Trial | NCT01357772  Report issue

Title

Trial of Low Dose Tamoxifen in Women With Breast Intraepithelial Neoplasia - Long Term Follow-up
Randomized Placebo-controlled Phase III Trial of Low Dose Tamoxifen in Women With Breast Intraepithelial Neoplasia - Long Term Follow-up

  • Phase

    Phase 3

  • Study Type

    Interventional

  • Status

    Active, not recruiting

  • Intervention/Treatment

    tamoxifen ...

  • Study Participants

    500
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.
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.
Study Started
Nov 12
2008
Primary Completion
Dec 31
2022
Study Completion
Dec 31
2028
Anticipated
Last Update
Jul 17
2023

Drug Tamoxifen

  • Other names: Tamoxifen citrate (ATC code: L02BA01)

Drug placebo

Tamoxifen Experimental

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

placebo Placebo Comparator

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

Criteria 

Inclusion Criteria:

Women of age ≥ 18 and < 75 years
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
ECOG Performance status ≤ 1
Written informed consent

Exclusion Criteria:

Any type of malignancy, with the exclusion of non-melanoma skin cancer
Proliferative disorders of the endometrium such as atypical hyperplasia, endometriosis, unresected polyps, symptomatic myoma
Liver, kidney and heart function impairment grade ≥ 2 (CTCAE criteria v.3.0)
Any type of retinal disorders, severe cataract and glaucoma
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.)
Use of tamoxifen, raloxifene or other selective estrogen receptor modulator (SERMs)
Use of anastrozole and other aromatase inhibitors (AI) in the last 12 months for ≥ 6 months
Dicoumarol anticoagulant therapy in progress
Active infections
Severe psychiatric disorders or inability to comply to the protocol procedures
Geographic inaccessibility or difficulties in ensuring adequate compliance
Women who are pregnant or breastfeeding
Any other factor which, at the discretion of the investigator, may controindicate the use of tamoxifen
No Results Posted