Fulvestrant (Faslodex) + Anastrozole (Arimidex) vs Anastrozole

March 9, 2023 updated by: Spanish Breast Cancer Research Group

Phase III Trial Comparing Efficacy and Tolerance of Fulvestrant for 3 Years (y) Combined With Anastrozole 5 y Versus Anastrozole 5 y as Adjuvant Hormonotherapy in Postmenopausal With Early Breast Cancer and Positive Hormone Receptors

Postmenopausal women with hormone receptor positive and negative Her2 tumours.

Before randomization, the patients will be stratified according to the center, positive nodes (0 vs. 1-3 vs. ≥4), previous chemotherapy (yes vs no) and hormonal receptors status.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

It is expected that disease-free survival for patients receiving Anastrozole alone for 5 years will be up to 90%. An increase of 3% in disease-free survival (DFS) is expected in the arm of Fulvestrant plus Anastrozole, i.e a DFS of up to 93%. They will be required 1358 patients per treatment group (i.e, 2716 patients in total) to give 80% power, alfa bilateral 0.05, and OR 0.6888. Assuming 5% screening failures 2852 patients are required to enter the study. In Jun-2010 the recruitment was stopped due to lack of support of the financier based on the result of Faslodex® and Arimidex® in Combination Trial (FACT-trial), comparing Fulvestrant + Anastrozole vs Anastrozole alone in 1st relapse showed no difference in time to progression at more than 40 months follow-up.

Study Type

Interventional

Enrollment (Actual)

870

Phase

  • Phase 3

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

  • Spain
      • A Coruña, Spain, 15006
        • Complejo Hospitalario Universitario A Coruña
      • A Coruña, Spain, 15009
        • Centro Oncológico de Galicia
      • Almería, Spain, 04009
        • Complejo Hospitalario Torrecárdenas
      • Barcelona, Spain, 08025
        • Hospital de la Santa Creu i Sant Pau
      • Barcelona, Spain, 08036
        • Hospital Clinic i Provincial de Barcelona
      • Cadiz, Spain, 11009
        • Hospital Universitario Puerta Del Mar
      • Córdoba, Spain, 14004
        • Hospital Universitario Reina Sofia
      • Girona, Spain, 17007
        • HOSPITAL UNIVERSITARI DE GIRONA DR. JOSEP TRUETA (ICO de Girona)
      • Granada, Spain, 18012
        • Hospital Universitario San Cecilio
      • Guadalajara, Spain, 19002
        • Hospital General Universitario de Guadalajara
      • Huelva, Spain, 21005
        • Hospital Juan Ramón Jimenez
      • Jaén, Spain, 23007
        • Complejo Hospitalario de Jaen
      • Lleida, Spain, 25198
        • Hospital Universitario Arnau de Vilanova de Lleida
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon y Cajal
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Maranon
      • Madrid, Spain, 28040
        • Hospital Clínico Universitario San Carlos
      • Madrid, Spain, 28050
        • CENTRO INTEGRAL ONCOLÓGICO CLARA CAMPAL (Hospital Madrid Norte Sanchinarro)
      • Malaga, Spain, 29010
        • Hospital Regional Universitario Carlos Haya
      • Malaga, Spain, 29010
        • Hospital Clinico Universitario Virgen de la Victoria
      • Murcia, Spain, 30008
        • Hospital General Universitario Morales Meseguer
      • Santa Cruz de Tenerife, Spain, 38010
        • Hospital Universitario Nuestra Señora de Candelaria
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio
      • Toledo, Spain, 45004
        • Hospital Virgen de la Salud
      • Valencia, Spain, 46009
        • Instituto Valenciano de Oncología
      • Valencia, Spain, 46014
        • Consorcio Hospital General Universitario de Valencia
      • Valencia, Spain, 46015
        • Hospital Clínico Universitario de Valencia
      • Valencia, Spain, 46015
        • Hospital Universitario Arnau de Vilanova de Valencia
      • Zaragoza, Spain, 50009
        • Hospital Universitario Miguel Servet
    • Alicante
      • Alcoy, Alicante, Spain, 03804
        • Hospital Universitario Virgen de los Lirios
      • Elche, Alicante, Spain, 03203
        • Hospital General Universitario de Elche
      • Elda, Alicante, Spain, 03600
        • Hospital General Universitario de Elda
      • Torrevieja, Alicante, Spain, 03180
        • Hospital Usp San Jaime
      • Torrevieja, Alicante, Spain, 03186
        • Hospital de Torrevieja Salud Ute
    • Asturias
      • Avilés, Asturias, Spain, 33400
        • Hospital San Agustín de Avilés
    • Barcelona
      • Badalona, Barcelona, Spain, 08916
        • Hospital Universitari Germans Trias I Pujol
      • Badalona, Barcelona, Spain, 08911
        • Hospital Municipal de Badalona
      • Granollers, Barcelona, Spain, 08402
        • Hospital General de Granollers
      • L'hospitalet de Llobregat, Barcelona, Spain, 08907
        • Institut Catala d'Oncologia L'Hospitalet
      • Sabadell, Barcelona, Spain, 08208
        • Corporacio Sanitaria Parc Tauli
      • Terrassa, Barcelona, Spain, 08227
        • Consorci Sanitari de Terrassa
      • Terrassa, Barcelona, Spain, 08221
        • Hospital Mutua De Terrassa
    • Cantabria
      • Santander, Cantabria, Spain, 39008
        • Hospital Universitario Marques de Valdecilla
    • Castellón
      • Castellón de La Plana, Castellón, Spain, 12002
        • Consorcio Hospitalario Provincial de Castellon
    • Guipúzcoa
      • Donostia-san Sebastián, Guipúzcoa, Spain, 20014
        • Hospital Donostia
      • Donostia-san Sebastián, Guipúzcoa, Spain, 20014
        • Onkologikoa
    • Huesca
      • Barbastro, Huesca, Spain, 22300
        • Hospital de Barbastro
    • LAS Palmas
      • Las Palmas de Gran Canaria, LAS Palmas, Spain, 35016
        • Complejo hospitalario Universitario Insular-Materno Infantil
    • Madrid
      • Alcorcón, Madrid, Spain, 28922
        • Hospital Universitario Fundacion Alcorcon
    • Santa CRUZ DE Tenerife
      • La Laguna, Santa CRUZ DE Tenerife, Spain, 38320
        • Hospital Universitario de Canarias
    • Sevilla
      • Dos Hermanas, Sevilla, Spain, 41700
        • Hospital Universitario de Valme
    • Valencia
      • Sagunto, Valencia, Spain, 46520
        • Hospital de Sagunto
      • Xátiva, Valencia, Spain, 46800
        • Hospital Lluis Alcanyis
    • Vizcaya
      • Bilbao, Vizcaya, Spain, 48013
        • Hospital de Basurto

