Trial of Low Dose Tamoxifen in Women With Breast Intraepithelial Neoplasia - Long Term Follow-up

NCT ID: NCT01357772

Last Updated: 2023-07-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

500 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-11-12

Study Completion Date

2028-12-31

Brief Summary

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The aim of the study is to evaluate whether tamoxifen at a low dose of 5mg/d reduces in the long term the incidence of invasive breast cancer and ductal carcinoma in situ, DCIS (DIN 1c, 2, 3) of the breast, in woman operated for lobular intraepithelial neoplasia (LIN1, 2 and 3) or ER-positive ductal intraepithelial neoplasia (DIN 1b, DIN2, DIN3, 1a excluded) of the breast.

To improve the risk-benefit ratio, the use of lower doses of the drug has been proposed.

Biomarker trials revealed that 5 mg/d was noninferior to 20 mg/d in inhibiting proliferation of breast cancer and normal endometrial tissue.

By contrast, the risk of endometrial cancer si dose-dependent, and the dose reduction can lead a substantial decrease. Morover a dose of 5 mg/day is associated with an overall decrease of the estrogenic activity of tamoxifen on insulin like growth factor (IGF-I), sex hormone-binding globulin (SHBG) and antithrombin-III, with a decrease of venous thromboembolic events. Moreover, tamoxifen exhibits a high tissue distribution, so that a dose of 5 mg/day attains at the breast tissue level a concentration 10 times higher than that needed to inhibit cell growth in vitro.

A prospective cohort study also showed that 10 mg on alternate days halves recurrence of DCIS in postmenopausal women.

It has been shown that the treatment of dysplasia or pre-cancer drives the reduction of the invasive neoplasms onset. This is a chemoprevention trial designed to validatate the low-dose Tamoxifen in women with diseases at high evolutionary risk. The demonstration of efficacy and safety of such a treatment for the prevention of the invasive breast cancer would lead improvements in term of survival and quality of life for the patients at increased risk.

Detailed Description

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Italian, multicenter, phase III trial: controlled, parallel group comparision, randomized (1:1) duble blind, tamoxifen 5 mg/d versus placebo administered for 3 years. A total of 500 women 75 years of age or younger with newly diagnosed non-invasive breast cancer have been included in the study. The long-term study implies a minimum 10 year follow up after treatment completion.

Conditions

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Carcinoma, Intraductal, Noninfiltrating Recurrence, Local Neoplasm Breast Neoplasms Atypical Hyperplasia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Tamoxifen

tamoxifen at daily dose of 5 mg for a total treatment time of 3 years

Group Type EXPERIMENTAL

Tamoxifen

Intervention Type DRUG

placebo

placebo at daily dose of 5 mg for a total treatment time of 3 years

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Interventions

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Tamoxifen

Intervention Type DRUG

placebo

Intervention Type DRUG

Other Intervention Names

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Tamoxifen citrate (ATC code: L02BA01)

Eligibility Criteria

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Inclusion Criteria

1. Women of age ≥ 18 and \< 75 years
2. Women operated on for lobular (LIN 2 and 3) or ER positive or unknown ductal DCIS, i.e DIN 1-3, but DIN 1a excluded) intraepithelial neoplasia in the 5 years (60 months) prior the inclusion in the study. Both incident (diagnosis \< 12 months) and prevalent cases diagnosis ≥12, and \< 60 months) will be included, including recurrent cases
3. ECOG Performance status ≤ 1
4. Written informed consent

Exclusion Criteria

1. Any type of malignancy, with the exclusion of non-melanoma skin cancer
2. Proliferative disorders of the endometrium such as atypical hyperplasia, endometriosis, unresected polyps, symptomatic myoma
3. Liver, kidney and heart function impairment grade ≥ 2 (CTCAE criteria v.3.0)
4. Any type of retinal disorders, severe cataract and glaucoma
5. Presence of significant risk factors for venous events, including immobilization after trauma within the last 3 months for longer than 2 weeks, deep venous thrombophlebitis or other significant venous thrombotic event,VTE (pulmonary embolism, stroke, etc.)
6. Use of tamoxifen, raloxifene or other selective estrogen receptor modulator (SERMs)
7. Use of anastrozole and other aromatase inhibitors (AI) in the last 12 months for ≥ 6 months
8. Dicoumarol anticoagulant therapy in progress
9. Active infections
10. Severe psychiatric disorders or inability to comply to the protocol procedures
11. Geographic inaccessibility or difficulties in ensuring adequate compliance
12. Women who are pregnant or breastfeeding
13. Any other factor which, at the discretion of the investigator, may controindicate the use of tamoxifen
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Associazione Italiana per la Ricerca sul Cancro

OTHER

Sponsor Role collaborator

European Institute of Oncology

OTHER

Sponsor Role collaborator

Andrea DeCensi

OTHER

Sponsor Role lead

Responsible Party

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Andrea DeCensi

Medical Oncology Director

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Andrea DeCensi, MD

Role: PRINCIPAL_INVESTIGATOR

E.O.Ospedali Galliera

Locations

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Ospedali riuniti ASL AL - Ospedale SS. Antonio e Margherita

