brca1 Mutation CarrierPhase 3LIBERNCT00673335
Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
A Phase 3 study testing letrozole in people with brca1 Mutation Carrier and brca2 Mutation Carrier, run by UNICANCER at 23 sites in France.
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. Read more about this study
- Who is it for?
- Ages 40 to 69 years, women only
- Conditions the study is for
- brca1 Mutation Carrier, brca2 Mutation Carrier, Breast Cancer
- What is being tested?
- letrozole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 170 participants
- Where
- 23 sitesFrance
- Study dates
- May 2008to Dec 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 69 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
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- 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
Trial locations and contacts
23 sites in 1 country.
23 sites in 1 country
France23 sites
Institut Sainte Catherine
Avignon, 84082
Centre Regional Francois Baclesse
Caen, 14076
Centre Jean Perrin
Clermont-Ferrand, 63011
Centre Oscar Lambret
Lille, 59020
Centre Leon Berard
Lyon, 69373
Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
Marseille, 13273
Hopital Arnaud de Villeneuve
Montpellier, 34295
Centre Catherine de Sienne
Nantes, 02
Centre Antoine Lacassagne
Nice, 06189
Centre Hospitalier General de Niort
Niort, 79021
Hopital Saint Michel
Paris, 75015
Hotel Dieu de Paris
Paris, 75181
Institut Curie Hopital
Paris, 75248
CHU Poitiers
Poitiers, 86021
Polyclinique De Courlancy
Reims, F-51100
Centre Eugene Marquis
Rennes, 35042
Centre Henri Becquerel
Rouen, 76038
Centre Rene Huguenin
Saint-Cloud, 92211
CHU Sainte-Etienne - Hopital Nord
Saint-Etienne, 42055
Centre Paul Strauss
Strasbourg, 67065
Institut Claudius Regaud
Toulouse, 31052
Centre Alexis Vautrin
Vandœuvre-lès-Nancy, 54511
Institut Gustave Roussy
Villejuif, F-94805
About this study
Official title: Prevention of Breast Cancer by Letrozole in Post-menopausal Women Carrying a BRCA1/BRCA2 Mutation
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.
Read the 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)
- Being tested
- letrozole, Placebo
- Keywords
- breast cancer, hereditary breast/ovarian cancer (BRCA1, BRCA2), BRCA1 mutation carrier, BRCA2 mutation carrier
- Medical subject headings
- Breast Neoplasms, Hereditary Breast and Ovarian Cancer Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
letrozoleDrug
Also called Femara
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm | Experimental | Letrozole, 1 tablet Receives: Drug: letrozole |
| Placebo | Placebo comparator | Comparator, 1 tablet Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival without contralateral or unilateral invasive breast cancer at 5 years (prior breast cancer)
Measured: 2017
Survival without invasive breast cancer at 5 years
Measured: 2017
Secondary outcomes (9)
Invasive cancer-free survival at 10 years
Measured: 2022
Breast cancer in situ-free survival at 5 and 10 years
Measured: 2022
Relapse-free (local or metastatic disease) survival in patients with history of breast cancer at 5 and 10 years
Measured: 2017 and 2022
Second cancer-free survival at 5 and 10 years
Measured: 2017 and 2022
Event- free (local relapse or metastatic, contralateral, or second cancer) survival at 5 and 10 years
Measured: 2017 and 2022
Overall survival at 5 and 10 years
Measured: 2017 and 2022
Toxicity according to CTCAE version 3.0
Measured: 2017 and 2022
Lipid tolerance or cardiovascular or bone event
Measured: 2017 and 2022
Quality of life according to MRS and SF36 questionnaires
Measured: 2017 and 2022
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2008 (estimated)
- Study startMay 2008
- Primary completionJun 2019
- Study completionDec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for brca1 Mutation CarrierStudies of the same condition, open and under way.
- More trials run by UNICANCERThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 170 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNICANCER
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pascal Pujol, MD, Study chair, Hopital Arnaud de Villeneuve
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00673335
- Sponsor's protocol ID
- UC-0104/0701 - ONCO03
- Other IDs
- ONCO-03/0701, EU-20806, NOVARTIS-FNCLCC-ONCO 03/0701, 2007-000687-24
- Acronym
- LIBER
- Status last verified
- Jun 2024
- First submitted
- 6 May 2008
- Last updated
- 1 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 22076253Pujol 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.
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Breast Cancer by Letrozole in Post-menopausal Women Carrying a BRCA1/BRCA2 Mutation
- ClinicalTrials.gov ID
- NCT00673335
- Acronym / sponsor ID
- LIBER / UC-0104/0701 - ONCO03
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 170 participants (actual)
- Lead sponsor
- UNICANCERUniversity, hospital or other
- Study start
- May 2008 (actual)
- Primary completion
- Jun 2019 (actual)
- Study completion
- Dec 2023 (actual)
- First posted
- 7 May 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Drug: letrozoleLetrozole, 1 tablet |
| Placebo | Placebo comparator | Drug: PlaceboComparator, 1 tablet |
Who may qualify
- Ages
- 40 to 69 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Menopausal status as indicated by 1 of the following criteria:
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| letrozoleAlso: Femara | Drug | Treatment arm |
| Placebo | Drug | Placebo |
Primary outcome
Survival without contralateral or unilateral invasive breast cancer at 5 years (prior breast cancer)
Time frame: 2017
Survival without invasive breast cancer at 5 years
Time frame: 2017
9 secondary outcomes
Invasive cancer-free survival at 10 years
Time frame: 2022
Breast cancer in situ-free survival at 5 and 10 years
Time frame: 2022
Relapse-free (local or metastatic disease) survival in patients with history of breast cancer at 5 and 10 years
Time frame: 2017 and 2022
Second cancer-free survival at 5 and 10 years
Time frame: 2017 and 2022
Event- free (local relapse or metastatic, contralateral, or second cancer) survival at 5 and 10 years
Time frame: 2017 and 2022
Overall survival at 5 and 10 years
Time frame: 2017 and 2022
Toxicity according to CTCAE version 3.0
Time frame: 2017 and 2022
Lipid tolerance or cardiovascular or bone event
Time frame: 2017 and 2022
Quality of life according to MRS and SF36 questionnaires
Time frame: 2017 and 2022
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2024.
- Background: PubMed 22076253Pujol 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 publicationPujol 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pascal Pujol, MD study chair
Hopital Arnaud de Villeneuve
23 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing letrozole in people with brca1 Mutation Carrier and brca2 Mutation Carrier, run by UNICANCER at 23 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival without contralateral or unilateral invasive breast cancer at 5 years (prior breast cancer) (time frame: 2017). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00673335, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2024.