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

NCT00673335 | Completed Phase 3 DMC

• 5 other identifiers: UC-0104/0701 - ONCO03ONCO-03/0701EU-20806NOVARTIS-FNCLCC-ONCO 03/07012007-000687-24
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 23

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.

Conditions

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

Keywords

breast cancer; hereditary breast/ovarian cancer (BRCA1, BRCA2); BRCA1 mutation carrier; BRCA2 mutation carrier

Outcome Measures

Primary Outcomes (2)

• Survival without contralateral or unilateral invasive breast cancer at 5 years (prior breast cancer)

  2017

• Survival without invasive breast cancer at 5 years

  2017

Secondary Outcomes (9)

• Invasive cancer-free survival at 10 years

  2022

• Breast cancer in situ-free survival at 5 and 10 years

  2022

• Relapse-free (local or metastatic disease) survival in patients with history of breast cancer at 5 and 10 years

  2017 and 2022

• Second cancer-free survival at 5 and 10 years

  2017 and 2022

• Event- free (local relapse or metastatic, contralateral, or second cancer) survival at 5 and 10 years

  2017 and 2022

Study Arms (2)

Treatment arm

EXPERIMENTAL

Letrozole, 1 tablet

Drug: letrozole

Placebo

PLACEBO COMPARATOR

Comparator, 1 tablet

Drug: Placebo

Interventions

letrozole DRUG

Also known as: Femara

Treatment arm

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 40 Years - 69 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (23)

Institut Sainte Catherine

Avignon, 84082, France

Location

Centre Regional Francois Baclesse

Caen, 14076, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63011, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes

Marseille, 13273, France

Location

Hopital Arnaud de Villeneuve

Montpellier, 34295, France

Location

Centre Catherine de Sienne

Nantes, 02, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Centre Hospitalier General de Niort

Niort, 79021, France

Location

Hopital Saint Michel

Paris, 75015, France

Location

Hotel Dieu de Paris

Paris, 75181, France

Location

Institut Curie Hopital

Paris, 75248, France

Location

CHU Poitiers

Poitiers, 86021, France

Location

Polyclinique De Courlancy

Reims, F-51100, France

Location

Centre Eugene Marquis

Rennes, 35042, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Centre Rene Huguenin

Saint-Cloud, 92211, France

Location

CHU Sainte-Etienne - Hopital Nord

Saint-Etienne, 42055, France

Location

Centre Paul Strauss

Strasbourg, 67065, France

Location

Institut Claudius Regaud

Toulouse, 31052, France

Location

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, 54511, France

Location

Institut Gustave Roussy

Villejuif, F-94805, France

Location

Related 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.

  PMID: 22076253 BACKGROUND

• 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.

  RESULT

MeSH Terms

Conditions

Breast Neoplasms; Hereditary Breast and Ovarian Cancer Syndrome

Interventions

Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplastic Syndromes, Hereditary; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Pascal Pujol, MD

  Hopital Arnaud de Villeneuve

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2008
• First Posted: May 7, 2008
• Study Start: May 1, 2008
• Primary Completion: June 1, 2019
• Study Completion: December 1, 2023
• Last Updated: July 1, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.
• Access Criteria: The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.

Locations

FR (23)