A partially-blind phase III randomised trial of fulvestrant (Faslodex™) with or without concomitant anastrozole (Arimidex™) compared with exemestane in post-menopausal women with oestrogen receptor (ER) positive locally advanced/metastatic breast cancer following progression on non-steroidal aromatase inhibitors

ISRCTN	ISRCTN44195747
DOI	https://doi.org/10.1186/ISRCTN44195747
EudraCT/CTIS number	2004-000093-30
ClinicalTrials.gov number	NCT00253422

Submission date: 27/06/2003
Registration date: 08/09/2003
Last edited: 18/12/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-hormone-therapy-for-advanced-breast-cancer

Study website

Contact information

Ms Gill Coombes
Scientific

Trial Manager
ICR Division of Clinical Studies (ICR-CTSU)
The Institute of Cancer Research
Sir Richard Doll Building
Cotswold Road
Sutton, Surrey
SM2 5NG
United Kingdom

Phone	+44 (0) 20 8722 4039
Email	sofea-icrctsu@icr.ac.uk

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	A partially-blind phase III randomised trial of fulvestrant (Faslodex™) with or without concomitant anastrozole (Arimidex™) compared with exemestane in post-menopausal women with oestrogen receptor (ER) positive locally advanced/metastatic breast cancer following progression on non-steroidal aromatase inhibitors
Study acronym	SoFEA
Study hypothesis	This randomised phase III trial is studying fulvestrant and anastrozole to see how well they work compared to fulvestrant and a placebo or exemestane alone in treating postmenopausal women with locally advanced or metastatic breast cancer.
Ethics approval(s)	Approved 18/09/2003, South West Multi Centre Research Ethic Committee (The Lescaze Offices, Dartington, TQ9 6JE, United Kingdom; +44 (0)1803 861947; cornwallandplymouth.rec@hra.nhs.uk), ref: MREC/03/6/77
Condition	Locally advanced/metastatic breast cancer
Intervention	The study will compare the progression-free survival of patients treated with Faslodex™ plus concomitant Arimidex™ (F+A) versus Faslodex™ (F) alone. All Faslodex™ treated patients will take either an Arimidex™ or an Arimidex™-placebo tablet once daily, and both patients and clinicians will be blinded to this treatment option (i.e., double-blind). A reference control arm will be included with the steroidal aromatase inhibitor exemestane (E) which is the current endocrine treatment of choice for such patients. 750 eligible patients will be randomised in a ratio of 1:1:1 to either: 1. Faslodex™ plus placebo or 2. Faslodex™ plus Arimidex™ or 3. Exemestane
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	Fulvestrant (Faslodex™), anastrozole (Arimidex™), exemestane
Primary outcome measure	Progression-free survival
Secondary outcome measures	1. Objective complete response (CR) and partial response (PR) rate 2. Duration of response 3. Clinical benefit (i.e., six-month CR, PR, and stable disease) rate 4. Duration of clinical benefit 5. Time to treatment failure 6. Overall survival 7. Tolerability
Overall study start date	01/03/2004
Overall study end date	01/01/2006

Eligibility

Participant type(s)	Patient
Age group	Mixed
Lower age limit	18 Years
Upper age limit	120 Years
Sex	Female
Target number of participants	750
Total final enrolment	698
Participant inclusion criteria	Patients with locally advanced/metastatic breast cancer who have progressed on the non-steroidal aromatase inhibitors (Arimidex™ or letrozole [Femara™]): 1. Female postmenopausal patients defined as: 1.1. Aged 60 years or over 1.2. Aged 45 to 59 with intact uterus and amenorrhoeic for at least 12 months 1.3. Any age having had a bilateral oophorectomy 2. Histologically or cytologically confirmed adenocarcinoma of the breast 3. Patients with original ER positive and/or progesterone (PgR) positive breast cancer which has relapsed or progressed during endocrine therapy with a single-agent non-steroidal aromatase inhibitor (NSAI) given either: 3.1. As adjuvant treatment where the patient received at least 12 months therapy, or 3.2. As first-line therapy for metastatic disease. Patients treated with an NSAI as first-line therapy must have had either an objective response (complete response [CR]/partial response [PR]), or stabilisation of disease for at least six months. 4. Measurable/evaluable sites of metastatic disease (response evaluation criteria in solid tumours [RECIST]) 5. World Health Organisation (WHO) performance status zero, one or two 6. Prior therapy permissible: 6.1. Tamoxifen given in the adjuvant or neo-adjuvant setting only 6.2. Prior chemotherapy in the adjuvant or neo-adjuvant setting 6.3. Prior chemotherapy as first-line treatment for metastatic breast cancer followed by NSAI alone for at least six months 6.4. Patients with bone-only metastases are eligible provided they have evaluable site of bone metastases that can be followed by skeletal survey or magnetic resonance imaging (MRI)/computed tomography (CT) scanning 6.5. Patients already established on bisphosphonate therapy for at least six months are eligible for the trial and may continue on bisphosphonates 7. Written informed consent and available for prolonged follow-up 8. Adequate haematological function defined by haemoglobin more than or equal to 10 g/dl, neutrophil count more than or equal to 1.5 x 10^9/l and platelets more than or equal to 100 x 10^9/l 9. Adequate hepatic function defined by aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 x upper limit of normal. Alkaline phosphatase less than or equal to 5 x upper limit of normal, unless bone metastases in the absence of liver disease. Renal function adequate defined by creatinine less than 175 mmol/l. 10. Life expectancy of more than three months and suitable for further endocrine therapy
Participant exclusion criteria	1. Patients whose primary breast cancer was classified as: 1.1. ER negative and PgR natural killer (NK) 1.2. ER negative/PgR negative 1.3. ER NK 2. Rapidly progressive visceral disease (i.e., lymphangitis carcinomatosa, diffuse hepatic involvement) 3. Bone-only metastases where lesions are not evaluable (i.e., patients with the same scan but no lytic disease on skeletal survey or MRI/CT) 4. Patients with malignancies (other than breast cancer) within the last five years, except for adequately treated in situ carcinoma of the cervix or basal cell/squamous cell carcinoma of the skin 5. Systemic corticosteroids for more than 15 days within the last four weeks 6. Investigational drugs given within the previous four weeks 7. Patients with thrombocytopaenia (platelets less than 100 x 10^9/l ) or on anti-coagulant therapy (contra-indicated due to risk of bleeding with intramuscular injection of Faslodex™)
Recruitment start date	01/03/2004
Recruitment end date	01/01/2006

Locations

Countries of recruitment

England
Northern Ireland
Scotland
United Kingdom
Wales

Study participating centre

Trial Manager

ICR-CTSU
Sir Richard Doll Building
Sutton, Surrey
SM2 5NG
United Kingdom

Sponsor information

The Royal Marsden NHS Foundation Trust / The Institute of Cancer Research (UK)
Charity

c/o Institute of Cancer Research
Clinical Trials and Statistics Unit
Section of Epidemiology
Brookes Lawley Building
Cotswold Road
Sutton, Surrey
SM2 5NG
United Kingdom

Website	http://www.icr.ac.uk/research/research_sections/clinical_trials/index.shtml
"ROR"	https://ror.org/0008wzh48

Funders

Funder type

Industry

Educational grants from:

No information available

AstraZeneca (UK)
Government organisation / For-profit companies (industry)

Alternative name(s): AstraZeneca PLC, Pearl Therapeutics
Location: United Kingdom

AstraZeneca (Global)
Government organisation / For-profit companies (industry)

Alternative name(s): AstraZeneca PLC, Pearl Therapeutics
Location: United Kingdom

Results and Publications

Intention to publish date	01/09/2013
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request, Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan	The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. sofea-icrctsu@icr.ac.uk

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/09/2013		Yes	No
Plain English results			27/07/2022	No	Yes

Editorial Notes

18/12/2023: The following changes were made:
1. Ethics approval information was updated.
2. The total final enrolment was changed from 723 to 698.
3. Northern Ireland, Scotland and Wales were added as Countries of recruitment.
4. The intention to publish date was added.
5. Study participating centre address was added.
15/05/2023: The participant-level data-sharing statement was added.
27/07/2022: Cancer Research UK plain English results summary link and total final enrolment added.