Arimidex/Tamoxifen neo adjuvant study in premenopausal patients with breast cancer under anti hormonal treatment

Study identifier:D539BC00001

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

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

Medical condition

Breast Cancer

Phase

Phase 3

Healthy volunteers

Study drug

Tamoxifen, Anastrazole (Arimidex), Goserelin acetate (Zoladex)

Sex

Female

Actual Enrollment

197

Study type

Interventional

Age

20 Years +

Date

Study Start Date: 01 Oct 2007

Primary Completion Date: 01 Nov 2009

Study Completion Date: 01 Dec 2010

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Aug 2012 by AstraZeneca Pharmaceuticals

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Osaka, Osaka, Japan

Location

Research Site

Hakata, Fukuoka, Japan

Location

Research Site

Kumamoto, Kumamoto, Japan

Location

Research Site

Nagoya, Nagoya, Japan

Arms	Assigned Interventions
Active Comparator: 1 Tamoxifen	Drug: Tamoxifen 20 mg once daily oral dose Other Name: NOLVADEX Drug: Goserelin acetate (Zoladex) 3.6mg/month depot injection Other Name: ZOLADEX
Experimental: 2 Anastrazole (Arimidex)	Drug: Anastrazole (Arimidex) 1 mg once daily oral dose Other Name: ARIMIDEX Other Name: ZD1033 Drug: Goserelin acetate (Zoladex) 3.6mg/month depot injection Other Name: ZOLADEX

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were recruited from 4 research sites in Japan: Hakata (Fukuoka), Kumamoto (Kumamoto), Nagoya (Nagoya), Osaka (Osaka). The study initiation date was October 2007 and the study completion date was January 2010.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 197 participants were recruited into this study and 98 were randomized to Anastrozole (20 mg once daily oral dose) and 99 were randomized to Tamoxifen (1 mg once daily oral dose) with one subject voluntarily discontinuing prior to receiving treatment Tamoxifen.

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Tamoxifen 20 mg	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection

Participant Flow: Overall Study

	Anastrozole 1 mg	Tamoxifen 20 mg
STARTED	98	99
COMPLETED	95^[1]	90^[2]
NOT COMPLETED	3	9
Adverse Event	0	1
Lack of Efficacy	1	5
Withdrawal by Subject	2	3

[1]	Breast surgery performed
[2]	Breast surgery performed

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Tamoxifen 20 mg	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection

Baseline Measures

	Anastrozole 1 mg	Tamoxifen 20 mg	Total
Number of Participants [units: Participants]	98	99	197
Age, Customized [units: Participants]
20-29 years	2	0	2
30-39 years	21	20	41
40-49 years	65	68	133
50-59 years	10	11	21
Gender, Male/Female [units: Participants]
Female	98	99	197
Male	0	0	0

Outcome Measures

1. Primary Outcome Measure: Best Overall Response Rate (BORR) (Calliper) [ Time Frame: 24 weeks ]

Measure Type	Primary
Measure Name	Best Overall Response Rate (BORR) (Calliper)
Measure Description	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.
Time Frame	24 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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. At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Tamoxifen 20 mg	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection

Measured Values

	Anastrozole 1 mg	Tamoxifen 20 mg
Number of Participants Analyzed [units:participants]	98	99
Best Overall Response Rate (BORR) (Calliper) [units: Percentage of Participants]	70.4	50.5

No statistical analysis provided for Best Overall Response Rate (BORR) (Calliper)

2. Primary Outcome Measure: Best Overall Response Rate (BORR) (US) [ Time Frame: 24 weeks ]

Measure Type	Primary
Measure Name	Best Overall Response Rate (BORR) (US)
Measure Description	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.
Time Frame	24 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Tamoxifen 20 mg	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection

Measured Values

	Anastrozole 1 mg	Tamoxifen 20 mg
Number of Participants Analyzed [units:participants]	98	99
Best Overall Response Rate (BORR) (US) [units: Participants]	58.2	42.4

No statistical analysis provided for Best Overall Response Rate (BORR) (US)

