Clinical trial NCT00871858: Anastrozole or Fulvestrant in Treating Postmenopausal Patients With Breast Cancer
Official title: Response to Neoadjuvant Treatment With Anti-aromatase Anastrozole and Anti-estrogen Fulvestrant: a Randomized Phase II Study in Postmenopausal Patients With Hormone-sensitive Non-metastatic Breast Cancer and an Exploratory Study of Molecular Signatures of Response.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Institut Bergonié
Sponsor class: OTHER
Collaborators: name: National Cancer Institute, France
First posted: 2009-03-30
Enrollment: 120
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Objective Response Rate (ORR) Determined by Clinical Palpation
timeFrame: 6 months
Secondary outcomes:
measure: Objective Response Rate (ORR) Determined by Ultrasound
timeFrame: 6 months
measure: Objective Response Rate (ORR) Determined by Mammography
timeFrame: 6 months
measure: Rate of Breast-conserving Surgery
timeFrame: 6 months
measure: Percentage of Participants With 5-year Relapse-Free Survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Institut Bergonie
Study officials:
affiliation: Institut Bergonié
name: Louis Mauriac, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.