Tortona, Alessandria, Italy

Site Status

Istituto Scientifico Romagnolo per lo studio e la cura dei tumori

Meldola, Forlì-Cesena, Italy

Site Status

Ospedale di Carpi "Bernardino Ramazzini"

Carpi, Modena, Italy

Site Status

IRCCS Istituto Tumori Giovanni Paolo II

Bari, , Italy

Site Status

Azienda Ospedaliera Mater Domini Catanzaro

Catanzaro, , Italy

Site Status

E.O. Ospedali Galliera

Genoa, , Italy

Site Status

IEO - European Institute of Oncology IRCCS

Milan, , Italy

Site Status

Azienda Ospedaliera-Universitaria Policlinico di Modena

Modena, , Italy

Site Status

Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

Napoli, , Italy

Site Status

ICS Maugeri -Centro Medico di Pavia

Pavia, , Italy

Site Status

AUSL - Oncologia Medica

Ravenna, , Italy

Site Status

Azienda Ospedaliera-Universitaria Città della Salute e della Scienza di Torino

Torino, , Italy

Site Status

Azienda Socio-Sanitaria Territoriale Sette Laghi, Varese

Varese, , Italy

Site Status

Azienda ULSS8 Berica

Vicenza, , Italy

Site Status

Countries

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Italy

References

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DeCensi A, Puntoni M, Johansson H, Guerrieri-Gonzaga A, Caviglia S, Avino F, Cortesi L, Ponti A, Pacquola MG, Falcini F, Gulisano M, Digennaro M, Cariello A, Cagossi K, Pinotti G, Lazzeroni M, Serrano D, Briata IM, Buttiron Webber T, Boni L, Bonanni B. Effect Modifiers of Low-Dose Tamoxifen in a Randomized Trial in Breast Noninvasive Disease. Clin Cancer Res. 2021 Jul 1;27(13):3576-3583. doi: 10.1158/1078-0432.CCR-20-4213. Epub 2021 Feb 19.

Reference Type RESULT
PMID: 33608319 (View on PubMed)

Lazzeroni M, Serrano D, Dunn BK, Heckman-Stoddard BM, Lee O, Khan S, Decensi A. Oral low dose and topical tamoxifen for breast cancer prevention: modern approaches for an old drug. Breast Cancer Res. 2012 Oct 29;14(5):214. doi: 10.1186/bcr3233.

Reference Type RESULT
PMID: 23106852 (View on PubMed)

DeCensi A, Johansson H, Helland T, Puntoni M, Macis D, Aristarco V, Caviglia S, Webber TB, Briata IM, D'Amico M, Serrano D, Guerrieri-Gonzaga A, Bifulco E, Hustad S, Soiland H, Boni L, Bonanni B, Mellgren G. Association of CYP2D6 genotype and tamoxifen metabolites with breast cancer recurrence in a low-dose trial. NPJ Breast Cancer. 2021 Mar 25;7(1):34. doi: 10.1038/s41523-021-00236-6.

Reference Type RESULT
PMID: 33767162 (View on PubMed)

Lazzeroni M, Puntoni M, Guerrieri-Gonzaga A, Serrano D, Boni L, Buttiron Webber T, Fava M, Briata IM, Giordano L, Digennaro M, Cortesi L, Falcini F, Serra P, Avino F, Millo F, Cagossi K, Gallerani E, De Simone A, Cariello A, Aprile G, Renne M, Bonanni B, DeCensi A. Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Recurrence in Breast Noninvasive Neoplasia: A 10-Year Follow-Up of TAM-01 Study. J Clin Oncol. 2023 Jun 10;41(17):3116-3121. doi: 10.1200/JCO.22.02900. Epub 2023 Mar 14.

Reference Type RESULT
PMID: 36917758 (View on PubMed)

Carbone A, Oliva M, Puntoni M, Guerrieri-Gonzaga A, Briata IM, Lazzeroni M, Serrano D, Giordano L, Digennaro M, Cortesi L, Millo F, Cagossi K, Aprile G, Serra P, Gallerani E, Bonanni B, DeCensi A. Effect of low-dose tamoxifen on benign gynecological and breast conditions in a phase III trial in non-invasive breast cancer. J Natl Cancer Inst. 2025 Aug 28:djaf250. doi: 10.1093/jnci/djaf250. Online ahead of print.

Reference Type DERIVED
PMID: 40880294 (View on PubMed)

DeCensi A, Puntoni M, Guerrieri-Gonzaga A, Caviglia S, Avino F, Cortesi L, Taverniti C, Pacquola MG, Falcini F, Gulisano M, Digennaro M, Cariello A, Cagossi K, Pinotti G, Lazzeroni M, Serrano D, Branchi D, Campora S, Petrera M, Buttiron Webber T, Boni L, Bonanni B. Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Local and Contralateral Recurrence in Breast Intraepithelial Neoplasia. J Clin Oncol. 2019 Jul 1;37(19):1629-1637. doi: 10.1200/JCO.18.01779. Epub 2019 Apr 11.

Reference Type DERIVED
PMID: 30973790 (View on PubMed)

Related Links

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Other Identifiers

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2007-007740-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GAL 01

Identifier Type: -

Identifier Source: org_study_id

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