Anastrozole or Fulvestrant in Treating Postmenopausal Patients With Breast Cancer (HORGEN)

Institut Bergonié

Status and phase: Completed; Phase 2

Conditions: Breast Cancer

Treatments: Drug: anastrozole; Drug: fulvestrant

Study type: Interventional

Funder types: Other

Identifiers

NCT00871858

CDR0000633329

2007-004216-31 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 120 patients

Sex: Female

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive breast cancer, meeting 1 of the following criteria:

  • SBR grade I-II disease (patients < 65 years of age)
  • SBR grade I-III disease (patients > 65 years of age)

• T2 (2-5 cm), T3, or T4B, and N0-1 disease

• No metastatic disease

• Breast lesion not amenable to breast-conserving resection

• No inflammatory breast cancer

• No prior breast cancer

• Hormone receptor status:

  • Estrogen receptor- and/or progesterone receptor-positive

PATIENT CHARACTERISTICS:

• Postmenopausal
• No other cancer within the past 5 years except for adequately treated skin carcinoma or carcinoma in situ of the cervix
• No contraindication to anti-hormonal treatment
• No psychological, familial, social, or geographical reasons that would preclude follow up

PRIOR CONCURRENT THERAPY:

• At least 8 days since prior hormone replacement therapy
• No concurrent anti-vitamin K treatment

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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120 participants in 2 patient groups

Arm A (ANA)

Active Comparator group

Description:

Patients receive oral anastrozole as 1 mg film-coated tablets, once daily for 6 months.

Treatment:

Drug: anastrozole

Arm B (FULV)

Experimental group

Description:

Patients receive fulvestrant intramuscularly ( 250 mg/5 ml solution) on days 1, 14, and 28 and then once a month thereafter until 6 months.

Treatment:

Drug: fulvestrant