Efficacy of Anastrozole and Fulvestrant in Patients With ER Positive, HER2 Negative, Operable Breast Cancer (NIMFEA)

Tracking Information
First Submitted Date ICMJE	March 5, 2008
First Posted Date ICMJE	March 6, 2008
Last Update Posted Date	August 6, 2014
Study Start Date ICMJE	August 2007
Estimated Primary Completion Date	September 2016 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: July 20, 2012)	Clinical tumor response as assessed by RECIST criteria [ Time Frame: 6 months ]
Original Primary Outcome Measures ICMJE; (submitted: March 5, 2008)	Clinical tumor response at 6 months as assessed by RECIST criteria
Change History	Complete list of historical versions of study NCT00629616 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: July 20, 2012)	Breast surgery conservation rate [ Time Frame: Post surgery ]; Histological tumor response as assessed by the Sataloff scale [ Time Frame: Post surgery ]; Tumor response as assessed by mammography, ultrasonography (RECIST criteria), and MRI [ Time Frame: at baseline, after the first month of treatment, and then before surgery ]; Biological prognosis and predictive response factors [ Time Frame: 3 years ]; Relapse-free survival rate [ Time Frame: 3 years ]; Event-free survival rate [ Time Frame: 3 years ]; Overall survival rate [ Time Frame: 3 years ]; Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: During neoadjuvant treatment ]
Original Secondary Outcome Measures ICMJE; (submitted: March 5, 2008)	Breast surgery conservation rate; Histological tumor response as assessed by the Sataloff scale; Tumor response as assessed by mammography, ultrasonography (RECIST criteria), and MRI at baseline, after the first month of treatment, and then before surgery; Biological prognosis and predictive response factors; Relapse-free survival rate at 3 years; Event-free survival rate at 3 years; Overall survival rate at 3 years; Toxicity as assessed by NCI CTCAE v3.0
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Efficacy of Anastrozole and Fulvestrant in Patients With ER Positive, HER2 Negative, Operable Breast Cancer
Official Title ICMJE	A Randomized Multicenter Phase II Study Identifying Hormone Sensitivity Profiles and Evaluating the Efficacy of Anastrozole and Fulvestrant in the Neo-adjuvant Treatment of Operable Breast Cancer in Postmenopausal Women.
Brief Summary	RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using anastrozole or fulvestrant may fight breast cancer by lowering the amount of estrogen the body makes or by blocking the use of estrogen by the tumor cells. Giving hormone therapy before surgery may be an effective treatment for breast cancer. It is not yet known whether anastrozole is more effective than fulvestrant when given before surgery in treating women with breast cancer. PURPOSE: This randomized phase II trial is studying anastrozole to see how well it works compared with fulvestrant in treating postmenopausal women with stage II or stage III breast cancer that can be removed by surgery.
Detailed Description	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.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Breast Cancer
Intervention ICMJE	Drug: anastrozole 1 mg/day for either 4 months or 6 months depending on the clinical evaluation; Drug: fulvestrant 500mg at day 1, day 15 and day 29 500mg every 28 days for either 4 months or 6 months depending on the clinical evaluation
Study Arms	Experimental: Arm A Anastrozole Intervention: Drug: anastrozole; Experimental: Arm B Fulvestrant Intervention: Drug: fulvestrant
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Unknown status
Actual Enrollment ICMJE; (submitted: March 5, 2008)	116
Original Enrollment ICMJE	Same as current
Estimated Study Completion Date	September 2016
Estimated Primary Completion Date	September 2016 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: Female
Ages	Child, Adult, Senior
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	France
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00629616
Other Study ID Numbers ICMJE	CARMINA02; CARMINA-02/0609 ( Other Identifier: UNICANCER ); 2006-006409-10 ( EudraCT Number ); NIMFEA ( Other Identifier: UNICANCER )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	UNICANCER
Study Sponsor ICMJE	UNICANCER
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Florence Lerebours, MD Institut Curie
PRS Account	UNICANCER
Verification Date	August 2014
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP