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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by UNICANCER
Sponsor:
Information provided by (Responsible Party):
UNICANCER
ClinicalTrials.gov Identifier:
NCT00673335
First received: May 6, 2008
Last updated: June 17, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
brca1 Mutation Carrier
brca2 Mutation Carrier
Breast Cancer
Hereditary Breast/Ovarian Cancer (brca1, brca2)
Drug: letrozole
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Prevention of Breast Cancer by Letrozole in Post-menopausal Women Carrying a BRCA1/BRCA2 Mutation

Resource links provided by NLM:


Further study details as provided by UNICANCER:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 386
Study Start Date: May 2008
Estimated Study Completion Date: February 2022
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment arm
Letrozol, 1 tablet
Drug: letrozole
Other Name: Femara
Placebo Comparator: Placebo
Comparator, 1 tablet

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.

  Eligibility

Ages Eligible for Study:   40 Years to 69 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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 (including curatorship)

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00673335

Locations
France
Institut Sainte Catherine Recruiting
Avignon, France, 84082
Contact: Contact Person    33-490-27-61-61      
Centre Regional Francois Baclesse Recruiting
Caen, France, 14076
Contact: Contact Person    33-2-3145-5000      
Centre Jean Perrin Recruiting
Clermont-Ferrand, France, 63011
Contact: Contact Person    33-73-278-080      
Centre Oscar Lambret Recruiting
Lille, France, 59020
Contact: Contact Person    33-32-029-5959      
Centre Leon Berard Recruiting
Lyon, France, 69373
Contact: Contact Person    33-4-78-78-26-45      
Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes Recruiting
Marseille, France, 13273
Contact: Contact Person    33-4-9122-3700      
Hopital Arnaud de Villeneuve Recruiting
Montpellier, France, 34295
Contact: Contact Person    33-467-335-875      
Centre Catherine de Sienne Recruiting
Nantes, France, 02
Contact: Contact Person    33-40-02-28-272-000      
Centre Antoine Lacassagne Recruiting
Nice, France, 06189
Contact: Contact Person    33-49-203-1000      
Centre Hospitalier General de Niort Recruiting
Niort, France, 79021
Contact: Contact Person    33-5-4932-7979      
Hopital Saint Michel Recruiting
Paris, France, 75015
Contact: Contact Person    33-1-4045-6363      
Hotel Dieu de Paris Recruiting
Paris, France, 75181
Contact: Contact Person    33-1-42-348-413      
Institut Curie Hopital Recruiting
Paris, France, 75248
Contact: Contact Person    33-44-32-4000      
CHU Poitiers Recruiting
Poitiers, France, 86021
Contact: Contact Person    33-549-444-538      
Polyclinique De Courlancy Recruiting
Reims, France, F-51100
Contact: Contact Person    33-3-2677-2777      
Centre Eugene Marquis Recruiting
Rennes, France, 35042
Contact: Contact Person    33-2-9925-3000      
Centre Henri Becquerel Recruiting
Rouen, France, 76038
Contact: Contact Person    33-2-3208-2222      
Centre Rene Huguenin Recruiting
Saint Cloud, France, 92211
Contact: Contact Person    33-1-47-111-515      
CHU Sainte-Etienne - Hopital Nord Recruiting
Sainte-Etienne, France, 42055
Contact: Contact Person    33-4-77-82-80-00      
Centre Paul Strauss Recruiting
Strasbourg, France, 67065
Contact: Contact Person    33-3-8825-2424      
Institut Claudius Regaud Recruiting
Toulouse, France, 31052
Contact: Contact Person    33-5-6142-4242      
Centre Alexis Vautrin Recruiting
Vandoeuvre-les-Nancy, France, 54511
Contact: Contact Person    33-3-8359-8400      
Institut Gustave Roussy Recruiting
Villejuif, France, F-94805
Contact: Contact Person    33-1-4211-4339      
Sponsors and Collaborators
UNICANCER
Investigators
Study Chair: Pascal Pujol, MD Hopital Arnaud de Villeneuve
  More Information

Publications:
Responsible Party: UNICANCER
ClinicalTrials.gov Identifier: NCT00673335     History of Changes
Other Study ID Numbers: UC-0104/0701 - ONCO03, ONCO-03/0701, EU-20806, NOVARTIS-FNCLCC-ONCO 03/0701, 2007-000687-24
Study First Received: May 6, 2008
Last Updated: June 17, 2013
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by UNICANCER:
breast cancer
hereditary breast/ovarian cancer (BRCA1, BRCA2)
BRCA1 mutation carrier
BRCA2 mutation carrier

Additional relevant MeSH terms:
Breast Neoplasms
Ovarian Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Letrozole
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014