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion criteria:

  1. Histological documentation of breast cancer.

  2. Stage I, II, IIIA and IIIC* invasive breast cancer. One of these two characteristics must be fulfilled:

    • N+
    • T > 1cm *Eligible patients T1-T3 and pN3a (patients with metastasis in infraclavicular nodes would not be eligible)

  3. Local treatment with curative intention:

    • mastectomy or tumour excision with free margins + radiotherapy
    • axillary lymphadenectomy or sentinel node biopsy
  4. Positive hormone receptors (Estrogen Receptor [ER]+ and/or Progesterone Receptor [PR]+) in primary tumour tissue as measured by a central laboratory
  5. Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancer, defined as immunohistochemistry (IHC) 0 or 1+ or negative fluorescence in situ hybridization (FISH) (in the event of IHC 2+ or 3+)

  6. Postmenopausal women, defined as women meeting any of the following criteria:

    • Age ≥ 60 years
    • Age ≥ 45 years with amenorrhea ≥ 12 months in the moment of breast cancer diagnosis and an intact uterus
    • Prior bilateral ovariectomy
    • In case previous hysterectomy, follicle stimulating hormone (FSH) and estradiol levels within the postmenopausal range (using local laboratory ranges)* * In patients previously treated with a luteinizing hormone releasing hormone (LH-RH) analogue, the last extended release formulation should have been administered more than 6 months before randomisation, and menses must not have reappeared.
  7. A World Health Organization (WHO) performance status of 0, 1, or 2.
  8. Age > 18 years

Exclusion criteria:

