Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation (LIBER)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
UNICANCER
ClinicalTrials.gov Identifier:
NCT00673335
First received: May 6, 2008
Last updated: August 5, 2014
Last verified: August 2014

May 6, 2008
August 5, 2014
May 2008
February 2017   (final data collection date for primary outcome measure)
  • Survival without contralateral or unilateral invasive breast cancer at 5 years (prior breast cancer) [ Time Frame: 2017 ] [ Designated as safety issue: No ]
  • Survival without invasive breast cancer at 5 years [ Time Frame: 2017 ] [ Designated as safety issue: No ]
  • Survival without contralateral or unilateral invasive breast cancer at 5 years (prior breast cancer) [ Designated as safety issue: No ]
  • Survival without invasive breast cancer at 5 years (no prior history of breast cancer) [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00673335 on ClinicalTrials.gov Archive Site
  • Invasive cancer-free survival at 10 years [ Time Frame: 2022 ] [ Designated as safety issue: No ]
  • Breast cancer in situ-free survival at 5 and 10 years [ Time Frame: 2022 ] [ Designated as safety issue: No ]
  • Relapse-free (local or metastatic disease) survival in patients with history of breast cancer at 5 and 10 years [ Time Frame: 2017 and 2022 ] [ Designated as safety issue: No ]
  • Second cancer-free survival at 5 and 10 years [ Time Frame: 2017 and 2022 ] [ Designated as safety issue: No ]
  • Event- free (local relapse or metastatic, contralateral, or second cancer) survival at 5 and 10 years [ Time Frame: 2017 and 2022 ] [ Designated as safety issue: No ]
  • Overall survival at 5 and 10 years [ Time Frame: 2017 and 2022 ] [ Designated as safety issue: No ]
  • Toxicity according to CTCAE version 3.0 [ Time Frame: 2017 and 2022 ] [ Designated as safety issue: Yes ]
  • Lipid tolerance or cardiovascular or bone event [ Time Frame: 2017 and 2022 ] [ Designated as safety issue: Yes ]
  • Quality of life according to MRS and SF36 questionnaires [ Time Frame: 2017 and 2022 ] [ Designated as safety issue: No ]
  • Invasive cancer-free survival at 10 years [ Designated as safety issue: No ]
  • Breast cancer in situ-free survival at 5 and 10 years [ Designated as safety issue: No ]
  • Relapse-free (local or metastatic disease) survival in patients with history of breast cancer at 5 and 10 years [ Designated as safety issue: No ]
  • Second cancer-free survival at 5 and 10 years [ Designated as safety issue: No ]
  • Event- free (local relapse or metastatic, contralateral, or second cancer) survival at 5 and 10 years [ Designated as safety issue: No ]
  • Overall survival at 5 and 10 years [ Designated as safety issue: No ]
  • Toxicity according to CTC-AE version 3.0 [ Designated as safety issue: Yes ]
  • Lipid tolerance or cardiovascular or bone event [ Designated as safety issue: Yes ]
  • Quality of life according to MRS and SF36 [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
Prevention of Breast Cancer by Letrozole in Post-menopausal Women Carrying a BRCA1/BRCA2 Mutation

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
  • brca1 Mutation Carrier
  • brca2 Mutation Carrier
  • Breast Cancer
  • Hereditary Breast/Ovarian Cancer (brca1, brca2)
Drug: letrozole
Other Name: Femara
  • Experimental: Treatment arm
    Letrozole, 1 tablet
    Intervention: Drug: letrozole
  • Placebo Comparator: Placebo
    Comparator, 1 tablet

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
386
February 2022
February 2017   (final data collection date for primary outcome measure)

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
Female
40 Years to 69 Years
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00673335
UC-0104/0701 - ONCO03, ONCO-03/0701, EU-20806, NOVARTIS-FNCLCC-ONCO 03/0701, 2007-000687-24
No
UNICANCER
UNICANCER
Not Provided
Study Chair: Pascal Pujol, MD Hopital Arnaud de Villeneuve
UNICANCER
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP