BRCA MutationPhase 2TOLERANTNCT06033092
Low Dose TamOxifen and LifestylE Changes for bReast cANcer prevenTion
A Phase 2 study testing Tamoxifen 10 mg Tablet, Intermittent caloric restriction and Step counter Device in people with BRCA Mutation and PALB2 Gene Mutation, run by European Institute of Oncology at 4 sites in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- BRCA Mutation, PALB2 Gene Mutation, Ductal Carcinoma in Situ
- What is being tested?
- Tamoxifen 10 mg Tablet, Intermittent caloric restriction and Step counter Device
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 110 participants
- Where
- 4 sitesItaly
- Study dates
- 21 Jun 2024to 31 Jul 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Women between 18 and 70 years old;
- 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;
- Ability to understand and the willingness to sign a written informed consent document;
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1;
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- 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.
Who cannot join
- Diagnosis of ER-negative (<10%) DCIS, or history of invasive breast cancer;
- Previous treatment with SERMs or any other hormonal treatment for breast neoplasms;
- BMI < 18.5 Kg/m2 and/or Malnutrition Universal Screening Tool (MUST) score ≥2 and/or any current or past eating disorders;
- Any diagnosis of invasive neoplasia, except non-melanoma skin cancer, in the previous 5 years;
- 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);
- Current use of warfarin or other anticoagulant drugs
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- Bilateral mastectomy;
- Pregnancy or desire to become pregnant in the subsequent 9 months after treatment cessation;
- Diabetes or any other clinical condition that at the investigator's discretion contraindicates the proposed intervention.
- No hormonal contraception is allowed during study intervention. Non-hormonal methods will be advised for women of childbearing potential (WOCBP)
Trial locations and contacts
4 sites in 1 country.
Italy4 sites
E.O. Galliera
Genoa
Istituto Europeo di Oncologia
Milan, 20141
Istituto Nazionale Tumori G. Pascale
Naples
Istituto Oncologico Veneto
Padova
About this study
Official title: 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).
Read more
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).
Read the detailed description
Italian, multicenter, phase II, biomarker trial. A total of 110 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.
- Conditions
- BRCA Mutation, PALB2 Gene Mutation, Ductal Carcinoma in Situ, Lobular Carcinoma in Situ, ATM Gene Mutation, CHEK2 Gene Mutation
- Being tested
- Tamoxifen 10 mg Tablet, Intermittent caloric restriction, Step counter Device
- Keywords
- Low Dose Tamoxifen, Intermittent Caloric Restriction, Sex Hormone Binding Globulin, Lifestyle
- Medical subject headings
- Carcinoma, Intraductal, Noninfiltrating, Breast Carcinoma In Situ
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tamoxifen 10 mg TabletDrug
Also called Low dose tamoxifen
One tablet of Tamoxifen 10 mg every other day for 6 months
Intermittent caloric restrictionOther
"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)
Step counter DeviceBehavioural
Participants will receive personal advice on healthy lifestyle and a step counter
| Study group | Role | What they receive |
|---|---|---|
| Low dose tamoxifen | Active comparator | Tamoxifen 10 mg (1 tablet) every other day for 6 months. Receives: Drug: Tamoxifen 10 mg Tablet |
| Low dose tamoxifen + Intermittent Caloric Restriction | Active comparator | 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) Receives: Drug: Tamoxifen 10 mg Tablet; Other: Intermittent caloric restriction |
| Lifestyle intervention | Placebo comparator | Step counter device Receives: Behavioral: Step counter Device |
| Lifestyle Intervention + Intermittent Caloric Restriction | Active comparator | Step counter device + 5:2 diet (5 days/week at regular energy intake+2 days a week at an average 75% energy deficit) Receives: Other: Intermittent caloric restriction; Behavioral: Step counter Device |
What is being measured
The primary outcome is the main question the study is designed to answer.
Post intervention levels of circulating binding globulin
Sex hormone binding globulin level after 6 months of intervention
Measured: Through study completion, an average of 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2023
- Study start21 Jun 2024
- Primary completion31 Dec 2025
- Study completion31 Jul 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for BRCA MutationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- European Institute of Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- Ente Ospedaliero Ospedali Galliera, Istituto Oncologico Veneto IRCCS, Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale
- Responsible party
- Sponsor
- Investigators
- Bernardo Bonanni, MD, Principal investigator, Istituto Europeo di Oncologia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06033092
- Sponsor's protocol ID
- UID 3751
- Other IDs
- 2023-503994-39-00, 2023
- Acronym
- TOLERANT
- Status last verified
- Sep 2026
- First submitted
- 23 Aug 2023
- Last updated
- 11 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 39226292