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”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control

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.

Intervention(s) in this Clinical Trial

• Drug: anastrozole
• Drug: exemestane
• Drug: fulvestrant

Primary Measures

• Progression-free survival
  • Safety Issue?: No

Secondary Measures

• Objective complete response (CR) and partial response (PR) rate
  • Safety Issue?: No
• Duration of response
  • Safety Issue?: No
• Clinical benefit (i.e., 6-month CR, PR, and stable disease) rate
  • Safety Issue?: No
• Duration of clinical benefit
  • Safety Issue?: No
• Time to treatment failure
  • Safety Issue?: No
• Overall survival
  • Safety Issue?: No
• Tolerability
  • Safety Issue?: Yes

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

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

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Institute of Cancer Research, United Kingdom

Overall Clinical Trial Officials and Contacts

Stephen R. D. Johnston, MD, PhD, FRCP Study Chair Royal Marsden - London  

Information obtained from ClinicalTrials.gov on December 03, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00253422

Study ID Number: CDR0000448616

ClinicalTrials.gov Identifier: NCT00253422

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database