3. Primary Outcome Measure: Best Overall Response Rate (BORR) (MRI/CT) [ Time Frame: 24 weeks ]

Measure Type	Primary
Measure Name	Best Overall Response Rate (BORR) (MRI/CT)
Measure Description	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.
Time Frame	24 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Tamoxifen 20 mg	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection

Measured Values

	Anastrozole 1 mg	Tamoxifen 20 mg
Number of Participants Analyzed [units:participants]	98	99
Best Overall Response Rate (BORR) (MRI/CT) [units: Percentage of Participants]	64.3	37.4

No statistical analysis provided for Best Overall Response Rate (BORR) (MRI/CT)

4. Secondary Outcome Measure: Bone Mineral Density (BMD) lumbar spine [ Time Frame: Assessed at baseline and after 24 weeks of treatment ]

Measure Type	Secondary
Measure Name	Bone Mineral Density (BMD) lumbar spine
Measure Description	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.
Time Frame	Assessed at baseline and after 24 weeks of treatment
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The standard BMD value is defined by Japanese Osteoporosis Society in the table of reference values showing the mean for the age, gender, race, skeletal site, and densitometer measurement units was used. Then the formula was used at each measurement data: BMD(%) = Patient's BMD / standard BMD) x 100

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Tamoxifen 20 mg	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection

Measured Values

	Anastrozole 1 mg	Tamoxifen 20 mg
Number of Participants Analyzed [units:participants]	80	78
Bone Mineral Density (BMD) lumbar spine [units: PercentageBMD=Patient's BMD/standard BMD] Mean (Standard Deviation)	-5.8 (3.4)	-2.9 (2.5)

No statistical analysis provided for Bone Mineral Density (BMD) lumbar spine

5. Secondary Outcome Measure: Bone Mineral Density (BMD) cervical thighbone [ Time Frame: Assessed at baseline and after 24 weeks of treatment ]

Measure Type	Secondary
Measure Name	Bone Mineral Density (BMD) cervical thighbone
Measure Description	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.
Time Frame	Assessed at baseline and after 24 weeks of treatment
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Difference of percentage Bone Mineral Density (BMD) Cervical Thighbone = BMD percentage at 24 weeks – BMD percentage at baseline

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Tamoxifen 20 mg	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection

Measured Values

	Anastrozole 1 mg	Tamoxifen 20 mg
Number of Participants Analyzed [units:participants]	80	77
Bone Mineral Density (BMD) cervical thighbone [units: PercentageBMD=Patient'sBMD/standard BMD)] Mean (Standard Deviation)	-2.5 (5.1)	-0.5 (3.2)

No statistical analysis provided for Bone Mineral Density (BMD) cervical thighbone

6. Secondary Outcome Measure: Bone turnover marker (BAP) EIA method [ Time Frame: Assessed at baseline and after 24 weeks of treatment ]

Measure Type	Secondary
Measure Name	Bone turnover marker (BAP) EIA method
Measure Description	Change from baseline in serum Bone-Alkaline Phosphatase (BAP) at 24 weeks measured by EIA method
Time Frame	Assessed at baseline and after 24 weeks of treatment
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Tamoxifen 20 mg	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection

Measured Values

	Anastrozole 1 mg	Tamoxifen 20 mg
Number of Participants Analyzed [units:participants]	59	60
Bone turnover marker (BAP) EIA method [units: U/L] Mean (Standard Deviation)	7.1941 (6.1600)	0.7333 (3.3640)

No statistical analysis provided for Bone turnover marker (BAP) EIA method

7. Secondary Outcome Measure: Bone turnover marker (BAP) CLEIA method [ Time Frame: Assessed at baseline and after 24 weeks of treatment ]

Measure Type	Secondary
Measure Name	Bone turnover marker (BAP) CLEIA method
Measure Description	Change from baseline in serum Bone-Alkaline Phosphatase (BAP) at 24 weeks measured by CLEIA method
Time Frame	Assessed at baseline and after 24 weeks of treatment
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Tamoxifen 20 mg	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection

