Breast cancer prevention in women at increased risk using low dose tamoxifen and/or diet and life style changes: a randomized 4 arms clinical study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Istituto Europeo Di Oncologia S.r.l.

Participant type

Patients, Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Jun 2024 → ongoing

Decision date (initial)

2023-07-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Ministero della Salute ( ref. PNRR-MAD-2022-12376567)

External identifiers

EU CT number

2023-503994-39-00

ClinicalTrials.gov

NCT06033092

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

The main aim is to verify whether Low Dose Tamoxifen (LDT) increases circulating Sex Hormone Binding Globulin (SHBG) more than lifestyle intervention (LI) with or without intermittent caloric restriction (ICR) after 6 months of intervention

Secondary objectives 4

1. to verify whether ICR significantly modulates main and secondary endpoints such as HOMA-index, inflammatory markers, lipid profile, Adiponectin/Leptin (A/L) ratio, quality of life (QoL), Body mass index (BMI), body composition, safety and toxicity
2. 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
3. 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
4. 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)

Conditions and MedDRA coding

Healthy women aged 18-70 either carriers of a germline pathogenetic variant (BRCA1, BRCA2, PALB2, ATM, CHEK2, CDH1, RAD51C or RAD51D) or with a breast cancer risk >5% at 10 years (according to the Tyrer-Cuzick model or the Breast Cancer Surveillance Consortium Risk models) or with a previously treated breast IEN (intraepithelial neoplasia).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Women between 18 and 70 years old
2. 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% BC 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. 3. Ability to understand and the willingness to sign a written informed consent document.
4. 4. ECOG performance status ≤1 (Karnofsky ≥70%)
5. 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
6. 5b. For IEN Strata: A bilateral mammogram within 12 months before baseline visit is required. The diagnostic mammogram (i.e. before breast surgery) is acceptable
7. 6. A negative transvaginal ultrasound/hysteroscopy within 6 months before baseline visit. Women with a previous hysterectomy due to a benign condition, are not required a transvaginal ultrasound.

Exclusion criteria 10

1. 1. Diagnosis of ER negative (<10%) DCIS, or history of breast invasive cancer
2. 2. Previous treatment with SERMs or any other hormonal treatment for breast neoplasms
3. 3. BMI < 18.5 Kg/m2 and/or Malnutrition Universal Screening Tool (MUST) score ≥2 and/or any current or past eating disorders
4. 4. Any diagnosis of invasive neoplasia, except non-melanoma skin cancer, in the previous 5 years
5. 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 or cataract)
6. 6. Current use of warfarin or other anticoagulant drugs
7. 7. Bilateral mastectomy
8. 8. Pregnancy or desire to become pregnant in the subsequent 9 months after treatment cessation
9. 9. Diabetes or any other clinical condition that at the investigator’s discretion contraindicates the proposed intervention
10. 10. No hormonal contraception is allowed during study intervention. Non-hormonal methods will be advised for women of childbearing potential (WOCBP).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Post intervention levels of circulating Sex Hormone Binding Globulin (SHBG)

Secondary endpoints 6

1. Changes in time of serum biomarkers: SHBG, insulin, glucose, lipid profile, IGF-I, IGFBP-1, -2 and -3, hs-CRP, adiponectin and leptin;
2. Changes in time of safety and toxicity
3. Changes in time of quality of life
4. Changes in time of BMI and body composition
5. Changes in time of microbiome composition
6. Changes in time of immune modulation by expression of inflammation cell signaling genes

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Istituto Europeo Di Oncologia S.r.l.

Sponsor organisation

Istituto Europeo Di Oncologia S.r.l.

Address

Via Giuseppe Ripamonti 435

City

Milan

Postcode

20141

Country

Italy

Scientific contact point

Organisation

Istituto Europeo Di Oncologia S.r.l.

Contact name

Bernardo Bonanni

Public contact point

Organisation

Istituto Europeo Di Oncologia S.r.l.

Contact name

Bernardo Bonanni

Third parties 1

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications