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

Breast Cancer Clinical Trial

— NIMFEA  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00629616
• Other study ID #: CARMINA02
• Secondary ID: CARMINA-02/06092
• Status: Completed
• Phase: Phase 2
• Start date: October 2007
• Est. completion date: April 2018

Study information

• Verified date: June 2021
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 116
• Est. completion date: April 2018
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• anastrozole
1 mg/day for either 4 months or 6 months depending on the clinical evaluation
• 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

Locations

Country	Name	City	State
France	Centre Jean Perrin	Clermont-Ferrand
France	Hopital Dupuytren	Limoges Cedex
France	Institut Curie Hopital	Paris
France	Centre Eugene Marquis	Rennes
France	Centre Rene Huguenin	Saint-Cloud
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
UNICANCER

Country where clinical trial is conducted

France, 

References & Publications (1)

Lerebours F, Rivera S, Mouret-Reynier MA, Alran S, Venat-Bouvet L, Kerbrat P, Salmon R, Becette V, Bourgier C, Cherel P, Boussion V, Balleyguier C, Thibault F, Lavau-Denes S, Nabholz JM, Sigal B, Trassard M, Mathieu MC, Martin AL, Lemonnier J, Mouret-Four — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical tumor response as assessed by RECIST criteria		6 months
Secondary	Breast surgery conservation rate		Post surgery
Secondary	Histological tumor response as assessed by the Sataloff scale		Post surgery
Secondary	Tumor response as assessed by mammography, ultrasonography (RECIST criteria), and MRI		at baseline, after the first month of treatment, and then before surgery
Secondary	Biological prognosis and predictive response factors		3 years
Secondary	Relapse-free survival rate		3 years
Secondary	Event-free survival rate		3 years
Secondary	Overall survival rate		3 years
Secondary	Toxicity as assessed by NCI CTCAE v3.0		During neoadjuvant treatment

External Links

•   Cancer . 2016 Oct;122(19):3032-40. doi: 10.1002/cncr.30143. Epub 2016 Jun 17.