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

Sponsor

UNICANCER (Other)

Overall Status

Completed

CT.gov ID

NCT00629616

Collaborator

(none)

116

Enrollment

Locations

Arms

126

Actual Duration (Months)

19.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: anastrozole Drug: fulvestrant	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

116 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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.

Actual Study Start Date :

Oct 1, 2007

Actual Primary Completion Date :

Jun 1, 2015

Actual Study Completion Date :

Apr 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A Anastrozole	Drug: anastrozole 1 mg/day for either 4 months or 6 months depending on the clinical evaluation
Experimental: Arm B Fulvestrant	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

Arm

Intervention/Treatment

Experimental: Arm A

Anastrozole

Drug: anastrozole

1 mg/day for either 4 months or 6 months depending on the clinical evaluation

Experimental: Arm B

Fulvestrant

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

Outcome Measures

Primary Outcome Measures

Clinical tumor response as assessed by RECIST criteria [6 months]

Secondary Outcome Measures

Breast surgery conservation rate [Post surgery]
Histological tumor response as assessed by the Sataloff scale [Post surgery]
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 [3 years]
Relapse-free survival rate [3 years]
Event-free survival rate [3 years]
Overall survival rate [3 years]
Toxicity as assessed by NCI CTCAE v3.0 [During neoadjuvant treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Centre Jean Perrin	Clermont-Ferrand	France	63011
2	Hopital Dupuytren	Limoges Cedex	France	87042
3	Institut Curie Hopital	Paris	France	75248
4	Centre Eugene Marquis	Rennes	France	35042
5	Centre Rene Huguenin	Saint-Cloud	France	92210
6	Institut Gustave Roussy	Villejuif	France	F-94805