Trial of Low Dose Tamoxifen in Women With Breast Intraepithelial Neoplasia - Long Term Follow-up (TAM-01)
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|ClinicalTrials.gov Identifier: NCT01357772|
Recruitment Status : Active, not recruiting
First Posted : May 23, 2011
Last Update Posted : April 4, 2022
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.
|Condition or disease||Intervention/treatment||Phase|
|Carcinoma, Intraductal, Noninfiltrating Recurrence, Local Neoplasm Breast Neoplasms Atypical Hyperplasia||Drug: Tamoxifen Drug: placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||500 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||Randomized Placebo-controlled Phase III Trial of Low Dose Tamoxifen in Women With Breast Intraepithelial Neoplasia - Long Term Follow-up|
|Study Start Date :||November 12, 2008|
|Estimated Primary Completion Date :||December 31, 2028|
|Estimated Study Completion Date :||December 31, 2028|
tamoxifen at daily dose of 5 mg for a total treatment time of 3 years
Other Name: Tamoxifen citrate (ATC code: L02BA01)
Placebo Comparator: placebo
placebo at daily dose of 5 mg for a total treatment time of 3 years
- Number of invasive breast cancer events and DCIS [ Time Frame: 20 years ]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
- Number of other non-invasive breast events [ Time Frame: 20 years ]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.
- Metabolites of tamoxifen and hormone blood level (in a subgroup of women) [ Time Frame: 20 years ]Blood concentrations of metabolites including circulating IGF-I,IGFBP-3, SHBG, hormones (testosterone, estradiol, SHBG, CRP), tamoxifen metabolites (4OH tamoxifen and endoxifen).
- CYP2D6 polymorphisms analysis [ Time Frame: 20 years ]Esploratory analisis of some SNPS of the cytochrome P450 genes involved in tamoxifen metabolism such as CYP2D6
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01357772
|Istituto Scientifico Romagnolo per lo studio e la cura dei tumori|
|Meldola, Forlì-Cesena, Italy, 47521|
|Ospedale di Carpi "Bernardino Ramazzini"|
|Carpi, Modena, Italy, 41012|
|IRCCS Ospedale Oncologico di Bari - Istituto tumori "G. Paolo II"|
|Bari, Italy, 70124|
|E.O. Ospedali Galliera|
|Genoa, Italy, 16128|
|Istituto Europeo di Oncologia|
|Milano, Italy, 20100|
|A. O. Universitaria Policlinico di Modena|
|Modena, Italy, 41100|
|Istituto nazionale per lo studio e la cura dei tumori, IRCCS "Fondazione Pascale"|
|Napoli, Italy, 80131|
|AUSL - Oncologia Medica|
|Ravenna, Italy, 48018|
|A.O. Universitaria S. Giovanni Battista - "Le Molinette"|
|Torino, Italy, 10123|
|Presidio Ospedaliero "SS. Antonio e Margherita"|
|Tortona, Italy, 15057|
|Azienda ULSS8 Berica|
|Vicenza, Italy, 36100|
|Principal Investigator:||Andrea De Censi, MD||E.O.Ospedali Galliera|