Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Trial of Low Dose Tamoxifen in Women With Breast Intraepithelial Neoplasia - Long Term Follow-up (TAM-01)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01357772
Recruitment Status : Active, not recruiting
First Posted : May 23, 2011
Last Update Posted : April 4, 2022
Sponsor:
Collaborators:
Associazione Italiana per la Ricerca sul Cancro
European Institute of Oncology
Information provided by (Responsible Party):
Andrea DeCensi, Ente Ospedaliero Ospedali Galliera

Brief 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.


Condition or disease Intervention/treatment Phase
Carcinoma, Intraductal, Noninfiltrating Recurrence, Local Neoplasm Breast Neoplasms Atypical Hyperplasia Drug: Tamoxifen Drug: placebo Phase 3

Detailed 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Tamoxifen
tamoxifen at daily dose of 5 mg for a total treatment time of 3 years
Drug: Tamoxifen
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
Drug: placebo



Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.

  2. 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).

  3. CYP2D6 polymorphisms analysis [ Time Frame: 20 years ]
    Esploratory analisis of some SNPS of the cytochrome P450 genes involved in tamoxifen metabolism such as CYP2D6



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

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


Locations
Layout table for location information
Italy
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
Sponsors and Collaborators
Andrea DeCensi
Associazione Italiana per la Ricerca sul Cancro
European Institute of Oncology
Investigators
Layout table for investigator information
Principal Investigator: Andrea De Censi, MD E.O.Ospedali Galliera
Additional Information:
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Andrea DeCensi, Medical Oncology Director, Ente Ospedaliero Ospedali Galliera
ClinicalTrials.gov Identifier: NCT01357772    
Other Study ID Numbers: GAL 01
First Posted: May 23, 2011    Key Record Dates
Last Update Posted: April 4, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Authors are open to share data based on a request for collaboration that includes a data analysis plan.

Please send an e-mail to both: andrea.decensi@galliera.it; mpuntoni@ao.pr.it

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Keywords provided by Andrea DeCensi, Ente Ospedaliero Ospedali Galliera:
DCIS
tamoxifen
dose reduction
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Breast Neoplasms
Carcinoma, Intraductal, Noninfiltrating
Neoplasm Recurrence, Local
Recurrence
Hyperplasia
Disease Attributes
Pathologic Processes
Neoplasms by Site
Breast Diseases
Skin Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Breast Carcinoma In Situ
Carcinoma in Situ
Neoplasms, Ductal, Lobular, and Medullary
Neoplastic Processes
Tamoxifen
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents