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

Breast Cancer Clinical Trial

— LIBER  

Official title:

Prevention of Breast Cancer by Letrozole in Post-menopausal Women Carrying a BRCA1/BRCA2 Mutation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00673335
• Other study ID #: UC-0104/0701 - ONCO03
• Secondary ID: ONCO-03/0701EU-2
• Status: Completed
• Phase: Phase 3
• Start date: May 2008
• Est. completion date: December 2023

Study information

• Verified date: February 2024
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 170
• Est. completion date: December 2023
• Est. primary completion date: June 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 40 Years to 69 Years

Eligibility

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

Related Conditions & MeSH terms

• brca1 Mutation Carrier
• brca2 Mutation Carrier
• Breast Cancer
• Breast Neoplasms
• Hereditary Breast/Ovarian Cancer (brca1, brca2)
• Ovarian Neoplasms

Intervention

Drug:
• letrozole

• Placebo

Locations

Country	Name	City	State
France	Institut Sainte Catherine	Avignon
France	Centre Regional Francois Baclesse	Caen
France	Centre Jean Perrin	Clermont-Ferrand
France	Centre Oscar Lambret	Lille
France	Centre Leon Berard	Lyon
France	Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes	Marseille
France	Hopital Arnaud de Villeneuve	Montpellier
France	Centre Catherine de Sienne	Nantes
France	Centre Antoine Lacassagne	Nice
France	Centre Hospitalier General de Niort	Niort
France	Hopital Saint Michel	Paris
France	Hotel Dieu de Paris	Paris
France	Institut Curie Hopital	Paris
France	CHU Poitiers	Poitiers
France	Polyclinique De Courlancy	Reims
France	Centre Eugene Marquis	Rennes
France	Centre Henri Becquerel	Rouen
France	Centre Rene Huguenin	Saint Cloud
France	CHU Sainte-Etienne - Hopital Nord	Saint-Étienne
France	Centre Paul Strauss	Strasbourg
France	Institut Claudius Regaud	Toulouse
France	Centre Alexis Vautrin	Vandoeuvre-les-Nancy
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
UNICANCER

Country where clinical trial is conducted

France, 

References & Publications (2)

Pujol P, Lasset C, Berthet P, Dugast C, Delaloge S, Fricker JP, Tennevet I, Chabbert-Buffet N, This P, Baudry K, Lemonnier J, Roca L, Mijonnet S, Gesta P, Chiesa J, Dreyfus H, Vennin P, Delnatte C, Bignon YJ, Lortholary A, Prieur F, Gladieff L, Lesur A, Clough KB, Nogues C, Martin AL; French Federation of Cancer Centres (FNCLCC). Uptake of a randomized breast cancer prevention trial comparing letrozole to placebo in BRCA1/2 mutations carriers: the LIBER trial. Fam Cancer. 2012 Mar;11(1):77-84. doi: 10.1007/s10689-011-9484-4. — View Citation

Pujol P, Mijonnet S, Karen S, et al.: Breast cancer prevention by letrozole in post menopausal BRCA1/2 mutations carriers: The Onco-03/LIBER trial. [Abstract] 32nd Annual San Antonio Breast Cancer Symposium, December 9-13, 2009, San Antonio, Texas. A-1048

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival without contralateral or unilateral invasive breast cancer at 5 years (prior breast cancer)		2017
Primary	Survival without invasive breast cancer at 5 years		2017
Secondary	Invasive cancer-free survival at 10 years		2022
Secondary	Breast cancer in situ-free survival at 5 and 10 years		2022
Secondary	Relapse-free (local or metastatic disease) survival in patients with history of breast cancer at 5 and 10 years		2017 and 2022
Secondary	Second cancer-free survival at 5 and 10 years		2017 and 2022
Secondary	Event- free (local relapse or metastatic, contralateral, or second cancer) survival at 5 and 10 years		2017 and 2022
Secondary	Overall survival at 5 and 10 years		2017 and 2022
Secondary	Toxicity according to CTCAE version 3.0		2017 and 2022
Secondary	Lipid tolerance or cardiovascular or bone event		2017 and 2022
Secondary	Quality of life according to MRS and SF36 questionnaires		2017 and 2022