A Global Study to Compare the Effects of Fulvestrant and Arimidex in a Subset of Patients With Breast Cancer.

Study Overview
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Brief Summary
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The purpose of the study is to compare how treatment with Fulvestrant (FASLODEX) or Anastrozole (ARIMIDEX) effects disease progression for women with locally advanced or metastatic breast cancer who have not had prior hormonal treatment.

Detailed Description
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A Randomised, Double-blind, Parallel-group, Multicentre, Phase III Study to Compare the Efficacy and Tolerability of Fulvestrant (FASLODEX) 500 mg with Anastrozole (ARIMIDEX) 1 mg as Hormonal Treatment for Postmenopausal Women with Hormone Receptor-Positive Locally Advanced or Metastatic Breast Cancer Who Have Not Previously Been Treated With Any Hormonal Therapy.

Official Title
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A Randomised, Double-blind, Parallel-group, Multicentre, Phase III Study to Compare the Efficacy and Tolerability of Fulvestrant (FASLODEX) 500 mg With Anastrozole (ARIMIDEX) 1 mg as Hormonal Treatment for Postmenopausal Women With Hormone Receptor-Positive Locally Advanced or Metastatic Breast Cancer Who Have Not Previously Been Treated With Any Hormonal Therapy.

Conditions
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Hormone Receptor Positive Breast Cancer

