Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

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.

Further Study Information

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 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

Trial Contact Information

Trial Lead Organizations/Sponsors

Federation Nationale des Centres de Lutte Contre le Cancer

Pascal Pujol

Study Chair

France
	Avignon
	Institut Sainte Catherine
		Contact Person	Ph: 33-490-27-61-61
	Caen
	Centre Regional Francois Baclesse
		Contact Person	Ph: 33-2-3145-5000
	Clermont-Ferrand
	Centre Jean Perrin
		Contact Person	Ph: 33-73-278-080
	Lille
	Centre Oscar Lambret
		Contact Person	Ph: 33-32-029-5959
	Lyon
	Centre Leon Berard
		Contact Person	Ph: 33-4-78-78-26-45
	Marseille
	Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
		Contact Person	Ph: 33-4-9122-3700
	Montpellier
	Hopital Arnaud de Villeneuve
		Contact Person	Ph: 33-467-335-875
	Nantes
	Centre Catherine de Sienne
		Contact Person	Ph: 33-40-02-28-272-000
	Nice
	Centre Antoine Lacassagne
		Contact Person	Ph: 33-49-203-1000
	Niort
	Centre Hospitalier General de Niort
		Contact Person	Ph: 33-5-4932-7979
	Paris
	Hopital Saint Michel
		Contact Person	Ph: 33-1-4045-6363
	Hotel Dieu de Paris
		Contact Person	Ph: 33-1-42-348-413
	Institut Curie Hopital
		Contact Person	Ph: 33-44-32-4000
	Poitiers
	CHU Poitiers
		Contact Person	Ph: 33-549-444-538
	Reims
	Polyclinique De Courlancy
		Contact Person	Ph: 33-3-2677-2777
	Rennes
	Centre Eugene Marquis
		Contact Person	Ph: 33-2-9925-3000
	Rouen
	Centre Henri Becquerel
		Contact Person	Ph: 33-2-3208-2222
	Saint Cloud
	Centre Rene Huguenin
		Contact Person	Ph: 33-1-47-111-515
	Sainte-Etienne
	CHU Sainte-Etienne - Hopital Nord
		Contact Person	Ph: 33-4-77-82-80-00
	Strasbourg
	Centre Paul Strauss
		Contact Person	Ph: 33-3-8825-2424
	Toulouse
	Institut Claudius Regaud
		Contact Person	Ph: 33-5-6142-4242
	Vandoeuvre-les-Nancy
	Centre Alexis Vautrin
		Contact Person	Ph: 33-3-8359-8400
	Villejuif
	Institut Gustave Roussy
		Contact Person	Ph: 33-1-4211-4339

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00673335
Information obtained from ClinicalTrials.gov on July 22, 2012

Back to Top