Anastrozole or Fulvestrant in Treating Postmenopausal Patients With Breast Cancer

Breast Cancer Clinical Trial

— HORGEN  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00871858
• Other study ID #: CDR0000633329
• Secondary ID: 2007-004216-31
• Status: Completed
• Phase: Phase 2
• Start date: March 18, 2008
• Est. completion date: July 2, 2018

Study information

• Verified date: February 2021
• Source: Institut Bergonié
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: July 2, 2018
• Est. primary completion date: November 30, 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• anastrozole
Given orally
• fulvestrant
Given intramuscularly

Locations

Country	Name	City	State
France	Institut Bergonie	Bordeaux

Sponsors (2)

Lead Sponsor	Collaborator
Institut Bergonié	National Cancer Institute, France

Country where clinical trial is conducted

France, 

References & Publications (1)

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 genom — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) Determined by Clinical Palpation	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.).	6 months
Secondary	Objective Response Rate (ORR) Determined by Ultrasound	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.).	6 months
Secondary	Objective Response Rate (ORR) Determined by Mammography	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.).	6 months
Secondary	Rate of Breast-conserving Surgery	breast-conserving surgery concerns patients who did not undergo mastectomy.	6 months
Secondary	Percentage of Participants With 5-year Relapse-Free Survival	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.	5 years