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

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

This study is currently recruiting participants.
Study NCT00673335 Information provided by National Cancer Institute (NCI)
First Received: May 6, 2008 Last Updated: February 6, 2009 History of Changes

Tracking Information
First Received Date ICMJE May 6, 2008
Last Updated Date February 6, 2009
Start Date ICMJE May 2008
Estimated Primary Completion Date February 2015 (final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE
(submitted: May 6, 2008) Survival without invasive breast cancer at 5 years (no prior history of breast cancer) [ Designated as safety issue: No ]
Survival without contralateral or unilateral invasive breast cancer at 5 years (prior breast cancer) [ Designated as safety issue: No ]

Original Primary Outcome Measures ICMJE Same as current
Change History Complete list of historical versions of study NCT00673335 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE
(submitted: May 6, 2008) Invasive cancer-free survival at 10 years [ Designated as safety issue: No ]
Breast cancer in situ-free survival at 5 and 10 years [ Designated as safety issue: No ]
Relapse-free (local or metastatic disease) survival in patients with history of breast cancer at 5 and 10 years [ Designated as safety issue: No ]
Second cancer-free survival at 5 and 10 years [ Designated as safety issue: No ]
Event- free (local relapse or metastatic, contralateral, or second cancer) survival at 5 and 10 years [ Designated as safety issue: No ]
Overall survival at 5 and 10 years [ Designated as safety issue: No ]
Toxicity according to CTC-AE version 3.0 [ Designated as safety issue: Yes ]
Lipid tolerance or cardiovascular or bone event [ Designated as safety issue: Yes ]
Quality of life according to MRS and SF36 [ Designated as safety issue: No ]

Original Secondary Outcome Measures ICMJE Same as current

Descriptive Information
Brief Title ICMJE Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
Official Title ICMJE Prevention of Breast Cancer by Letrozole in Post-Menopausal Women Carrying a BRCA ½ Mutation
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.

Study Phase Phase III
Study Type ICMJE Interventional
Study Design ICMJE Prevention, Randomized, Double-Blind, Placebo Control
Condition ICMJE brca1 Mutation Carrier
brca2 Mutation Carrier
Breast Cancer
Hereditary Breast/Ovarian Cancer (brca1, brca2)

Intervention ICMJE Drug: letrozole
Other: laboratory biomarker analysis
Other: pharmacogenomic studies

Study Arms / Comparison Groups
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status ICMJE Recruiting
Estimated Enrollment ICMJE 724
Completion Date
Estimated Primary Completion Date February 2015 (final data collection date for primary outcome measure)
Eligibility Criteria ICMJE 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
ECOG or WHO performance status 0-1
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

Gender Female
Ages 40 Years to 69 Years
Accepts Healthy Volunteers No
Contacts ICMJE
Location Countries ICMJE France

Administrative Information
NCT ID ICMJE NCT00673335
Responsible Party
Study ID Numbers ICMJE CDR0000586472, FNCLCC-ONCO-03/0701, EU-20806, NOVARTIS-FNCLCC-ONCO 03/0701
Study Sponsor ICMJE Federation Nationale des Centres de Lutte Contre le Cancer
Collaborators ICMJE
Investigators ICMJE Investigator: Pascal Pujol, MD Hopital Arnaud de Villeneuve

Information Provided By National Cancer Institute (NCI)
Verification Date August 2008