Fulvestrant With or Without Anastrozole or Exemestane Alone in Treating Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00253422
Recruitment Status : Unknown
Verified May 2011 by National Cancer Institute (NCI).
Recruitment status was:  Active, not recruiting
First Posted : November 15, 2005
Last Update Posted : May 17, 2011
Information provided by:
National Cancer Institute (NCI)

November 11, 2005
November 15, 2005
May 17, 2011
March 2004
May 2016   (Final data collection date for primary outcome measure)
Progression-free survival
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Complete list of historical versions of study NCT00253422 on Archive Site
  • Objective complete response (CR) and partial response (PR) rate
  • Duration of response
  • Clinical benefit (i.e., 6-month CR, PR, and stable disease) rate
  • Duration of clinical benefit
  • Time to treatment failure
  • Overall survival
  • Tolerability
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Fulvestrant With or Without Anastrozole or Exemestane Alone in Treating Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer
A Partially-Blind Phase III Randomized Trial of Fulvestrant (Faslodex™) With or Without Concomitant Anastrozole (Arimidex™) Compared With Exemestane in Postmenopausal Women With ER+ve Locally Advanced/Metastatic Breast Cancer Following Progression on Non-Steroidal Aromatase Inhibitors

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.



  • 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.


  • 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.

Phase 3
Allocation: Randomized
Masking: Double
Primary Purpose: Treatment
Breast Cancer
  • Drug: anastrozole
  • Drug: exemestane
  • Drug: fulvestrant
Not Provided
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.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Unknown status
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May 2016   (Final data collection date for primary outcome measure)


  • Histologically or cytologically confirmed adenocarcinoma of the breast

    • Locally advanced or metastatic disease
  • Metastatic disease must be measurable or evaluable

    • Patients with bone only metastases are eligible provided there is an evaluable site of bone metastasis that can be followed by x-ray, MRI, or CT scan
  • 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



  • 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


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

    • No thrombocytopenia
  • Hemoglobin ≥ 10 g/dL


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


  • Creatinine < 1.97 mg/dL


  • 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



  • 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


  • 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
Sexes Eligible for Study: Female
Child, Adult, Older Adult
Contact information is only displayed when the study is recruiting subjects
United Kingdom
Not Provided
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Institute of Cancer Research, United Kingdom
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Study Chair: Stephen R. D. Johnston, MD, PhD, FRCP Royal Marsden NHS Foundation Trust
National Cancer Institute (NCI)
May 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP