Study of Zoladex Given Every 12 Weeks Versus Given Every Month in Advanced Breast Cancer (ABC) Pre-menopausal Women

Study Overview
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Brief Summary
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The primary objective is to evaluate whether Zoladex 10.8 mg (12-weekly) is non-inferior to Zoladex 3.6 mg (4-weekly) in pre-menopausal women with oestrogen receptor positive advanced breast cancer by assessment of progression-free survival at 24 weeks. Secondary Objectives are to compare the safety and tolerability profile of ZOLADEX 10.8 mg and ZOLADEX 3.6 mg by assessment of adverse events (AEs)and to assess goserelin PK in Japanese and Caucasian participants who have received ZOLADEX 10.8 mg by assessment of goserelin plasma concentration time profiles Recruitment into the study has been permanently stopped as of 24 December 2007 due to slow recruitment. 98 (vs the planned 260) patients were randomised into the study and will be followed as per protocol for 2 years

Official Title
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An Open-label, Randomised, Parallel Group, Multicentre Study to Compare ZOLADEX 10.8 mg Given Every 12 Weeks With ZOLADEX 3.6 mg Given Every 4 Weeks in Pre-menopausal Women With Oestrogen Receptor Positive Advanced Breast Cancer

Conditions
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Advanced Breast Cancer

Intervention / Treatment
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* Drug: Goserelin acetate
* Drug: Goserelin acetate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pre-menopausal women aged 18 years or over with histologically/cytologically-confirmed oestrogen receptor positive (ER +ve) breast cancer World Health Organization (WHO) performance status of 0, 1, or 2 Provided written informed consent Exclusion Criteria: Treatment with tamoxifen or other hormonal therapies as early breast cancer (EBC) adjuvant in the previous 24 weeks Received radiotherapy within the past 4 weeks History of systemic malignancy other than breast cancer within the previous 3 years Estimated survival less than 24 weeks

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ZOLADEX 10.8 mg<br>ZOLADEX (goserelin acetate) 10.8 mg intramuscular depot for injection every 12 weeks | Drug: Goserelin acetate<br>* 10.8 mg intramuscular depot injection given every 12 weeks<br>* Other names: Zoladex®;|
| Experimental: ZOLADEX 3.6 mg<br>ZOLADEX (goserelin acetate) 3.6 mg intramuscular depot for injection every 4 weeks | Drug: Goserelin acetate<br>* 3.6 mg intramuscular depot injection given every 4 weeks<br>* Other names: Zoladex®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Progression Free Survival (PFS) at Week 24 | The number of participants for whom neither objective disease progression or death (due to any cause) has been observed at Week 24 over the number of randomised participants x 100. | Objective tumour assessments carried out every 12 weeks (+/- 7 days) until Week 24, and then every 24 weeks (+/- 14 days) until Week 96 or objective progression is confirmed according to Response Evaluation Criteria in Solid Tumours (RECIST). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) at Week 24 | Number of participants who were objective responders at Week 24 over the number of participants evaluable for response x 100. An objective responder = a participants whose best unconfirmed response is either CR (Complete Response Disappearance of all target lesions) or PR (Partial Response At least a 30% decrease in target lesions) | Response Evaluation Criteria in Solid Tumours (RECIST) tumour assessments carried out every 12 weeks from randomisation until Week 24 in those patients with measurable disease at baseline. | 
| Oestradiol (E2) Serum Concentrations at Week 24 | A comparison of mean E2 serum concentrations at timepoint(s) post Day 1 performed using analysis of covariance (ANCOVA), with treatment group, baseline E2 serum concentrations and country as covariates. Data analysed on the log scale; log scale mean and pooled log scale standard deviation from Analysis of Covariance (ANCOVA) presented. | Blood samples for measurement of E2 concentrations collected from all patients at scheduled visits of screening, Day 1 and Weeks 12 and 24 (+/- 7 days). Week 24 data is presented | 
| Maximum Plasma Concentration, Cmax (ng/mL) | Maximum plasma concentration, Cmax (ng/mL), derived from analysis of pharmacokinetic (PK) outcomes samples provided only by participants in the PK subgroup set (all of whom received ZOLADEX 10.8 mg) | Blood samples taken at Days 1, 2 and 3, Weeks 4, 12 and 24. Derived from the individual goserelin plasma concentration-time profiles following the first dose of study drug for patients in the pharmacokinetic (PK) subgroup | 
| Time to Maximum Plasma Concentration, Tmax (Hours) | Time to maximum plasma concentration, Tmax (hours), derived from analysis of pharmacokinetic (PK) outcomes samples provided only by participants in the PK subgroup set (all of whom received ZOLADEX 10.8 mg) | Blood samples taken at Days 1, 2 and 3, Weeks 4, 12 and 24. Derived from the individual goserelin plasma concentration-time profiles following the first dose of study drug for patients in the pharmacokinetic (PK) subgroup | 
| Area Under the Plasma Concentration Curve (0-12 Weeks) | Area under the plasma concentration curve (0-12 weeks) derived from analysis of pharmacokinetic (PK) outcomes samples provided only by participants in the PK subgroup set (all of whom received ZOLADEX 10.8 mg) | Blood samples taken at Days 1, 2 and 3, Weeks 4, 12 and 24. Derived from the individual goserelin plasma concentration-time profiles following the first dose of study drug for patients in the pharmacokinetic (PK) subgroup | 

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