Intervention / Treatment
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* Drug: faslodex 500mg
* Drug: arimidex 1mg
* Drug: faslodex dummy
* Drug: arimidex dummy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological confirmation of breast cancer in post menopausal women (age >=60). Positive hormone receptor status (ER +ve and/or PgR +ve) of primary or metastatic tumour tissue based on local laboratory assessment. EITHER locally advanced disease (1 line of chemotherapy allowed only if remain unsuitable for therapy of curative intent) OR Metastatic disease. (1 line of chemotherapy for breast cancer allowed only if subsequent evidence of further progressive disease) At least 1 lesion (measurable and/or non-measurable) that can be accurately assessed at baseline and is suitable for repeated assessment. Postmenopausal women, fulfilling 1 of: Prior bilateral oophorectomy Age >60 years Age < 60 years and amenorrheic for 12+months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression and FSH and oestradiol in the postmenopausal range Exclusion Criteria: Presence of life-threatening metastatic disease Any of: Extensive hepatic involvement involving brain or meninges symptomatic pulmonary lymph spread Discrete lung metastases are acceptable if respiratory function is not significantly compromised Prior systemic therapy for breast cancer other than one line of cytotoxic chemotherapy (the last dose of chemotherapy must have been received more than 28 days prior to randomisation) Radiation therapy if not completed within 28 days prior to randomisation (with the exception of radiotherapy given for control of bone pain, started prior to randomisation). Prior hormonal treatment for breast cancer. Current or prior malignancy within previous 3 years (other than breast cancer or adequately treated basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: faslodex+placebo<br>Blinded: Fulvestrant 500mg intramuscular injection (2x250mg) plus dummy Anastrozole tablets | Drug: faslodex 500mg<br>* 2 x intramuscular injections at day 1, 14, 28 and every 28 days thereafter<br>Drug: arimidex dummy<br>* oral tablet 1 daily<br>|
| Active Comparator: arimidex +placebo<br>Blinded: Anastrozole 1mg tablets plus dummy Fulvestrant intramuscular injection (2x0mg) | Drug: arimidex 1mg<br>* oral tablet 1 daily<br>Drug: faslodex dummy<br>* 2 x intramuscular injections at day 1, 14, 28 and every 28 days thereafter<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Progression Free Survival (PFS) in Patients Treated With Fulvestrant With Those Treated With Anastrozole | PFS was defined as the time from randomisation until objective disease progression according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1), surgery or radiotherapy to manage worsening of disease or death by any cause (in the absence of progression). Outcome measure is reported as median time from randomisation to PFS, calculated using the Kaplan-Meier technique. | Baseline RECIST 1.1 assessments and then every 12 weeks until the earliest of disease progression evident, patient dies or has surgery/radiotherapy for their disease (up to approximately 38 months for the primary analysis data cut-off). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Overall Survival (OS) in Patients Treated With Fulvestrant With Those Treated With Anastrozole; Percentage of Patients With Events | OS was defined as the time from randomisation until death by any cause. Two timepoints were planned for OS analysis: an interim OS analysis at the time of the data cut-off for PFS analysis and a final OS analysis when 75% of the deaths have occurred. The current OS data correspond to that of the interim analysis only and the outcome measure is reported as percentage of patients with events. | Baseline up to data cut-off for PFS analysis (up to approximately 38 months). Following disease progression, patients were to be contacted at 12 weekly intervals to to determine survival status. | 
| Objective Response Rate (ORR) for Fulvestrant Treatment Versus Anastrozole Treatment | ORR was defined as the percentage patients with an objective response (i.e. those recording a partial response [PR] or complete response [CR]) at some point during the study, prior to disease progression. ORR was assessed in patients with measurable disease at baseline only. The determination of measurable disease at baseline was done using baseline RECIST data. | Baseline RECIST 1.1 assessments and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months for the primary analysis data cut-off). | 
| Duration of Response (DoR) for Fulvestrant Treatment Versus Anastrozole Treatment | DoR was defined only for patients who had an objective response, as the time in days from date of first documentation of response (CR/PR) until date of disease progression. | Baseline RECIST 1.1 assessments and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months for the primary analysis data cut-off).. | 
| Expected Duration of Response (EDoR) for Fulvestrant Treatment Versus Anastrozole Treatment | EDoR was estimated using the formula EDoR = p Efp(x), where x = DoR, p = proportion of responders, and Efp(x) = mean duration of response for responders. The estimation was completed by using the maximum likelihood estimates of p and Efp(x), as described by Ellis (Ellis S et al. Analysis of duration of response in oncology trials, Contemp Clin Trials 2008; 29:456-65). | Baseline RECIST 1.1 assessments and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months for the primary analysis data cut-off). | 
| Clinical Benefit Rate (CBR) for Fulvestrant Treatment Versus Anastrozole Treatment | CBR was defined as the percentage of patients who had a clinical benefit (i.e. best objective response of CR, PR or stable disease), that was maintained for at least 24 weeks, prior to any evidence of progression. Note that a minimum duration of 22 weeks for CBR was applicable in the analysis (rather than 24 weeks) to allow for the protocolled window of +/-2 weeks. | Baseline RECIST 1.1 assessments and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months for the primary analysis data cut-off). | 
| Duration of Clinical Benefit (DoCB) for Fulvestrant Treatment Versus Anastrozole Treatment | DoCB was defined only for patients who had clinical benefit, as the time in days from date of randomisation until the date of disease progression. | Baseline RECIST 1.1 assessments and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months for the primary analysis data cut-off). | 
| Expected Duration of Clinical Benefit (EDoCB) for Fulvestrant Treatment Versus Anastrozole Treatment | EDoCB was estimated using the formula EDoCB = p Efp(x), where x = EDoCB, p = proportion of responders, and Efp(x) = mean duration of response for responders. The estimation was completed by using the maximum likelihood estimates of p and Efp(x), as described by Ellis (Ellis S et al. Analysis of duration of response in oncology trials, Contemp Clin Trials 2008; 29:456-65). | Baseline RECIST 1.1 assessments and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months for the primary analysis data cut-off). | 
| Comparison of the Effect of Fulvestrant Treatment Versus Anastrozole Treatment on Time to Deterioration of Health Related Quality of Life (HRQoL) | The Functional Assessment of Cancer Therapy - Breast (FACT-B) questionnaire was the instrument selected to assess HRQoL and comprises the following subscales: physical well-being (PWB), functional well-being (FWB), social well-being, emotional well-being, and breast cancer subscale (BCS). The main outcome measure from the FACT-B questionnaire was the Trial Outcome Index (TOI), which was a summary of the following subscales: PWB, FWB, and BCS. Outcome measure is reported as median time to deterioration, defined as the interval from the date of randomisation to the first assessment of worsened without an improvement in the next 12 weeks in FACT-B TOI, or the date of death (by any cause in the absence of symptom deterioration). Time to deterioration as measured by FACT-B total score was derived similarly and is also reported. | Quality of life questionnaires completed at baseline and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months for the primary analysis data cut-off). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hormone receptor positive breast cancer, endocrine, no hormone therapy, hormone, breast, cancer, neoplasm, metastatic, tumour