Clinical trial NCT00871858
Conditions: Breast Cancer
Keywords: stage II breast cancer stage IIIA breast cancer stage IIIB breast cancer estrogen receptor-positive breast cancer progesterone receptor-positive breast cancer
Sponsor: Institut Bergonié
Start date: 2008-03-18; Completion date: 2018-07-02
Enrollment: 120 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: Patients receive oral anastrozole as 1 mg film-coated tablets, once daily for 6 months. arm 2: Patients receive fulvestrant intramuscularly ( 250 mg/5 ml solution) on days 1, 14, and 28 and then once a month thereafter until 6 months.
Interventions: intervention 1: anastrozole intervention 2: fulvestrant
Intervention descriptions: intervention 1: Given orally intervention 2: Given intramuscularly

Protocol documents: