A Randomized Multicenter Phase II Study Identifying Hormonosensivity Profiles and Evaluating the Efficacy of Anastrozole and Fulvestrant in the Neo-adjuvant Treatment of Operable Breast Cancer in Postmenopausal Women.
N/A
N/A
Female
Breast Cancer
Trial Information
A Randomized Multicenter Phase II Study Identifying Hormonosensivity Profiles and Evaluating the Efficacy of Anastrozole and Fulvestrant in the Neo-adjuvant Treatment of Operable Breast Cancer in Postmenopausal Women.
OBJECTIVES:
Primary
- To compare the clinical response rates (complete and partial responses) at 6 months in
postmenopausal women with operable stage II or III breast cancer treated with
neoadjuvant anastrozole vs fulvestrant.
Secondary
- To compare the breast surgery conservation rate in patients treated with these drugs.
- To correlate imaging findings by mammography, ultrasonography, and MRI with
histological and clinical response in these patients and with sensitivity profile to
these drugs.
- To compare histological response in patients treated with these drugs.
- To define criteria appropriate for neoadjuvant hormonal therapy.
- To correlate baseline molecular characteristics and modifications during treatment with
response in these patients.
- To compare the tolerability of these drugs in these patients.
- To compare the serum proteomic profile of patients treated with these drugs.
- To correlate 3-year event-free and overall survival rates with clinical and
histological response in these patients.
OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral anastrozole once daily for 4-6 months in the absence of
clinical progression.
- Arm II: Patients receive fulvestrant intramuscularly on days 1, 15, and 29 in the first
month and then every 28 days in each subsequent month. Treatment continues for 4-6
months in the absence of clinical progression.
Patients in both arms then undergo surgery and radiotherapy according to institutional
guidelines. Patients then receive adjuvant hormonal therapy for at least 5 years.
After completion of study therapy, patients are followed periodically for up to 3 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed infiltrating breast adenocarcinoma
- Large, operable tumor
- Stage T2 (≥ 3 cm) or T3-T4 (excluding inflammatory disease), N0-N3, M0 disease
- No bilateral inflammatory breast tumors (T4d [PEV-2 or PEV-3])
- Elston-Ellis grade I or II and mitotic index 1 or 2 (if < 65 years of age)
- At least 1 embedded and 1 frozen biopsy sample available
- No multifocal or multicentric tumors for which breast conservation cannot be
envisaged
- No ErbB2-overexpressing tumors (HER2 3+ by IHC OR HER2 2+ by IHC and FISH positive)
- Hormone receptor status:
- Estrogen receptor and/or progesterone receptor positive tumor (> 10%) as
assessed by IHC
PATIENT CHARACTERISTICS:
- Female
- Postmenopausal
- ECOG performance status 0-2
- ANC ≥ 2,000/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 10 g/dL
- Creatinine ≤ 1.5 times upper limit of normal (ULN)
- Total bilirubin ≤ 1.25 times ULN
- AST and ALT ≤ 1.5 times ULN
- Alkaline phosphatase ≤ 2.5 times ULN
- No other cancer within the past 10 years, except basal cell skin cancer or previously
treated carcinoma in situ of the cervix
- No uncontrolled cardiac pathology, including any of the following:
- Angina pectoris
- Congestive cardiac insufficiency
- Myocardial infarction within the past 3 months
- No known history of hemorrhagic diathesis
- No known allergy to the study drugs or their excipients
- No congenital galactosemia, glucose malabsorption syndrome, or lactase deficiency
- No chronic somatic or psychiatric illness with pejorative prognosis
- No geographical, social, or psychiatric condition that would preclude study
compliance and follow-up schedule
- No individual deprived of liberty or placed under the authority of a tutor
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy, hormonal therapy, or any targeted treatment for the breast
tumor
- At least 2 weeks since prior hormone replacement therapy for menopause
- No concurrent long-term anticoagulation treatment
- No concurrent participation on another therapeutic trial involving an experimental
molecule
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Clinical tumor response as assessed by RECIST criteria
Outcome Time Frame:
6 months
Safety Issue:
No
Principal Investigator
Florence Lerebours, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Centre Rene Huguenin
Authority:
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Study ID:
CARMINA02
NCT ID:
NCT00629616
Start Date:
August 2007
Completion Date:
September 2014
Related Keywords:
- Breast Cancer
- stage II breast cancer
- stage IIIA breast cancer
- stage IIIB breast cancer
- stage IIIC breast cancer
- Breast Neoplasms
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