Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation - Full Text View

Sponsored by:	Federation Nationale des Centres de Lutte Contre le Cancer
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00673335

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 Other: laboratory biomarker analysis Other: pharmacogenomic studies	Phase III

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Ovarian Cancer

Drug Information available for: Letrozole

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double-Blind, Placebo Control
Official Title:	Prevention of Breast Cancer by Letrozole in Post-Menopausal Women Carrying a BRCA ½ Mutation

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	724
Study Start Date:	May 2008
Estimated Primary Completion Date:	February 2015 (Final data collection date for primary outcome measure)

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
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

Contacts and Locations

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

Locations

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

Sponsors and Collaborators

Federation Nationale des Centres de Lutte Contre le Cancer

Investigators

Investigator:

Pascal Pujol, MD

Hopital Arnaud de Villeneuve

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000586472, FNCLCC-ONCO-03/0701, EU-20806, NOVARTIS-FNCLCC-ONCO 03/0701
Study First Received:	May 6, 2008
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00673335 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Ovarian Neoplasms
Skin Diseases
Gonadal Disorders
Genital Neoplasms, Female
Breast Neoplasms
Endocrine System Diseases
Letrozole
Urogenital Neoplasms

Ovarian Diseases
Genital Diseases, Female
Ovarian Cancer
Endocrinopathy
Aromatase Inhibitors
Breast Diseases
Menopause
Endocrine Gland Neoplasms

Additional relevant MeSH terms:

Ovarian Neoplasms
Molecular Mechanisms of Pharmacological Action
Skin Diseases
Antineoplastic Agents
Gonadal Disorders
Genital Neoplasms, Female
Breast Neoplasms
Endocrine System Diseases
Enzyme Inhibitors
Letrozole
Urogenital Neoplasms

Ovarian Diseases
Pharmacologic Actions
Adnexal Diseases
Genital Diseases, Female
Neoplasms
Neoplasms by Site
Therapeutic Uses
Aromatase Inhibitors
Breast Diseases
Endocrine Gland Neoplasms

ClinicalTrials.gov processed this record on May 07, 2009