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

• ClinicalTrials.gov Identifier: NCT00253422
• Recruitment Status: Unknown
• First Posted: November 15, 2005
• Last Update Posted: May 17, 2011
• Sponsor: Institute of Cancer Research, United Kingdom
• Information provided by: National Cancer Institute (NCI)

Tracking Information

• First Submitted Date: November 11, 2005
• First Posted Date: November 15, 2005
• Last Update Posted Date: May 17, 2011
• Study Start Date: March 2004
• Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 16, 2007): Progression-free survival
• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: May 16, 2007)

• 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

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Masking: Double; Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

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

• Study Arms: Not Provided

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: November 8, 2006): 750
• Original Enrollment: Not Provided
• Study Completion Date: Not Provided
• Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)

Eligibility 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

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT00253422
• Other Study ID Numbers: CDR0000448616; ICR-CTSU-SOFEA; EU-20531; SSA-04Q200635; ISRCTN44195747; MREC-03677; EUDRACT-2004-000093-30
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Not Provided
• Original Responsible Party: Same as current
• Current Study Sponsor: Institute of Cancer Research, United Kingdom
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Stephen R. D. Johnston, MD, PhD, FRCP; Royal Marsden NHS Foundation Trust

• PRS Account: National Cancer Institute (NCI)
• Verification Date: May 2011