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

NCT ID: NCT00673335

Last Updated: 2024-07-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 170 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-05-31
• Study Completion Date: 2023-12-31

Brief 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.

Detailed 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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Treatment arm

Letrozole, 1 tablet

Group Type: EXPERIMENTAL

letrozole

Intervention Type: DRUG

Placebo

Comparator, 1 tablet

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

letrozole

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Femara

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

UNICANCER

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pascal Pujol, MD

Role: STUDY_CHAIR

Hopital Arnaud de Villeneuve

Locations

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-Etienne, , France

Centre Paul Strauss

Strasbourg, , France

Institut Claudius Regaud

Toulouse, , France

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, , France

Institut Gustave Roussy

Villejuif, , France

Countries

France

References

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.

Reference Type: BACKGROUND

PMID: 22076253 (View on PubMed)

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, 2009.

Reference Type: RESULT

Other Identifiers

ONCO-03/0701

Identifier Type: OTHER

Identifier Source: secondary_id

EU-20806

Identifier Type: -

Identifier Source: secondary_id

NOVARTIS-FNCLCC-ONCO 03/0701

Identifier Type: -

Identifier Source: secondary_id

2007-000687-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

UC-0104/0701 - ONCO03

Identifier Type: -

Identifier Source: org_study_id