  1. Presence of metastatic disease or bilateral invasive cancer
  2. ER and Progesterone Receptor (PR) negative breast cancer
  3. HER2-positive breast cancer, defined as FISH+
  4. Treatment with a non-approved or experimental drug within 4 months of randomisation
  5. Current malignancy or previous malignancy in the past 5 years (other that breast cancer or basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix)
  6. Pregnant or nursing patients

  7. Any of the following laboratory values within 3 months of randomisation:

    • Platelets < 100 x 109/L

    • Total bilirubin > 1.5 x Upper limit of reference range (ULRR)**

      ** Patients with documented Gilbert syndrome may be included in this trial

    • Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) > 2.5 x ULRR
    • A history of:
    • hemorrhagic diathesis (i.e. Disseminated Intravascular Coagulation [DIC], coagulation factor deficiency) or
    • long-term anticoagulant treatment (except for anti-platelet aggregants and low-dose warfarin; see section 3.7)
  8. A history of hypersensitivity to the active ingredient or inactive excipients of fulvestrant, aromatase inhibitors, or castor oil
  9. Any concomitant severe disease advising against patient participation in the trial o that may jeopardize compliance with the trial protocol, such as uncontrolled heart disease, uncontrolled diabetes mellitus, or uncontrolled severe infections
  10. Hormone replacement therapy

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
Experimental: Fulvestrant + Anastrozole
Fulvestrant loading dose regimen will consist of two 5 ml intramuscular injections on day 0 (500 mg), 250 mg single injection on days 14 and 28, and 250 mg single injection every 28 days thereafter for 3 years plus Anastrozole 1 mg PO once daily for 5 years
Drug: Fulvestrant
500 mg Im Fulvestrant day 0, 250 mg days 14 and 28(charge dose); later 250 mg each 28 days during 3 years plus 1 mg oral Anastrozole per day during 5 years.
Other Names:
  • Faslodex
Drug: Anastrozole
1 mg oral Anastrozole per day during 5 years.
Other Names:
  • Arimidex
Active Comparator: Anastrozole
Anastrozole 1 mg will be administered orally as one tablet daily for 5 years.
Drug: Anastrozole
1 mg oral Anastrozole per day during 5 years.
Other Names:
  • Arimidex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Free Survival (DFS) Events
Time Frame: Up to 5 years

Disease-free survival (DFS) has been evaluated in patients treated with Fulvestrant for 3 years and Anastrozole for 5 years as compared to DFS in patients treated with anastrozole for 5 years.

DFS event is defined as the evidence of local and/or distant recurrence, new primary breast tumour, or death from any cause.
Up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Breast Cancer Specific Survival (BCsS) Events
Time Frame: Up to 5 years

BCsS events has been evaluated in patients treated with Fulvestrant for 3 years and Anastrozole for 5 years as compared to BCsS in patients treated with anastrozole for 5 years.

BCsS event is defined as the death from breast cancer.
Up to 5 years
Overall Survival (OS) Event
Time Frame: Up to 5 years

OS event has been evaluated in patients treated with Fulvestrant for 3 years and Anastrozole for 5 years as compared to DFS in patients treated with anastrozole for 5 years.

OS event is defined as the death from any cause.
Up to 5 years
Time to Recurrence (TR) Event
Time Frame: Up to 5 years

TR event has been evaluated in patients treated with Fulvestrant for 3 years and Anastrozole for 5 years as compared to DFS in patients treated with anastrozole for 5 years.

TR event is defined as the evidence of breast cancer recurrence (local and/or distant recurrence of breast cancer, does not include second primary malignancies or deaths from any cause).
Up to 5 years

Collaborators and Investigators

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

Sponsor

Spanish Breast Cancer Research Group

Collaborators

AstraZeneca

Investigators

  • Study Director: Study Director, Centro Oncológico de Galicia

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)

November 1, 2007

Primary Completion (Actual)

July 1, 2016

Study Completion (Actual)

July 1, 2016

Study Registration Dates

First Submitted

October 11, 2007

First Submitted That Met QC Criteria

October 11, 2007

First Posted (Estimate)

October 12, 2007

Study Record Updates

Last Update Posted (Estimate)

March 10, 2023

Last Update Submitted That Met QC Criteria

March 9, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GEICAM/2006-10
  • 2007-003417-14 (EudraCT Number)

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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