Efficacy of Anastrozole and Fulvestrant in Patients With ER Positive, HER2 Negative, Operable Breast Cancer (NIMFEA)

June 4, 2021 updated by: UNICANCER

A Randomized Multicenter Phase II Study Identifying Hormone Sensitivity Profiles and Evaluating the Efficacy of Anastrozole and Fulvestrant in the Neo-adjuvant Treatment of Operable Breast Cancer in Postmenopausal Women.

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using anastrozole or fulvestrant may fight breast cancer by lowering the amount of estrogen the body makes or by blocking the use of estrogen by the tumor cells. Giving hormone therapy before surgery may be an effective treatment for breast cancer. It is not yet known whether anastrozole is more effective than fulvestrant when given before surgery in treating women with breast cancer.

PURPOSE: This randomized phase II trial is studying anastrozole to see how well it works compared with fulvestrant in treating postmenopausal women with stage II or stage III breast cancer that can be removed by surgery.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • To compare the clinical response rates (complete and partial responses) at 6 months in postmenopausal women with operable stage II or III breast cancer treated with neoadjuvant anastrozole vs fulvestrant.

Secondary

  • To compare the breast surgery conservation rate in patients treated with these drugs.
  • To correlate imaging findings by mammography, ultrasonography, and MRI with histological and clinical response in these patients and with sensitivity profile to these drugs.
  • To compare histological response in patients treated with these drugs.
  • To define criteria appropriate for neoadjuvant hormonal therapy.
  • To correlate baseline molecular characteristics and modifications during treatment with response in these patients.
  • To compare the tolerability of these drugs in these patients.
  • To compare the serum proteomic profile of patients treated with these drugs.
  • To correlate 3-year event-free and overall survival rates with clinical and histological response in these patients.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral anastrozole once daily for 4-6 months in the absence of clinical progression.
  • Arm II: Patients receive fulvestrant intramuscularly on days 1, 15, and 29 in the first month and then every 28 days in each subsequent month. Treatment continues for 4-6 months in the absence of clinical progression.

Patients in both arms then undergo surgery and radiotherapy according to institutional guidelines. Patients then receive adjuvant hormonal therapy for at least 5 years.

After completion of study therapy, patients are followed periodically for up to 3 years.

Study Type

Interventional

Enrollment (Actual)

116

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
      • Clermont-Ferrand, France, 63011
        • Centre Jean Perrin
      • Limoges Cedex, France, 87042
        • Hôpital Dupuytren
      • Paris, France, 75248
        • Institut Curie Hopital
      • Rennes, France, 35042
        • Centre Eugène Marquis
      • Saint-Cloud, France, 92210
        • Centre René Huguenin
      • Villejuif, France, F-94805
        • Institut Gustave Roussy

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

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed infiltrating breast adenocarcinoma

    • Large, operable tumor

    • Stage T2 (≥ 3 cm) or T3-T4 (excluding inflammatory disease), N0-N3, M0 disease

      • No bilateral inflammatory breast tumors (T4d [PEV-2 or PEV-3])
    • Elston-Ellis grade I or II and mitotic index 1 or 2 (if < 65 years of age)
  • At least 1 embedded and 1 frozen biopsy sample available
  • No multifocal or multicentric tumors for which breast conservation cannot be envisaged
  • No ErbB2-overexpressing tumors (HER2 3+ by IHC OR HER2 2+ by IHC and FISH positive)

  • Hormone receptor status:

    • Estrogen receptor and/or progesterone receptor positive tumor (> 10%) as assessed by IHC

PATIENT CHARACTERISTICS:

  • Female
  • Postmenopausal
  • ECOG performance status 0-2
  • ANC ≥ 2,000/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 10 g/dL
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)
  • Total bilirubin ≤ 1.25 times ULN
  • AST and ALT ≤ 1.5 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN
  • No other cancer within the past 10 years, except basal cell skin cancer or previously treated carcinoma in situ of the cervix

  • No uncontrolled cardiac pathology, including any of the following:

    • Angina pectoris
    • Congestive cardiac insufficiency
    • Myocardial infarction within the past 3 months
  • No known history of hemorrhagic diathesis
  • No known allergy to the study drugs or their excipients
  • No congenital galactosemia, glucose malabsorption syndrome, or lactase deficiency
  • No chronic somatic or psychiatric illness with pejorative prognosis
  • No geographical, social, or psychiatric condition that would preclude study compliance and follow-up schedule
  • No individual deprived of liberty or placed under the authority of a tutor

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy, hormonal therapy, or any targeted treatment for the breast tumor
  • At least 2 weeks since prior hormone replacement therapy for menopause
  • No concurrent long-term anticoagulation treatment
  • No concurrent participation on another therapeutic trial involving an experimental molecule

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
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Arm A
Anastrozole
Drug: anastrozole
1 mg/day for either 4 months or 6 months depending on the clinical evaluation
EXPERIMENTAL: Arm B
Fulvestrant
Drug: fulvestrant
500mg at day 1, day 15 and day 29 500mg every 28 days for either 4 months or 6 months depending on the clinical evaluation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Clinical tumor response as assessed by RECIST criteria
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival rate
Time Frame: 3 years
3 years
Breast surgery conservation rate
Time Frame: Post surgery
Post surgery
Histological tumor response as assessed by the Sataloff scale
Time Frame: Post surgery
Post surgery
Tumor response as assessed by mammography, ultrasonography (RECIST criteria), and MRI
Time Frame: at baseline, after the first month of treatment, and then before surgery
at baseline, after the first month of treatment, and then before surgery
Biological prognosis and predictive response factors
Time Frame: 3 years
3 years
Relapse-free survival rate
Time Frame: 3 years
3 years
Event-free survival rate
Time Frame: 3 years
3 years
Toxicity as assessed by NCI CTCAE v3.0
Time Frame: During neoadjuvant treatment
During neoadjuvant treatment

Collaborators and Investigators

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

Sponsor

UNICANCER

Investigators

  • Principal Investigator: Florence Lerebours, MD, Institut Curie

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

Helpful Links

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)

October 1, 2007

Primary Completion (ACTUAL)

June 1, 2015

Study Completion (ACTUAL)

April 1, 2018

Study Registration Dates

First Submitted

March 5, 2008

First Submitted That Met QC Criteria

March 5, 2008

First Posted (ESTIMATE)

March 6, 2008

Study Record Updates

Last Update Posted (ACTUAL)

June 9, 2021

Last Update Submitted That Met QC Criteria

June 4, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CARMINA02
  • CARMINA-02/0609 (OTHER: UNICANCER)
  • 2006-006409-10 (EUDRACT_NUMBER)
  • NIMFEA (OTHER: UNICANCER)

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.

Clinical Trials on Breast Cancer

Clinical Trials on anastrozole

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Guinea

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe