Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active Any age Other ICR-CTSU-SOFEA EU-20531, SSA-04Q200635, ISRCTN44195747, MREC-03677, EUDRACT-2004-000093-30, NCT00253422

Objectives

Primary

1. 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

1. Compare the objective complete response (CR) and partial response (PR) rate and duration of response in patients treated with these regimens.
2. 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.
3. Compare time to treatment failure in patients treated with these regimens.
4. Compare the overall survival of patients treated with these regimens.
5. Compare the tolerability of these regimens in these patients.

Entry Criteria

Disease Characteristics:

• 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

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

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/mm³
• Platelet count ≥ 100,000/mm³
  • 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

Expected Enrollment

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

Outcomes

Progression-free survival

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

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.

Trial Contact Information

Trial Lead Organizations

Institute of Cancer Research - Sutton

Stephen Johnston, MD, PhD, FRCP, Protocol chair		Ph: 44-20-7808-2748

United Kingdom
England
	London
	Royal Marsden - London
		Stephen Johnston, MD, PhD, FRCP	Ph:  44-20-7808-2748
	Sutton
	Institute of Cancer Research - Sutton
		Gill Coombes	Ph:  44-20-8722-4039

Registry Information
Official Title		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
Trial Start Date		2004-03-01
Registered in ClinicalTrials.gov		NCT00253422
Date Submitted to PDQ		2005-09-01
Information Last Verified		2008-04-20