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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00605267

Enrollment

197

Registered

2008-01-31

Start date

2007-10-31

Completion date

2010-12-31

Last updated

2012-09-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Cancer

Keywords

Breast Cancer, Breast Neoplasms, Tumors or cancer of the human BREAST, Tumor or cancer of the human MAMMARY GLAND

Brief summary

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

Interventions

DRUGTamoxifen

20 mg once daily oral dose

DRUGAnastrazole (Arimidex)

1 mg once daily oral dose

DRUGGoserelin acetate (Zoladex)

3.6mg/month depot injection

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

FEMALE

Age

20 Years to No maximum

Healthy volunteers

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).

Design outcomes

Primary

Measure	Time frame	Description
Best Overall Response Rate (BORR) (Calliper)	24 weeks	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.
Best Overall Response Rate (BORR) (US)	24 weeks	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.
Best Overall Response Rate (BORR) (MRI/CT)	24 weeks	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.

Secondary

Measure	Time frame	Description
Bone Turnover Marker (BAP) CLEIA Method	Assessed at baseline and after 24 weeks of treatment	Change from baseline in serum Bone-Alkaline Phosphatase (BAP) at 24 weeks measured by CLEIA method
Bone Turnover Marker (NTX)	Assessed at baseline and after 24 weeks of treatment	Change from baseline in serum crosslinked N-Telopeptide of type I collagen (NTX) at 24 weeks
Serum Oestrone (E1) Concentrations	Assessed at baseline and after 24 weeks of treatment	Ratio of serum Oestrone (E1) concentration (pg/mL) in the ITT population from baseline at 24 weeks.
Serum Oestradiol (E2) Concentrations	Assessed at baseline and after 24 weeks of treatment	Ratio of serum Oestradiol (E2) concentration (pg/mL) in the ITT population from baseline at 24 weeks.
Oestrogen Receptor (ER) Status	Assessed at baseline and after 24 weeks of treatment	ER status in the ITT population is categorized as Positive or Negative
Bone Mineral Density (BMD) Lumbar Spine	Assessed at baseline and after 24 weeks of treatment	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.
Human Epidermal Growth Factor Receptor 2 (HER2) Status	Assessed at baseline and after 24 weeks of treatment	HER2 status in the ITT population is categorized as Positive or Negative
Histopathological Response Rate (HRR)	Assessed at baseline and after 24 weeks of treatment	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)
Functional Assessment of Cancer Therapy-Breast (FACT-B)	Assessed at baseline and after 24 weeks of treatment	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.
Endocrine Subscale (ES)	Assessed at baseline and after 24 weeks of treatment	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
Anastrozole Plasma Concentrations (Cmin)	Assessed at week 12	Trough Plasma concentrations (Cmin) of Anastrozole - only Anastrozole arm was evaluated for Trough Plasma concentrations.
Progesterone Receptor (PgR) Status	Assessed at baseline and after 24 weeks of treatment	PgR status in the ITT population is categorized as Positive or Negative.
Bone Mineral Density (BMD) Cervical Thighbone	Assessed at baseline and after 24 weeks of treatment	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.
Bone Turnover Marker (BAP) EIA Method	Assessed at baseline and after 24 weeks of treatment	Change from baseline in serum Bone-Alkaline Phosphatase (BAP) at 24 weeks measured by EIA method

Countries

Japan

Participant flow

Recruitment details

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

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.

Participants by arm

Arm	Count
Anastrozole 1 mg Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection	98
Tamoxifen 20 mg Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection	99
Total	197

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	0	1
Overall Study	Lack of Efficacy	1	5
Overall Study	Withdrawal by Subject	2	3

Baseline characteristics

Characteristic	Anastrozole 1 mg	Tamoxifen 20 mg	Total
Age, Customized 20-29 years	2 Participants	0 Participants	2 Participants
Age, Customized 30-39 years	21 Participants	20 Participants	41 Participants
Age, Customized 40-49 years	65 Participants	68 Participants	133 Participants
Age, Customized 50-59 years	10 Participants	11 Participants	21 Participants
Sex: Female, Male Female	98 Participants	99 Participants	197 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	87 / 98	84 / 98
serious Total, serious adverse events	1 / 98	0 / 98

Outcome results

Primary

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.

Time frame: 24 weeks

Population: 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

Arm	Measure	Value (NUMBER)
Anastrozole 1 mg	Best Overall Response Rate (BORR) (Calliper)	70.4 Percentage of Participants
Tamoxifen 20 mg	Best Overall Response Rate (BORR) (Calliper)	50.5 Percentage of Participants

Primary

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.

Time frame: 24 weeks

Arm	Measure	Value (NUMBER)
Anastrozole 1 mg	Best Overall Response Rate (BORR) (MRI/CT)	64.3 Percentage of Participants
Tamoxifen 20 mg	Best Overall Response Rate (BORR) (MRI/CT)	37.4 Percentage of Participants

Primary

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.

Time frame: 24 weeks

Arm	Measure	Value (NUMBER)
Anastrozole 1 mg	Best Overall Response Rate (BORR) (US)	58.2 Participants
Tamoxifen 20 mg	Best Overall Response Rate (BORR) (US)	42.4 Participants

Secondary

Anastrozole Plasma Concentrations (Cmin)

Trough Plasma concentrations (Cmin) of Anastrozole - only Anastrozole arm was evaluated for Trough Plasma concentrations.

Time frame: Assessed at week 12

Arm	Measure	Value (GEOMETRIC_MEAN)
Anastrozole 1 mg	Anastrozole Plasma Concentrations (Cmin)	29.7 ng/mL

Secondary

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.