- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00871858
Anastrozole or Fulvestrant in Treating Postmenopausal Patients With Breast Cancer (HORGEN)
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
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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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-
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Bordeaux, France, 33076
- Institut Bergonie
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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.
|
Given orally
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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.
|
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:
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
Sponsor
Collaborators
Investigators
- Principal Investigator: Louis Mauriac, MD, Institut Bergonie
Publications and helpful links
General Publications
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Hormone Antagonists
- Aromatase Inhibitors
- Steroid Synthesis Inhibitors
- Estrogen Antagonists
- Estrogen Receptor Antagonists
- Fulvestrant
- Anastrozole
Other Study ID Numbers
- CDR0000633329
- 2007-004216-31 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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