Measured Values

	Anastrozole 1 mg	Tamoxifen 20 mg
Number of Participants Analyzed [units:participants]	36	30
Bone turnover marker (BAP) CLEIA method [units: ug/L] Mean (Standard Deviation)	3.96 (4.60)	-0.75 (3.10)

No statistical analysis provided for Bone turnover marker (BAP) CLEIA method

8. Secondary Outcome Measure: Bone turnover marker (NTX) [ Time Frame: Assessed at baseline and after 24 weeks of treatment ]

Measure Type	Secondary
Measure Name	Bone turnover marker (NTX)
Measure Description	Change from baseline in serum crosslinked N-Telopeptide of type I collagen (NTX) at 24 weeks
Time Frame	Assessed at baseline and after 24 weeks of treatment
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Tamoxifen 20 mg	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection

Measured Values

	Anastrozole 1 mg	Tamoxifen 20 mg
Number of Participants Analyzed [units:participants]	95	89
Bone turnover marker (NTX) [units: nmolBCE(Bone Collagen Equivalent) /L] Mean (Standard Deviation)	9.17 (4.74)	2.59 (3.23)

No statistical analysis provided for Bone turnover marker (NTX)

9. Secondary Outcome Measure: Serum Oestrone (E1) Concentrations [ Time Frame: Assessed at baseline and after 24 weeks of treatment ]

Measure Type	Secondary
Measure Name	Serum Oestrone (E1) Concentrations
Measure Description	Ratio of serum Oestrone (E1) concentration (pg/mL) in the ITT population from baseline at 24 weeks.
Time Frame	Assessed at baseline and after 24 weeks of treatment
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Tamoxifen 20 mg	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection

Measured Values

	Anastrozole 1 mg	Tamoxifen 20 mg
Number of Participants Analyzed [units:participants]	96	92
Serum Oestrone (E1) Concentrations [units: Ratio] Mean (Standard Deviation)	0.028 (0.036)	0.341 (0.282)

No statistical analysis provided for Serum Oestrone (E1) Concentrations

10. Secondary Outcome Measure: Serum Oestradiol (E2) Concentrations [ Time Frame: Assessed at baseline and after 24 weeks of treatment ]

Measure Type	Secondary
Measure Name	Serum Oestradiol (E2) Concentrations
Measure Description	Ratio of serum Oestradiol (E2) concentration (pg/mL) in the ITT population from baseline at 24 weeks.
Time Frame	Assessed at baseline and after 24 weeks of treatment
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Tamoxifen 20 mg	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection

Measured Values

	Anastrozole 1 mg	Tamoxifen 20 mg
Number of Participants Analyzed [units:participants]	96	92
Serum Oestradiol (E2) Concentrations [units: Ratio] Mean (Standard Deviation)	0.041 (0.092)	0.082 (0.186)

No statistical analysis provided for Serum Oestradiol (E2) Concentrations

11. Secondary Outcome Measure: Oestrogen receptor (ER) status [ Time Frame: Assessed at baseline and after 24 weeks of treatment ]

Measure Type	Secondary
Measure Name	Oestrogen receptor (ER) status
Measure Description	ER status in the ITT population is categorized as Positive or Negative
Time Frame	Assessed at baseline and after 24 weeks of treatment
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Tamoxifen 20 mg	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection

Measured Values

	Anastrozole 1 mg	Tamoxifen 20 mg
Number of Participants Analyzed [units:participants]	94	90
Oestrogen receptor (ER) status [units: Participants]
Baseline Positive & 24 weeks Negative	2	1
Baseline Positive & 24 weeks Positive	92	89
Baseline Negative & 24 weeks Negative	0	0
Baseline Negative & 24 weeks Positive	0	0

No statistical analysis provided for Oestrogen receptor (ER) status

12. Secondary Outcome Measure: Progesterone receptor (PgR) status [ Time Frame: Assessed at baseline and after 24 weeks of treatment ]

Measure Type	Secondary
Measure Name	Progesterone receptor (PgR) status
Measure Description	PgR status in the ITT population is categorized as Positive or Negative.
Time Frame	Assessed at baseline and after 24 weeks of treatment
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Tamoxifen 20 mg	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection

