Back to resultsLetrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation (LIBER)
Primary Purpose
brca1 Mutation Carrier, brca2 Mutation Carrier, Breast Cancer
Status
Active
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
letrozole
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for brca1 Mutation Carrier focused on measuring breast cancer, hereditary breast/ovarian cancer (BRCA1, BRCA2), BRCA1 mutation carrier, BRCA2 mutation carrier
Eligibility 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
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
Sites / Locations
- Institut Sainte Catherine
- Centre Regional Francois Baclesse
- Centre Jean Perrin
- Centre Oscar Lambret
- Centre Leon Berard
- Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
- Hopital Arnaud de Villeneuve
- Centre Catherine de Sienne
- Centre Antoine Lacassagne
- Centre Hospitalier General de Niort
- Hopital Saint Michel
- Hotel Dieu de Paris
- Institut Curie Hopital
- CHU Poitiers
- Polyclinique De Courlancy
- Centre Eugene Marquis
- Centre Henri Becquerel
- Centre Rene Huguenin
- CHU Sainte-Etienne - Hopital Nord
- Centre Paul Strauss
- Institut Claudius Regaud
- Centre Alexis Vautrin
- Institut Gustave Roussy
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Treatment arm
Placebo
Arm Description
Letrozole, 1 tablet
Comparator, 1 tablet
Outcomes
Primary Outcome Measures
Survival without contralateral or unilateral invasive breast cancer at 5 years (prior breast cancer)
Survival without invasive breast cancer at 5 years
Secondary Outcome Measures
Invasive cancer-free survival at 10 years
Breast cancer in situ-free survival at 5 and 10 years
Relapse-free (local or metastatic disease) survival in patients with history of breast cancer at 5 and 10 years
Second cancer-free survival at 5 and 10 years
Event- free (local relapse or metastatic, contralateral, or second cancer) survival at 5 and 10 years
Overall survival at 5 and 10 years
Toxicity according to CTCAE version 3.0
Lipid tolerance or cardiovascular or bone event
Quality of life according to MRS and SF36 questionnaires
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00673335
Brief Title
Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
Acronym
LIBER
Official Title
Prevention of Breast Cancer by Letrozole in Post-menopausal Women Carrying a BRCA1/BRCA2 Mutation
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 2008 (Actual)
Primary Completion Date
June 2019 (Actual)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UNICANCER
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
170 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment arm
Arm Type
Experimental
Arm Description
Letrozole, 1 tablet
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Comparator, 1 tablet
Intervention Type
Drug
Intervention Name(s)
letrozole
Other Intervention Name(s)
Femara
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Survival without contralateral or unilateral invasive breast cancer at 5 years (prior breast cancer)
Time Frame
2017
Title
Survival without invasive breast cancer at 5 years
Time Frame
2017
Secondary Outcome Measure Information:
Title
Invasive cancer-free survival at 10 years
Time Frame
2022
Title
Breast cancer in situ-free survival at 5 and 10 years
Time Frame
2022
Title
Relapse-free (local or metastatic disease) survival in patients with history of breast cancer at 5 and 10 years
Time Frame
2017 and 2022
Title
Second cancer-free survival at 5 and 10 years
Time Frame
2017 and 2022
Title
Event- free (local relapse or metastatic, contralateral, or second cancer) survival at 5 and 10 years
Time Frame
2017 and 2022
Title
Overall survival at 5 and 10 years
Time Frame
2017 and 2022
Title
Toxicity according to CTCAE version 3.0
Time Frame
2017 and 2022
Title
Lipid tolerance or cardiovascular or bone event
Time Frame
2017 and 2022
Title
Quality of life according to MRS and SF36 questionnaires
Time Frame
2017 and 2022
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility 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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pascal Pujol, MD
Organizational Affiliation
Hopital Arnaud de Villeneuve
Official's Role
Study Chair
Facility Information:
Facility Name
Institut Sainte Catherine
City
Avignon
ZIP/Postal Code
84082
Country
France
Facility Name
Centre Regional Francois Baclesse
City
Caen
ZIP/Postal Code
14076
Country
France
Facility Name
Centre Jean Perrin
City
Clermont-Ferrand
ZIP/Postal Code
63011
Country
France
Facility Name
Centre Oscar Lambret
City
Lille
ZIP/Postal Code
59020
Country
France
Facility Name
Centre Leon Berard
City
Lyon
ZIP/Postal Code
69373
Country
France
Facility Name
Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
City
Marseille
ZIP/Postal Code
13273
Country
France
Facility Name
Hopital Arnaud de Villeneuve
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
Centre Catherine de Sienne
City
Nantes
ZIP/Postal Code
02
Country
France
Facility Name
Centre Antoine Lacassagne
City
Nice
ZIP/Postal Code
06189
Country
France
Facility Name
Centre Hospitalier General de Niort
City
Niort
ZIP/Postal Code
79021
Country
France
Facility Name
Hopital Saint Michel
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Hotel Dieu de Paris
City
Paris
ZIP/Postal Code
75181
Country
France
Facility Name
Institut Curie Hopital
City
Paris
ZIP/Postal Code
75248
Country
France
Facility Name
CHU Poitiers
City
Poitiers
ZIP/Postal Code
86021
Country
France
Facility Name
Polyclinique De Courlancy
City
Reims
ZIP/Postal Code
F-51100
Country
France
Facility Name
Centre Eugene Marquis
City
Rennes
ZIP/Postal Code
35042
Country
France
Facility Name
Centre Henri Becquerel
City
Rouen
ZIP/Postal Code
76038
Country
France
Facility Name
Centre Rene Huguenin
City
Saint Cloud
ZIP/Postal Code
92211
Country
France
Facility Name
CHU Sainte-Etienne - Hopital Nord
City
Saint-Étienne
ZIP/Postal Code
42055
Country
France
Facility Name
Centre Paul Strauss
City
Strasbourg
ZIP/Postal Code
67065
Country
France
Facility Name
Institut Claudius Regaud
City
Toulouse
ZIP/Postal Code
31052
Country
France
Facility Name
Centre Alexis Vautrin
City
Vandoeuvre-les-Nancy
ZIP/Postal Code
54511
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
F-94805
Country
France
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.
IPD Sharing 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.
IPD Sharing 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.
Citations:
PubMed Identifier
22076253
Citation
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.
Results Reference
background
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, 2009.
Results Reference
result
Learn more about this trial
Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
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