Clinical trial NCT00253422: Study of Faslodex +/- Concomitant Arimidex v Exemestane Following Progression on Non-steroidal Aromatase Inhibitors
Official title: A Partially Blind Phase III Randomised Trial of Faslodex +/- Concomitant Arimidex Compared With Exemestane in Post-menopausal Women With ER+ or PR+ Locally Advanced/Metastatic Breast Cancer Following Progression on Non-steroidal AIs
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: recurrent breast cancer
stage IV breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
Lead sponsor: Institute of Cancer Research, United Kingdom
Sponsor class: OTHER
Collaborators: name: Royal Marsden NHS Foundation Trust
First posted: 2005-11-15
Enrollment: 698
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression-free Survival
timeFrame: Assessed up to 190 months
Secondary outcomes:
measure: Objective Response Rate
timeFrame: From start of treatment, every 3 months to treatment discontinuation and/or up to 190 months
measure: Duration of Response
timeFrame: Assessed up to 190 months
measure: Clinical Benefit Rate
timeFrame: Assessed up to 190 months
measure: Duration of Clinical Benefit
timeFrame: Assessed up to 190 months
measure: Time to Treatment Failure
timeFrame: To discontinuation of protocol treatment for any reason, or progression of disease assessed up to 190 months
measure: Overall Survival
timeFrame: To death assessed up to 190 months.
measure: Tolerability of Treatment
timeFrame: From start of treatment to discontinuation of treatment/progression assessed up to 190 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Royal Marsden - London
state: England
city: Sutton
country: United Kingdom
facility: Institute Of Cancer Research
state: England
Study officials:
affiliation: Royal Marsden NHS Foundation Trust
name: Stephen RD Johnston, MD,PhD,FRCP
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.