Measured Values

	Anastrozole 1 mg	Tamoxifen 20 mg
Number of Participants Analyzed [units:participants]	94	90
Progesterone receptor (PgR) status [units: Participants]
Baseline Positive & 24 weeks Negative	60	19
Baseline Positive & 24 weeks Positive	29	59
Baseline Negative & 24 weeks Negative	4	9
Baseline Negative & 24 weeks Positive	1	3

No statistical analysis provided for Progesterone receptor (PgR) status

13. Secondary Outcome Measure: Human epidermal growth factor receptor 2 (HER2) status [ Time Frame: Assessed at baseline and after 24 weeks of treatment ]

Measure Type	Secondary
Measure Name	Human epidermal growth factor receptor 2 (HER2) status
Measure Description	HER2 status in the ITT population is categorized as Positive or Negative
Time Frame	Assessed at baseline and after 24 weeks of treatment
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Tamoxifen 20 mg	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection

Measured Values

	Anastrozole 1 mg	Tamoxifen 20 mg
Number of Participants Analyzed [units:participants]	94	90
Human epidermal growth factor receptor 2 (HER2) status [units: Participants]
Baseline Positive & 24 weeks Negative	0	0
Baseline Positive & 24 weeks Positive	0	0
Baseline Negative & 24 weeks Negative	92	88
Baseline Negative & 24 weeks Positive	2	2

No statistical analysis provided for Human epidermal growth factor receptor 2 (HER2) status

14. Secondary Outcome Measure: Histopathological response rate (HRR) [ Time Frame: Assessed at baseline and after 24 weeks of treatment ]

Measure Type	Secondary
Measure Name	Histopathological response rate (HRR)
Measure Description	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)
Time Frame	Assessed at baseline and after 24 weeks of treatment
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Tamoxifen 20 mg	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection

Measured Values

	Anastrozole 1 mg	Tamoxifen 20 mg
Number of Participants Analyzed [units:participants]	98	99
Histopathological response rate (HRR) [units: Percentage of Participants]	41.8	27.3

No statistical analysis provided for Histopathological response rate (HRR)

15. Secondary Outcome Measure: Functional Assessment of Cancer Therapy-Breast (FACT-B) [ Time Frame: Assessed at baseline and after 24 weeks of treatment ]

Measure Type	Secondary
Measure Name	Functional Assessment of Cancer Therapy-Breast (FACT-B)
Measure Description	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.
Time Frame	Assessed at baseline and after 24 weeks of treatment
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Total score of subscores or TOI is calculated from each score of question. Higher score means better and lower score means worthier. PWB, FWB and BCS were assessed in this study. TOI was a total of PWB, FWB and BCS.

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Tamoxifen 20 mg	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection

Measured Values

	Anastrozole 1 mg	Tamoxifen 20 mg
Number of Participants Analyzed [units:participants]	95	92
Functional Assessment of Cancer Therapy-Breast (FACT-B) [units: Trial Outcome Index (TOI) (Prorated)] Mean (Standard Deviation)	-4.42 (11.07)	-2.65 (8.09)

No statistical analysis provided for Functional Assessment of Cancer Therapy-Breast (FACT-B)

16. Secondary Outcome Measure: Endocrine Subscale (ES) [ Time Frame: Assessed at baseline and after 24 weeks of treatment ]

Measure Type	Secondary
Measure Name	Endocrine Subscale (ES)
Measure Description	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
Time Frame	Assessed at baseline and after 24 weeks of treatment
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Difference of Endocrine Subscale (ES) = ES at 24 weeks – ES at baseline.

