Anastrozole or Fulvestrant in Treating Postmenopausal Patients With Breast Cancer

Phase 2

Completed

Conditions: Breast Cancer

Interventions: Drug: anastrozole
Drug: fulvestrant

Registration Number: NCT00871858

Lead Sponsor: Institut Bergonié

Brief Summary: RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using anastrozole may fight breast cancer by lowering the amount of estrogen the body makes. Fulvestrant may fight breast cancer by blocking the use of estrogen by the tumor cells. Given the lack of clinical data on fulvestrant in patients with large operable or locally advanced hormone-receptor-positive breast cancer, and the potential to identify differences in the mechanism of resistance using the neoadjuvant model,we decided to perform a multicentre randomised phase II clinical trial of anastrozole and fulvestrant.

PURPOSE: The aim of this study was to assess the efficacy of neoadjuvant anastrozole and fulvestrant treatment of large operable or locally advanced hormone-receptor-positive breast cancer not eligible for initial breast-conserving surgery, and to identify genomic changes occurring after treatment.

Detailed Description: OBJECTIVES:

Primary

* Evaluate clinical tumor response at 6 months in patients with hormone-sensitive non-metastatic breast cancer treated with neoadjuvant anastrozole and fulvestrant.

Secondary

* Evaluate tumor regression by mammography and ultrasound in these patients.

* Evaluate the rate of breast conservation at 6 months of treatment in these patients.

* Evaluate the tolerability of these regimens.

* Estimate the relapse-free survival at 5 years.

* Identify molecular signatures predictive of response in these patients.

* Identify genes implicated in response in these patients.

* Identify changes in mRNA splicing of genes involved in breast tumorigenesis.

OUTLINE: This is a non-comparative multicentre randomised phase II study in which patients from three French centres were randomly assigned in a 1 : 1 ratio to receive either anatrozole or fulvestrant.

All patients undergo biopsy at baseline. Patients are randomized between the two treatment arms.

* Arm I: Patients receive oral anastrozole once daily for 6 months.

* Arm II: Patients receive fulvestrant intramuscularly on days 1, 14, and 28 and then once a month at 2-6 months.

Within 8 days after completion of hormone therapy, all patients undergo surgical resection of the residual lesion followed by radiotherapy. Patients then receive oral anastrozole once daily for 5 years.

Tissue samples from biopsy and surgery are analyzed to assess molecular signatures and sensitivity to treatment, and to compare gene expression variation with response.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 120

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A (ANA)	anastrozole	Patients receive oral anastrozole as 1 mg film-coated tablets, once daily for 6 months.
Arm B (FULV)	fulvestrant	Patients receive fulvestrant intramuscularly ( 250 mg/5 ml solution) on days 1, 14, and 28 and then once a month thereafter until 6 months.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) Determined by Clinical Palpation	6 months	Objective response rate is defined as the rate of participants with partial or complete responses according to RECIST V1.0. Complete response is defined as the disappearance of all target lesions and partial response is defined as at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD (RECIST V1.0.).

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) Determined by Mammography	6 months	Objective response rate is defined as the rate of participants with partial or complete responses according to RECIST V1.0. Complete response is defined as the disappearance of all target lesions and partial response is defined as at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD (RECIST V1.0.).
Percentage of Participants With 5-year Relapse-Free Survival	5 years	Relapse-Free survival (RFS) is measured from the date of randomization to the date of the following events, whichever occurs first according to the DATECAN recommendations for breast cancer: * Invasive ipsilateral breast tumor recurrence/ progression ; * Local invasive recurrence/progression ; * Regional invasive recurrence/progression (N+: regional progression) ; * Appearance/Occurrence of Metastatic recurrence; * Death whatever the cause. Participants who did not experience events were censored at the date of last follow-up. RFS was estimated using the Kaplan-Meier method. No comparison test was performed between the two arms as this study is non-comparative.
Objective Response Rate (ORR) Determined by Ultrasound	6 months	Objective response rate is defined as the rate of participants with partial or complete responses according to RECIST V1.0. Complete response is defined as the disappearance of all target lesions and partial response is defined as at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD (RECIST V1.0.).
Rate of Breast-conserving Surgery	6 months	breast-conserving surgery concerns patients who did not undergo mastectomy.