Arimidex/Tamoxifen Neo Adjuvant Study in Premenopausal Patients With Breast Cancer Under Anti Hormonal Treatment

Study Overview
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Brief Summary
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The purpose of this multi-centre, randomised, double-blind, parallel-group study is to compare efficacy and safety between anastrozole and tamoxifen in pre- and post-operative administration under goserelin acetate treatment for premenopausal breast cancer patients

Official Title
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Multi-centre, Randomised, Double-blind, Parallel-group Study to Compare Efficacy and Safety Between Anastrozole (ZD1033) and Tamoxifen in Pre- and Post-operative Administration Under Goserelin Acetate Treatment for Premenopausal Breast Cancer Patients

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Tamoxifen
* Drug: Anastrazole (Arimidex)
* Drug: Goserelin acetate (Zoladex)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Premenopausal, estrogen receptor positive women, aged 20 years and over, with operable and measurable breast cancer who have provided written informed consent Exclusion Criteria: Medical history of chemotherapy or endocrine therapy for breast cancer, or with treatment history of radiotherapy. Unwillingness to stop taking any drug known to affect sex hormone status (including hormone replacement therapy (HRT).

Ages Eligible for Study
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Minimum Age: 20 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Tamoxifen | Drug: Tamoxifen<br>* 20 mg once daily oral dose<br>* Other names: NOLVADEX;Drug: Goserelin acetate (Zoladex)<br>* 3.6mg/month depot injection<br>* Other names: ZOLADEX;|
| Experimental: 2<br>Anastrazole (Arimidex) | Drug: Anastrazole (Arimidex)<br>* 1 mg once daily oral dose<br>* Other names: ZD1033;Drug: Goserelin acetate (Zoladex)<br>* 3.6mg/month depot injection<br>* Other names: ZOLADEX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response Rate (BORR) (Calliper) | The BORR were defined as the percentage of patients with confirmed CR or PR in the ITT population during 24 weeks pre-operative treatment period (based on the data from calliper measurement). CR (or PR) criteria are met at 2 or more time in points every 4 weeks. Per RECIST Criteria (V1.0) and assessed by Calliper: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | 24 weeks | 
| Best Overall Response Rate (BORR) (US) | The BORR were defined as the percentage of patients with confirmed CR or PR in the ITT population during 24 weeks pre-operative treatment period (based on the data from ultra sound (US) measurement). CR (or PR) criteria are met at 2 or more time in points every 4 weeks. Per RECIST Criteria (V1.0) and assessed by US: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | 24 weeks | 
| Best Overall Response Rate (BORR) (MRI/CT) | The BORR were defined as the percentage of patients with confirmed CR or PR in the ITT population during 24 weeks pre-operative treatment period(based on the data from magnetic resonance imaging (MRI) or computed tomography (CT) measurement). CR (or PR) criteria are met at either 12 weeks or 24 weeks. Per RECIST Criteria (V1.0) and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Mineral Density (BMD) Lumbar Spine | Change from baseline in Bone Mineral Density value (percentage), in all subjects who used DXA(Dual-energy X-ray absorptiometry) method throughout the study, at 24 weeks measured at lumbar spine. | Assessed at baseline and after 24 weeks of treatment | 
| Bone Mineral Density (BMD) Cervical Thighbone | Change from baseline in Bone Mineral Density value (percentage), in all subjects who used DXA(Dual-energy X-ray absorptiometry) method throughout the study, at 24 weeks measured at cervical thighbone. | Assessed at baseline and after 24 weeks of treatment | 
| Bone Turnover Marker (BAP) EIA Method | Change from baseline in serum Bone-Alkaline Phosphatase (BAP) at 24 weeks measured by EIA method | Assessed at baseline and after 24 weeks of treatment | 
| Bone Turnover Marker (BAP) CLEIA Method | Change from baseline in serum Bone-Alkaline Phosphatase (BAP) at 24 weeks measured by CLEIA method | Assessed at baseline and after 24 weeks of treatment | 
| Bone Turnover Marker (NTX) | Change from baseline in serum crosslinked N-Telopeptide of type I collagen (NTX) at 24 weeks | Assessed at baseline and after 24 weeks of treatment | 
| Serum Oestrone (E1) Concentrations | Ratio of serum Oestrone (E1) concentration (pg/mL) in the ITT population from baseline at 24 weeks. | Assessed at baseline and after 24 weeks of treatment | 
| Serum Oestradiol (E2) Concentrations | Ratio of serum Oestradiol (E2) concentration (pg/mL) in the ITT population from baseline at 24 weeks. | Assessed at baseline and after 24 weeks of treatment | 
| Oestrogen Receptor (ER) Status | ER status in the ITT population is categorized as Positive or Negative | Assessed at baseline and after 24 weeks of treatment | 
| Progesterone Receptor (PgR) Status | PgR status in the ITT population is categorized as Positive or Negative. | Assessed at baseline and after 24 weeks of treatment | 
| Human Epidermal Growth Factor Receptor 2 (HER2) Status | HER2 status in the ITT population is categorized as Positive or Negative | Assessed at baseline and after 24 weeks of treatment | 
| Histopathological Response Rate (HRR) | Number of patients in the ITT population defined as histopathological responders over the total number of patients x 100. An histopathological responder = a patient classified as Grade 1b, 2 or 3 for the histopathological response (Grade 0 = no response, 1a = mild response, 1b = moderate response, 2 = marked response or 3 = complete response) | Assessed at baseline and after 24 weeks of treatment | 
| Functional Assessment of Cancer Therapy-Breast (FACT-B) | Change from baseline in Functional Assessment of Cancer Therapy-Breast (FACT-B)in the ITT population at 24 weeks. Trial Outcome Index (TOI) = the sum of the Physical Well-Being (PWB), Functional Well-Being (FWB), and Breast Cancer Scale (BCS) subscales of FACT-B. FACT-B includes 36 questions; 7 in PWB (Physical Well-Being); 7 inSWB (Social / Family Well-Being); 6 in EWB (Emotional Well-Being); 7 in FWB (Functional Well-Being); 9 in BCS (Breast Cancer Subscale). Total score of subscores or TOI is calculated from each score of question. Higher score means better and lower score means worthier. Score range; 0-28 in PWB; 0-28 in SWB; 0-24 in EWB; 0-28 in FWB; 0-36 in BCS; 0-92 in TOI. | Assessed at baseline and after 24 weeks of treatment | 
| Endocrine Subscale (ES) | Change from baseline in Endocrine Symptom Subscale (ES)) in the ITT population at 24 weeks. ES score = the sum of the responses to all the questions on ES, low scores reflect poor quality of life and high scores reflects better quality of life. Score range: 0-72 | Assessed at baseline and after 24 weeks of treatment | 
| Anastrozole Plasma Concentrations (Cmin) | Trough Plasma concentrations (Cmin) of Anastrozole - only Anastrozole arm was evaluated for Trough Plasma concentrations. | Assessed at week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Breast Neoplasms, Tumors or cancer of the human BREAST, Tumor or cancer of the human MAMMARY GLAND