Study of Faslodex +/- Concomitant Arimidex v Exemestane Following Progression on Non-steroidal Aromatase Inhibitors

NCT ID: NCT00253422

Last Updated: 2025-06-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 698 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-03-26
• Study Completion Date: 2022-11-28

Brief Summary

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using fulvestrant, anastrozole, or exemestane may fight breast cancer by blocking the use of estrogen by the tumor cells or by lowering the amount of estrogen the body makes. It is not yet known whether giving fulvestrant together with anastrozole is more effective than giving fulvestrant together with a placebo or exemestane alone in treating breast cancer.

PURPOSE: This randomized 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.

Detailed Description

OBJECTIVES:

Primary

• Compare progression-free survival of postmenopausal women with estrogen receptor- and/or progesterone receptor-positive, locally advanced or metastatic breast cancer that relapsed or progressed during prior treatment with nonsteroidal aromatase inhibitors treated with fulvestrant with vs without anastrozole vs exemestane alone.

Secondary

• Compare the objective complete response (CR) and partial response (PR) rate and duration of response in patients treated with these regimens.
• Compare the clinical benefit (i.e., 6-month CR, PR, and stable disease) rate and duration of clinical benefit in patients treated with these regimens.
• Compare time to treatment failure in patients treated with these regimens.
• Compare the overall survival of patients treated with these regimens.
• Compare the tolerability of these regimens in these patients.

OUTLINE: This is a randomized, partially double-blind and placebo-controlled, multicenter study. Patients are stratified according to the setting in which prior nonsteroidal aromatase-inhibitor therapy was given (adjuvant therapy vs first-line therapy) and participating center. Patients are randomized to 1 of 3 treatment arms.

• Arm I (fulvestrant and anastrozole): Patients receive fulvestrant intramuscularly (IM) on days 1, 15, and 29 and then once monthly. Patients receive oral anastrozole once daily.
• Arm II (fulvestrant and placebo): Patients receive fulvestrant as in arm I and oral placebo once daily.
• Arm III (exemestane alone): Patients receive oral exemestane once daily. In all arms, treatment repeats every month in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for survival.

PROJECTED ACCRUAL: A total of 750 patients (250 per treatment arm) will be accrued for this study.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Faslodex + placebo

Arimidex/placebo comparator is blinded Faslodex (fulvestrant) IM on day 1,15,29 and monthly thereafter Placebo orally once a day

Group Type: ACTIVE_COMPARATOR

Anastrozole

Intervention Type: DRUG

This may be Anastrazole OR a placebo

Fulvestrant

Intervention Type: DRUG

Faslodex + Arimidex

Arimidex/placebo comparator is blinded Faslodex (fulvestrant) IM on day 1,15,29 and monthly thereafter Arimidex (anastrozole) orally once a day

Group Type: ACTIVE_COMPARATOR

Anastrozole

Intervention Type: DRUG

This may be Anastrazole OR a placebo

Fulvestrant

Intervention Type: DRUG

Exemestane

exemestane orally once a day

Group Type: ACTIVE_COMPARATOR

Exemestane

Intervention Type: DRUG

Interventions

Anastrozole

This may be Anastrazole OR a placebo

Intervention Type: DRUG

Exemestane

Intervention Type: DRUG

Fulvestrant

Intervention Type: DRUG

Other Intervention Names

Arimidex (or placebo); Faslodex

Eligibility Criteria

Inclusion Criteria

• Relapsed or progressed during prior treatment with single-agent nonsteroidal aromatase inhibitor (NSAI)*, meeting either of the following criteria:

• NSAI given as adjuvant therapy that lasted ≥ 12 months
• Achieved an objective complete response, partial response, or stable disease that lasted ≥ 6 months after prior first-line therapy with NSAI for locally advanced or metastatic disease

