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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT01357772
Other study ID # GAL 01
Secondary ID 2007-007740-10
Status Active, not recruiting
Phase Phase 3
First received
Last updated
Start date November 12, 2008
Est. completion date December 31, 2028

Study information

Verified date July 2023
Source Ente Ospedaliero Ospedali Galliera
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Description:

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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 500
Est. completion date December 31, 2028
Est. primary completion date December 31, 2022
Accepts healthy volunteers No
Gender Female
Age group 18 Years to 75 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Tamoxifen

placebo


Locations

Country Name City State
Italy IRCCS Istituto Tumori Giovanni Paolo II Bari
Italy Ospedale di Carpi "Bernardino Ramazzini" Carpi Modena
Italy Azienda Ospedaliera Mater Domini Catanzaro Catanzaro
Italy E.O. Ospedali Galliera Genoa
Italy Istituto Scientifico Romagnolo per lo studio e la cura dei tumori Meldola Forlì-Cesena
Italy IEO - European Institute of Oncology IRCCS Milan
Italy Azienda Ospedaliera-Universitaria Policlinico di Modena Modena
Italy Istituto Nazionale Tumori IRCCS Fondazione G. Pascale Napoli
Italy ICS Maugeri -Centro Medico di Pavia Pavia
Italy AUSL - Oncologia Medica Ravenna
Italy Azienda Ospedaliera-Universitaria Città della Salute e della Scienza di Torino Torino
Italy Ospedali riuniti ASL AL - Ospedale SS. Antonio e Margherita Tortona Alessandria
Italy Azienda Socio-Sanitaria Territoriale Sette Laghi, Varese Varese
Italy Azienda ULSS8 Berica Vicenza

Sponsors (3)

Lead Sponsor Collaborator
Andrea DeCensi Associazione Italiana per la Ricerca sul Cancro, European Institute of Oncology

Country where clinical trial is conducted

Italy, 

References & Publications (4)

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 me — View Citation

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. Ef — View Citation

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, — View Citation

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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Number of invasive breast cancer events and DCIS Number of neoplastic events, i.e., invasive breast cancer or ductal carcinoma in situ of the breast from the start of treatment up to at least 16 years from treatment initiation. 20 years
Secondary Number of other non-invasive breast events Number of other non-invasive breast disorders (LCIS, atypical ductal or lobular hyperplasia), endometrial cancer, ovarian cancer, thromboembolic events; bone fractures, cardiovascular and thromboembolic events, clinically manifested cataracts and melanoma; change of mammographic density from the start of treatment up to at least 16 years from treatment initiation. 20 years
Secondary Metabolites of tamoxifen and hormone blood level (in a subgroup of women) Blood concentrations of metabolites including circulating IGF-I,IGFBP-3, SHBG, hormones (testosterone, estradiol, SHBG, CRP), tamoxifen metabolites (4OH tamoxifen and endoxifen). 20 years
Secondary CYP2D6 polymorphisms analysis Esploratory analisis of some SNPS of the cytochrome P450 genes involved in tamoxifen metabolism such as CYP2D6. 20 years
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