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

This study is ongoing, but not recruiting participants.
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
First received: November 11, 2005
Last updated: May 14, 2011
Last verified: May 2011

November 11, 2005
May 14, 2011
March 2004
May 2016   (final data collection date for primary outcome measure)
Progression-free survival [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00253422 on ClinicalTrials.gov Archive Site
  • Objective complete response (CR) and partial response (PR) rate [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Clinical benefit (i.e., 6-month CR, PR, and stable disease) rate [ Designated as safety issue: No ]
  • Duration of clinical benefit [ Designated as safety issue: No ]
  • Time to treatment failure [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Tolerability [ Designated as safety issue: Yes ]
Not Provided
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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-Blind
Primary Purpose: Treatment
Breast Cancer
  • Drug: anastrozole
  • Drug: exemestane
  • Drug: fulvestrant
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Active, not recruiting
Not Provided
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
Not Provided
Contact information is only displayed when the study is recruiting subjects
United Kingdom
CDR0000448616, ICR-CTSU-SOFEA, EU-20531, SSA-04Q200635, ISRCTN44195747, MREC-03677, EUDRACT-2004-000093-30
Not Provided
Not Provided
Institute of Cancer Research, United Kingdom
Not Provided
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