• Chemotherapy as part of the first-line therapy given before initiation of NSAI allowed NOTE: *Patients are required to continue to take NSAI until beginning of study treatment.
• No rapidly progressive visceral disease (i.e., lymphangitis carcinomatosa or diffuse hepatic involvement)
• Hormone receptor status:

• Estrogen receptor (ER) and/or progesterone receptor positive tumor
• No ER-unknown disease

PATIENT CHARACTERISTICS:

Sex

• Female

Menopausal status

• Postmenopausal, as defined by 1 of the following criteria:

• Age 60 and over
• Age 45 to 59 AND ≥ 12 months since last menstrual period with no prior hysterectomy
• Any age with prior bilateral oophorectomy

Performance status

• WHO 0-2

Life expectancy

• More than 3 months

Hematopoietic

• Neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

• No thrombocytopenia
• Hemoglobin ≥ 10 g/dL

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 5 times ULN (unless due to bone metastases)
• No liver disease

Renal

• Creatinine < 1.97 mg/dL

Other

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Chemotherapy

• See Disease Characteristics
• Prior neoadjuvant or adjuvant chemotherapy allowed

Endocrine therapy

• See Disease Characteristics
• Prior tamoxifen as neoadjuvant or adjuvant therapy allowed
• No systemic corticosteroids that lasted > 15 days within the past 4 weeks

Other

• More than 4 weeks since prior investigational drugs
• Concurrent bisphosphonates for bone metastases allowed provided bisphosphonate therapy has been established for ≥ 6 months

• Concurrent initiation of bisphosphonate allowed provided patient has soft tissue or visceral metastases as the measurable or evaluable target lesion
• No concurrent anticoagulant therapy
• No concurrent unlicensed noncancer investigational agents

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Royal Marsden NHS Foundation Trust

OTHER

Sponsor Role: collaborator

Institute of Cancer Research, United Kingdom

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephen RD Johnston, MD,PhD,FRCP

Role: STUDY_CHAIR

Royal Marsden NHS Foundation Trust

Locations

Royal Marsden - London

London, England, United Kingdom

Institute Of Cancer Research

Sutton, England, United Kingdom

Countries

United Kingdom

References

Johnston SR, Kilburn LS, Ellis P, Dodwell D, Cameron D, Hayward L, Im YH, Braybrooke JP, Brunt AM, Cheung KL, Jyothirmayi R, Robinson A, Wardley AM, Wheatley D, Howell A, Coombes G, Sergenson N, Sin HJ, Folkerd E, Dowsett M, Bliss JM; SoFEA investigators. Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial. Lancet Oncol. 2013 Sep;14(10):989-98. doi: 10.1016/S1470-2045(13)70322-X. Epub 2013 Jul 29.

Reference Type: RESULT

PMID: 23902874 (View on PubMed)

Fribbens C, O'Leary B, Kilburn L, Hrebien S, Garcia-Murillas I, Beaney M, Cristofanilli M, Andre F, Loi S, Loibl S, Jiang J, Bartlett CH, Koehler M, Dowsett M, Bliss JM, Johnston SR, Turner NC. Plasma ESR1 Mutations and the Treatment of Estrogen Receptor-Positive Advanced Breast Cancer. J Clin Oncol. 2016 Sep 1;34(25):2961-8. doi: 10.1200/JCO.2016.67.3061. Epub 2016 Jun 6.

Reference Type: DERIVED

PMID: 27269946 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.icr.ac.uk/research-and-discoveries/centres-and-strategic-collaborations/clinical-trials-and-statistics-unit-icr-ctsu/detail/sofea

Clinical trial summary from ICR website

Other Identifiers

ICR-CTSU-SOFEA

Identifier Type: OTHER

Identifier Source: secondary_id

ISRCTN44195747

Identifier Type: OTHER

Identifier Source: secondary_id

MREC-03677

Identifier Type: OTHER

Identifier Source: secondary_id

2004-000093-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CDR0000448616

Identifier Type: -

Identifier Source: org_study_id