A Clinical Trial to Compare Efficacy and Tolerability of Fulvestrant 250mg, 250mg Plus 250mg Loading Regimen and 500mg

Study Overview
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Brief Summary
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This study will assess the relationship between fulvestrant dose and efficacy in postmenopausal women with oestrogen receptor positive advanced breast cancer.

Official Title
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Phase II Study to Evaluate the Efficacy and Tolerability of Fulvestrant 250mg, 250mg Plus 250mg Loading Regimen and 500mg in Postmenopausal Women With ER +ve Advanced Breast Cancer Progressing or Relapsing After Previous Endocrine Therapy

Conditions
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Advanced Breast Cancer, Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Fulvestrant


Participation Criteria
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Eligibility Criteria
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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 (woman who has stopped having menstrual periods) Exclusion Criteria: Treatment with more than one previous regimen of systemic anticancer therapy other than endocrine therapy for advanced BC. Treatment with more than one previous regimen of endocrine therapy for advanced BC. An existing condition that prevents compliance.

Ages Eligible for Study
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Minimum Age: 45 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: 1<br>Fulvestrant 250 mg (intramuscular injection 250 mg) | Drug: Fulvestrant<br>* intramuscular injection 250 mg & 500 mg<br>* Other names: ZD9238;|
| Experimental: 2<br>Fulvestrant 250 mg (+ 250 mg loading regimen) | Drug: Fulvestrant<br>* intramuscular injection 250 mg & 500 mg<br>* Other names: ZD9238;|
| Experimental: 3<br>Fulvestrant 500 mg (intramuscular injection 500 mg) | Drug: Fulvestrant<br>* intramuscular injection 250 mg & 500 mg<br>* Other names: ZD9238;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response (ORR) | Objective response rate was defined as percentage of patients with either complete response (CR - disappearance of all target lesions) or partial response (PR - at least 30% decrease in the sum of diameters of target lesions). All patients were to be followed up every 12 weeks for progression, defined by response evaluation criteria in solid tumors (RECIST v1.1). | The planned data cut-off for this study was when all patients, except withdrawals, had been followed up for at least 24 weeks. Patients received treatment up to approximately 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression (TTP) | Time from randomisation until objective disease progression or death (in the absence of objective progression) using the Kaplan-Meier method. RECIST tumor assessments were carried out every 12 weeks until progression. | The planned data cut-off for this study was when all patients, except withdrawals, had been followed up for at least 24 weeks. Patients received treatment up to approximately 2 years. | 
| Duration of Response (DoR) | DoR was defined as the time from date of first documentation of the response (CR or PR) until the date of disease progression or death from any cause. | The planned data cut-off for this study was when all patients, except withdrawals, had been followed up for at least 24 weeks. Patients received treatment up to approximately 2 years. | 
| Clinical Benefit Rate (CBR) | CBR was defined as the proportion of all randomised patients who had clinical benefit (response of CR, PR or SD>=24 weeks. | The planned data cut-off for this study was when all patients, except withdrawals, had been followed up for at least 24 weeks. Patients received treatment up to approximately 2 years. | 
| Pharmacokinetic Parameter: Mean Population Clearance, a Measure of the Efficiency With Which Fulvestrant is Eliminated From the Body | A 2-compartment model with a 1st order absorption and 1st order elimination process was fitted to the fulvestrant concentration-time data. Relative standard error is reported for the mean. | Baseline to 12 weeks | 
| Pharmacokinetic Parameter: Mean Volume of Distribution at Steady State, a Measure of the Apparent Volume in the Body Into Which Fulvestrant Distributes | A 2-compartment model with a 1st order absorption and 1st order elimination process was fitted to the fulvestrant concentration-time data. Relative standard error is reported for the mean. The mean estimate of volume of distribution at steady state was reported as the sum of V1/F and V2/F in the clinical study report. | Baseline to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oncology, cancer, breast cancer