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Tamoxifen 20 mg	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection

Measured Values

	Anastrozole 1 mg	Tamoxifen 20 mg
Number of Participants Analyzed [units:participants]	92	91
Endocrine Subscale (ES) [units: ES score] Mean (Standard Deviation)	-8.85 (8.69)	-6.27 (8.93)

No statistical analysis provided for Endocrine Subscale (ES)

17. Secondary Outcome Measure: Anastrozole plasma concentrations (Cmin) [ Time Frame: Assessed at week 12 ]

Measure Type	Secondary
Measure Name	Anastrozole plasma concentrations (Cmin)
Measure Description	Trough Plasma concentrations (Cmin) of Anastrozole - only Anastrozole arm was evaluated for Trough Plasma concentrations.
Time Frame	Assessed at week 12
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Tamoxifen 20 mg	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection

Measured Values

	Anastrozole 1 mg	Tamoxifen 20 mg
Number of Participants Analyzed [units:participants]	28	0
Anastrozole plasma concentrations (Cmin) [units: ng/mL] Geometric Mean (Full Range)	29.7 (17.3 to 52.4)

No statistical analysis provided for Anastrozole plasma concentrations (Cmin)

Serious Adverse Events

Time Frame	No text entered.
Additional Description	One subject voluntarily discontinued prior to receiving treatment to Tamoxifen

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Tamoxifen 20 mg	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection

Serious Adverse Events

Anastrozole 1 mg

Tamoxifen 20 mg

Total, serious adverse events

# participants affected / at risk

1/98 (1.02%)

0/98 (0.00%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign Neoplasm¹,^†

# participants affected / at risk

1/98 (1.02%)

0/98 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 10.0
2	Term from vocabulary,

Other Adverse Events

Time Frame	No text entered.
Additional Description	One subject voluntarily discontinued prior to receiving treatment to Tamoxifen

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Tamoxifen 20 mg	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection

Other Adverse Events

Anastrozole 1 mg

Tamoxifen 20 mg

Total, other (not including serious) adverse events

# participants affected / at risk

87/98 (88.78%)

84/98 (85.71%)

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

4/98 (4.08%)

13/98 (13.27%)

Gastrointestinal disorders

Abdominal Pain Upper¹,^†

# participants affected / at risk

5/98 (5.10%)

6/98 (6.12%)

General disorders

Fatigue¹,^†

# participants affected / at risk

4/98 (4.08%)

5/98 (5.10%)

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

27/98 (27.55%)

24/98 (24.49%)

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

35/98 (35.71%)

20/98 (20.41%)

Musculoskeletal and connective tissue disorders

Musculoskeletal Stiffness¹,^†

# participants affected / at risk

21/98 (21.43%)

9/98 (9.18%)

Musculoskeletal and connective tissue disorders

Joint Stiffness¹,^†

# participants affected / at risk

5/98 (5.10%)

1/98 (1.02%)

Musculoskeletal and connective tissue disorders

Myalgia¹,^†

# participants affected / at risk

5/98 (5.10%)

1/98 (1.02%)

Nervous system disorders

Headache¹,^†

# participants affected / at risk

20/98 (20.41%)

15/98 (15.31%)

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

3/98 (3.06%)

5/98 (5.10%)

Nervous system disorders

Hypoaesthesia¹,^†

# participants affected / at risk

5/98 (5.10%)

3/98 (3.06%)

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

7/98 (7.14%)

9/98 (9.18%)

Reproductive system and breast disorders

Menopausal Symptoms¹,^†

# participants affected / at risk

6/98 (6.12%)

4/98 (4.08%)

Reproductive system and breast disorders

Metrorrhagia¹,^†

# participants affected / at risk

5/98 (5.10%)

2/98 (2.04%)

Skin and subcutaneous tissue disorders

Hyperhidrosis¹,^†

# participants affected / at risk

4/98 (4.08%)

8/98 (8.16%)

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

5/98 (5.10%)

3/98 (3.06%)

Vascular disorders

Hot Flush¹,^†

# participants affected / at risk

51/98 (52.04%)

52/98 (53.06%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 10.0
2	Term from vocabulary,

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description:

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Gerard Lynch
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=381&filename=CSR-D539BC00001.pdf
Download
CSR-D539BC00001.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

Toshiyuki Kihara

81 6 6453 7996

T.Kihara@astrazeneca.com

Investigators

Principal Investigator

Toshiyuki Kihara

Clinical

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=381&filename=CSR-D539BC00001.pdf

CSR-D539BC00001.pdf

Trial Results Summaries