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

February 3, 2021 updated by: Institut Bergonié

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.

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.

Study Overview

Status

Completed

Conditions

Intervention / 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.

Study Type

Interventional

Enrollment (Actual)

120

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Bordeaux, France, 33076
        • Institut Bergonie

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm A (ANA)
Patients receive oral anastrozole as 1 mg film-coated tablets, once daily for 6 months.
Drug: anastrozole
Given orally
Experimental: 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.
Drug: fulvestrant
Given intramuscularly

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) Determined by Clinical Palpation
Time Frame: 6 months

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) Determined by Ultrasound
Time Frame: 6 months

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
Objective Response Rate (ORR) Determined by Mammography
Time Frame: 6 months

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
Rate of Breast-conserving Surgery
Time Frame: 6 months
breast-conserving surgery concerns patients who did not undergo mastectomy.
6 months
Percentage of Participants With 5-year Relapse-Free Survival
Time Frame: 5 years

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut Bergonié

Collaborators

National Cancer Institute, France

Investigators

  • Principal Investigator: Louis Mauriac, MD, Institut Bergonie

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 18, 2008

Primary Completion (Actual)

November 30, 2013

Study Completion (Actual)

July 2, 2018

Study Registration Dates

First Submitted

March 27, 2009

First Submitted That Met QC Criteria

March 27, 2009

First Posted (Estimate)

March 30, 2009

Study Record Updates

Last Update Posted (Actual)

February 24, 2021

Last Update Submitted That Met QC Criteria

February 3, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000633329
  • 2007-004216-31 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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