick or the Breast Cancer Surveillance Consortium Risk models, or

    with previous diagnosis of intraepithelial neoplasia (surgery for ADH, LCIS, ER positive DCIS) within the last 3 years;

  3. Ability to understand and the willingness to sign a written informed consent document;
  4. 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;

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

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/or any current or past eating disorders;
  4. Any diagnosis of invasive neoplasia, except non-melanoma skin cancer, in the previous 5 years;
  5. 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);
  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 treatment cessation;
  9. Diabetes or any other clinical condition that at the investigator's discretion contraindicates the proposed intervention.
  10. No hormonal contraception is allowed during study intervention. Non-hormonal methods will be advised for women of childbearing potential (WOCBP)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Low dose tamoxifen
Tamoxifen 10 mg (1 tablet) every other day for 6 months.
Drug: Tamoxifen 10 mg Tablet
One tablet of Tamoxifen 10 mg every other day for 6 months
Other Names:
  • Low dose tamoxifen
Active Comparator: Low dose tamoxifen + Intermittent Caloric Restriction
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)
Other: Intermittent caloric restriction
"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)
Drug: Tamoxifen 10 mg Tablet
One tablet of Tamoxifen 10 mg every other day for 6 months
Other Names:
  • Low dose tamoxifen
Placebo Comparator: Lifestyle intervention
Step counter device
Behavioral: Step counter Device
Participants will receive personal advice on healthy lifestyle and a step counter
Active Comparator: Lifestyle Intervention + Intermittent Caloric Restriction
Step counter device + 5:2 diet (5 days/week at regular energy intake+2 days a week at an average 75% energy deficit)
Other: Intermittent caloric restriction
"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)
Behavioral: Step counter Device
Participants will receive personal advice on healthy lifestyle and a step counter

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Post intervention levels of circulating binding globulin
Time Frame: Through study completion, an average of 6 months
Sex hormone binding globulin level after 6 months of intervention
Through study completion, an average of 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Institute of Oncology

Collaborators

Istituto Oncologico Veneto IRCCS
Ente Ospedaliero Ospedali Galliera
Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale

Investigators

  • Principal Investigator: Bernardo Bonanni, MD, Istituto Europeo Di Oncologia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2024

Primary Completion (Estimated)

July 31, 2025

Study Completion (Estimated)

July 31, 2026

Study Registration Dates

First Submitted

August 23, 2023

First Submitted That Met QC Criteria

September 11, 2023

First Posted (Actual)

September 13, 2023

Study Record Updates

Last Update Posted (Actual)

March 15, 2024

Last Update Submitted That Met QC Criteria

March 13, 2024

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UID 3751
  • 2023-503994-39-00 (Other Identifier: EU CT number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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