Anastrozole or Fulvestrant in Treating Postmenopausal Patients With Breast Cancer

NCT ID: NCT00871858

Last Updated: 2021-02-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-18
• Study Completion Date: 2018-07-02

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A (ANA)

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

Group Type: ACTIVE_COMPARATOR

anastrozole

Intervention Type: DRUG

Given orally

Arm B (FULV)

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

Group Type: EXPERIMENTAL

fulvestrant

Intervention Type: DRUG

Given intramuscularly

Interventions

anastrozole

Given orally

Intervention Type: DRUG

fulvestrant

Given intramuscularly

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute, France

OTHER_GOV

Sponsor Role: collaborator

Institut Bergonié

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Louis Mauriac, MD

Role: PRINCIPAL_INVESTIGATOR

Institut Bergonié

Locations

Institut Bergonie

Bordeaux, , France

Countries

France

References

Quenel-Tueux N, Debled M, Rudewicz J, MacGrogan G, Pulido M, Mauriac L, Dalenc F, Bachelot T, Lortal B, Breton-Callu C, Madranges N, de Lara CT, Fournier M, Bonnefoi H, Soueidan H, Nikolski M, Gros A, Daly C, Wood H, Rabbitts P, Iggo R. Clinical and genomic analysis of a randomised phase II study evaluating anastrozole and fulvestrant in postmenopausal patients treated for large operable or locally advanced hormone-receptor-positive breast cancer. Br J Cancer. 2015 Aug 11;113(4):585-94. doi: 10.1038/bjc.2015.247. Epub 2015 Jul 14.

Reference Type: RESULT

PMID: 26171933 (View on PubMed)

Lerebours F, Pulido M, Fourme E, Debled M, Becette V, Bonnefoi H, Rivera S, MacGrogan G, Mouret-Reynier MA, de Lara CT, Pierga JY, Breton-Callu C, Venat-Bouvet L, Mathoulin-Pelissier S, de la Motte Rouge T, Dalenc F, Sigal B, Bachelot T, Lemonnier J, Quenel-Tueux N. Predictive factors of 5-year relapse-free survival in HR+/HER2- breast cancer patients treated with neoadjuvant endocrine therapy: pooled analysis of two phase 2 trials. Br J Cancer. 2020 Mar;122(6):759-765. doi: 10.1038/s41416-020-0733-x. Epub 2020 Jan 31.

Reference Type: DERIVED

PMID: 32001832 (View on PubMed)

Other Identifiers

2007-004216-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CDR0000633329

Identifier Type: -

Identifier Source: org_study_id