Overview

This trial is active, not recruiting.

Conditions brca1 mutation carrier, brca2 mutation carrier, breast cancer, hereditary breast/ovarian cancer (brca1, brca2)
Treatments letrozole, placebo
Phase phase 3
Sponsor UNICANCER
Start date May 2008
End date February 2017
Trial size 386 participants
Trial identifier NCT00673335, 2007-000687-24, EU-20806, NOVARTIS-FNCLCC-ONCO 03/0701, ONCO-03/0701, UC-0104/0701 - ONCO03

Summary

RATIONALE: Letrozole may prevent breast cancer in postmenopausal women with a BRCA1 or BRCA2 mutation.

PURPOSE: This randomized phase III trial is studying letrozole to see how well it works compared with a placebo in preventing breast cancer in postmenopausal women with a BRCA1 or BRCA2 mutation.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose prevention
Arm
(Experimental)
Letrozole, 1 tablet
letrozole Femara
(Placebo Comparator)
Comparator, 1 tablet
placebo

Primary Outcomes

Measure
Survival without contralateral or unilateral invasive breast cancer at 5 years (prior breast cancer)
time frame: 2017
Survival without invasive breast cancer at 5 years
time frame: 2017

Secondary Outcomes

Measure
Invasive cancer-free survival at 10 years
time frame: 2022
Breast cancer in situ-free survival at 5 and 10 years
time frame: 2022
Relapse-free (local or metastatic disease) survival in patients with history of breast cancer at 5 and 10 years
time frame: 2017 and 2022
Second cancer-free survival at 5 and 10 years
time frame: 2017 and 2022
Event- free (local relapse or metastatic, contralateral, or second cancer) survival at 5 and 10 years
time frame: 2017 and 2022
Overall survival at 5 and 10 years
time frame: 2017 and 2022
Toxicity according to CTCAE version 3.0
time frame: 2017 and 2022
Lipid tolerance or cardiovascular or bone event
time frame: 2017 and 2022
Quality of life according to MRS and SF36 questionnaires
time frame: 2017 and 2022

Eligibility Criteria

Female participants from 40 years up to 69 years old.

DISEASE CHARACTERISTICS: - Must meet the following criteria: - With or without invasive unilateral breast cancer more than 5 years ago, with no recurrence - No evidence of breast cancer by mammography or MRI within the past year - Carrier of the BRCA1/BRCA2 deleterious mutation (nonsense mutation or stop) - Refused preventive mastectomy - No prior bilateral breast cancer - No prior bilateral mastectomy - Hormone receptor status not specified PATIENT CHARACTERISTICS: Inclusion criteria: - Menopausal status as indicated by 1 of the following criteria: - Age > 60 years - Bilateral oophorectomy - Age ≤ 60 years with no hysterectomy or amenorrhea within the past 12 months - Age ≤ 60 years with prior hysterectomy or FSH > 20 IU/L - Eastern Cooperative Oncology Group (ECOG) or WHO performance status 0-1 - absolute neutrophil count (ANC) > 2,000/mm^3 - Platelet count > 100,000/mm^3 - Hemoglobin > 10 g/dL - Bilirubin normal - ALT and AST < 2.5 times upper limit of normal - Creatinine clearance ≥ 60 mL/min - Adequate cardiovascular function (e.g., no history of myocardial infarction, angina pectoris, or heart failure) - No osteoporosis by bone density scan (DEXA) within the past 2 years or prior osteoporotic fracture (femur, lumbar spine T score > -2 DS) Exclusion criteria: - Invasive cancer diagnosed in the past 5 years, except for basal cell or squamous cell skin cancer or carcinoma in situ of the cervix - Prior cerebrovascular accident - Prior cardiac ischemia - Hypersensitivity to letrozole or its excipients, especially titanium oxide - Renal or hepatocellular insufficiency, cholestasis, or cytolysis - Geographical, social, or psychological reasons that preclude medical monitoring in this study - Deprived of liberty or guardianship PRIOR CONCURRENT THERAPY: - See Disease Characteristics - At least 3 months since prior and no concurrent hormone replacement therapy (e.g., thyroid-stimulating hormone) - No prior hormonal therapy in the past year - No concurrent participation in another therapeutic study with an experimental drug

Additional Information

Official title Prevention of Breast Cancer by Letrozole in Post-menopausal Women Carrying a BRCA1/BRCA2 Mutation
Description OBJECTIVES: Primary - Evaluate the reduction of the incidence of invasive breast cancer in postmenopausal women with the BRCA1/BRCA2 mutation treated with letrozole. Secondary - Determine the reduction of the incidence of in situ breast cancer in these women. - Determine the recurrence rate of local or metastatic disease in women who have had breast cancer. - Determine the incidence of non-breast cancer, especially ovarian, colon, or endometrial cancer. - Assess the tolerance of this drug in terms of lipid, cardiovascular, and bone effects. - Determine the quality of life of women treated with this drug. - Identify serological markers that allow early diagnosis of hereditary predisposition for breast cancer. - Conduct pharmacogenetic analysis. - Identify biomarkers or genes involved in the occurrence of cardiovascular and rheumatologic metabolic aromatase inhibitors. - Study the phenotypic characteristics of cancers that occur during treatment with letrozole, in particular hormonal markers (estrogen and progesterone receptor) and expression profiles of resistance to therapy. OUTLINE: This is a multicenter study. Patients are stratified according to nature of mutation (BRCA1 vs BRCA2), oophorectomy in premenopausal state (yes vs no), and prior breast cancer (yes vs no). Patients are randomized to 1 of 2 treatment arms. - Arm I: Patients receive oral letrozole once daily. - Arm II: Patients receive oral placebo once daily. Treatment in both arms continues for 5 years in the absence of unacceptable toxicity or development of cancer or recurrent disease. Blood samples are collected periodically for pharmacogenetic studies and analysis of biomarkers or genes associated with hereditary predisposition for breast cancer, toxicities, and resistance to therapy. After completion of study treatment, patients are followed for 5 years.
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by UNICANCER.