Comparison of Fulvestrant (FASLODEX™) 250 mg and 500 mg in Postmenopausal Women With Oestrogen Receptor Positive Advanced Breast Cancer Progressing or Relapsing After Previous Endocrine Therapy.

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the efficacy of a new dose of 500 mg Fulvestrant with the standard dose of 250 mg in postmenopausal women with oestrogen receptor positive advanced breast cancer who have failed on a previous endocrine treatment.

Official Title
-----------------
A Randomised, Double-Blind, Parallel-group, Multicentre, Phase III Study Comparing the Efficacy and Tolerability of Fulvestrant (FASLODEX™) 500 mg With Fulvestrant (FASLODEX™) 250 mg in Postmenopausal Women With Oestrogen Receptor Positive Advanced Breast Cancer Progressing or Relapsing After Previous Endocrine Therapy

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: Fulvestrant


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Breast Cancer has continued to grow after having received treatment with an anti-estrogen hormonal treatment such as tamoxifen or an aromatase inhibitor Requiring hormonal treatment Postmenopausal women defined as a woman who has stopped having menstrual periods Evidence of positive estrogen receptor hormone sensitivity Written informed consent to participate in the trial Exclusion Criteria: Treatment with an investigational or non-approved drug within one month An existing serious disease, illness, or condition that will prevent participation or compliance with study procedures A history of allergies to any active or inactive ingredients of Faslodex (i.e. castor oil) Treatment with more than one regimen of chemotherapy for advanced breast cancer Treatment with more than one regimen of hormonal treatment for advanced breast cancer

Ages Eligible for Study
-----------------
Minimum Age: 45 Years
Maximum Age: 130 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Fulvestrant 500 mg | Drug: Fulvestrant<br>* intramuscular injection<br>* Other names: ZD9238;|
| Experimental: 2<br>Fulvestrant 250 mg | Drug: Fulvestrant<br>* intramuscular injection<br>* Other names: ZD9238;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression (TTP) | Median time (in months) from randomisation until objective disease progression or death (in the absence of objective progression). | RECIST(Response Evaluation Criteria in Solid Tumors ) tumour assessments carried out every 12 weeks (+/- 2 weeks) from randomisation for study duration (48 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Using the RECIST scan data, an objective response (OR) is defined as a patient having a best overall response of either complete response (CR) or partial response (PR) which is subsequently confirmed as per RECIST. ORR is defined as the percentage of patients with OR. | RECIST tumour assessments carried out every 12 weeks (+/- 2 weeks) from randomisation for study duration (48 months) | 
| Clinical Benefit Rate (CBR) | A Clinical Benefit (CB) responder is defined as a patient having a best overall response of CR, PR or SD (stable disease) >=24 weeks. The Clinical Benefit Rate is the percentage of patients with CB. | Clinical Benefit from the sequence of RECIST scan data for study duration (48 months) . RECIST (Response Evaluation Criteria in Solid Tumours) scans were performed every 12 weeks (+/- 2 weeks) from randomisation for study duration (48 months) | 
| Duration of Response (DoR) | Time from randomisation until objective progression or death (in the absence of objective progression), measured only in those patients who achieve a confirmed complete response (CR) or confirmed partial response (PR) | RECIST tumour assessments carried out every 12 weeks (+/- 2 weeks) from randomisation for study duration (48 months) | 
| Duration of Clinical Benefit (DoCB) | Time from randomisation until objective progression or death (in the absence of objective progression), measured only in those patients who achieve a confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) >=24 weeks | RECIST tumour assessments carried out every 12 weeks (+/- 2 weeks) from randomisation for study duration (48 months) | 
| Overall Survival (OS) | Median time (in months) from randomisation until death (from any cause) (analysis at 50% deaths ) | Overall Survival is equivalent to time to death. For this endpoint, all deaths occurring for study duration (48 months) | 
| Change From Randomisation in Trial Outcome Index (TOI) Over the Course of the Study | Mean (and standard deviation) change from randomisation until treatment discontinuation in TOI (defined as the first visit response of 'worsened' which is a decrease in TOI from baseline of 5 points or more) using the Kaplan-Meier method. If a subject has not shown a reduction of 5 points or more at the time of analysis then the observation will be right censored using the last QOL assessment date. Trial Outcome Index (TOI) is derived from the FACT-B questionnaire (Cella et al, 1993) by adding together the scores from the following 3 subscales; Physical well-being (PWB), Functional well-being (FWB) and Breast cancer subscale (BCS). The TOI score range is 0-92 with the higher scores representing the more favourable outcomes. Data were collected from a subgroup of patients. | TOI questionnaires were completed every 4 weeks from randomisation until week 24 and then again at treatment discontinuation, for study duration (48 months) | 
| Overall Survival (OS) - Follow-up | Overall Survival is equivalent to time to death. For this endpoint, all deaths occurring during the study as a whole until the data cut-off for the survival extension (31st October 2011) are presented (analysis at 75% deaths) | Median time (in months) from randomisation until death (from any cause),up to 80 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Advanced Breast Cancer, Metastatic Breast Cancer