Liver Safety under upfront Arimidex vs Tamoxifen - HEART

Study identifier:D5392L00023

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Prospective, Randomized, Multicentre, Comparative and Open-label Study on Hepatotoxicity of ARIMIDEX Compared with Tamoxifen in Adjuvant Therapy in Postmenopausal Women with Hormone Receptor+ Early Breast Cancer

Medical condition

Breast Cancer

Phase

Phase 4

Healthy volunteers

Study drug

Anastrozole, Tamoxifen

Sex

Female

Actual Enrollment

353

Study type

Interventional

Age

N/A

Date

Study Start Date: 01 Sept 2007

Primary Completion Date: 01 Dec 2011

Study Completion Date: 01 Dec 2011

Study design

Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Health Services Research

Verification:

Verified 01 Dec 2012 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Guangzhou, Guangdong, China

Location

Research Site

Shanghai, Shanghai, China

Location

Research Site

Tianjin, China

Location

Research Site

JINAN, Shandong, China

Location

Research Site

Dalian, Liaoning, China

Location

Research Site

CHENGDU, Sichuan, China

Location

Research Site

FUZHOU, Fujian, China

Location

Research Site

HANGZHOU, Zhejiang, China

Arms	Assigned Interventions
Experimental: 1 Anastrozole (ARIMIDEX)	Drug: Anastrozole 1 mg once daily oral dose Other Name: ARIMIDEX Other Name: ZD1033
Active Comparator: 2 Tamoxifen	Drug: Tamoxifen 20 mg once daily oral dose Other Name: NOLVADEX

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients were enrolled in 28 centres in the People's Republic of China. FSI: 18Sep2007; LSI: 28 Feb2009;LSLV:20 Dec 2011.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 384 patients were screened (informed consent signed and CRF started) and 353 patients were randomized with 175 patients in the Tamoxifen group and 178 in the Arimidex group.

Reporting Groups

	Description
Arimidex Group	Anastrozole(ARIMIDEX): 1 mg once daily oral dose
TAM Group	Tamoxifen : 20 mg once daily oral dose

Participant Flow: Overall Study

	Arimidex Group	TAM Group
STARTED	178	175
COMPLETED	149	114
NOT COMPLETED	29	61
Withdrawal by Subject	6	23
Adverse Event	8	15
Lost to Follow-up	9	15
Protocol Violation	2	6
Severe Non-Compliance to Protocol	4	2

Baseline Characteristics

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

Reporting Groups

	Description
Arimidex Group	Anastrozole(ARIMIDEX): 1 mg once daily oral dose
TAM Group	Tamoxifen : 20 mg once daily oral dose

Baseline Measures

	Arimidex Group	TAM Group	Total
Number of Participants [units: Participants]	178	175	353
Age Continuous [units: years] Mean ± Standard Deviation	59.7 ± 7.77	59.4 ± 8.84	59.6 ± 8.31
Gender, Male/Female [units: participants]
Female	178	175	353
Male	0	0	0

Outcome Measures

1. Primary Outcome Measure: Incidence of fatty liver disease [ Time Frame: At 48 weeks, 96 weeks, 144 weeks ]

Measure Type	Primary
Measure Name	Incidence of fatty liver disease
Measure Description	The primary objective is to compare ARIMIDEX (anastrozole) 1 mg once daily with Tamoxifen 20 mg once daily as adjuvant treatment in terms of: incidence of fatty liver diseases.
Time Frame	At 48 weeks, 96 weeks, 144 weeks
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
Arimidex Group	Anastrozole(ARIMIDEX): 1 mg once daily oral dose
TAM Group	Tamoxifen : 20 mg once daily oral dose

Measured Values

	Arimidex Group	TAM Group
Number of Participants Analyzed [units:participants]	178	175
Incidence of fatty liver disease [units: participants]
48 weeks	9	53
96 weeks	15	66
144 weeks	26	72

No statistical analysis provided for Incidence of fatty liver disease

2. Secondary Outcome Measure: Incidence of abnormal liver function [ Time Frame: At 48 weeks, 96 weeks, 144 weeks ]

Measure Type	Secondary
Measure Name	Incidence of abnormal liver function
Measure Description	The second objectives are to compare ARIMIDEX (anastrozole) 1 mg once daily with Tamoxifen 20 mg once daily as adjuvant treatment in terms of: incidences of abnormal liver function test, and time to treatment failure.
Time Frame	At 48 weeks, 96 weeks, 144 weeks
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
Arimidex Group	Anastrozole(ARIMIDEX): 1 mg once daily oral dose
TAM Group	Tamoxifen : 20 mg once daily oral dose

Measured Values

	Arimidex Group	TAM Group
Number of Participants Analyzed [units:participants]	178	175
Incidence of abnormal liver function [units: participants]
48 weeks	29	36
96 weeks	37	40
144 weeks	44	43

No statistical analysis provided for Incidence of abnormal liver function

3. Secondary Outcome Measure: Time to treatment failure [ Time Frame: Within 3 years ]

Measure Type	Secondary
Measure Name	Time to treatment failure
Measure Description
Time Frame	Within 3 years
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
Arimidex Group	Anastrozole(ARIMIDEX): 1 mg once daily oral dose
TAM Group	Tamoxifen : 20 mg once daily oral dose

Measured Values

	Arimidex Group	TAM Group
Number of Participants Analyzed [units:participants]	178	175
Time to treatment failure [units: days] Median (95% Confidence Interval)	1112 (1053 to N/A) ^[1]	454 (353 to 673)

No statistical analysis provided for Time to treatment failure

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
Arimidex Group	Anastrozole(ARIMIDEX): 1 mg once daily oral dose
TAM Group	Tamoxifen : 20 mg once daily oral dose

Serious Adverse Events

Arimidex Group

TAM Group

Total, serious adverse events

# participants affected / at risk

4/178 (2.25%)

4/175 (2.29%)

Injury, poisoning and procedural complications

Fall¹,^†

# participants affected / at risk

1/178 (0.56%)

0/175 (0.00%)

Injury, poisoning and procedural complications

Joint dislocation¹,^†

# participants affected / at risk

1/178 (0.56%)

0/175 (0.00%)

Injury, poisoning and procedural complications

Spinal fracture¹,^†

# participants affected / at risk

1/178 (0.56%)

0/175 (0.00%)

Infections and infestations

Cervicitis¹,^†

# participants affected / at risk

0/178 (0.00%)

2/175 (1.14%)

Cardiac disorders

Cardiac failure¹,^†

# participants affected / at risk

1/178 (0.56%)

0/175 (0.00%)

Cardiac disorders

Supraventricular extrasystoles¹,^†

# participants affected / at risk

0/178 (0.00%)

1/175 (0.57%)

Reproductive system and breast disorders

Uterine atony¹,^†

# participants affected / at risk

0/178 (0.00%)

1/175 (0.57%)

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

Cyst¹,^†

# participants affected / at risk

0/178 (0.00%)

1/175 (0.57%)

Hepatobiliary disorders

Hepatic cyst¹,^†

# participants affected / at risk

1/178 (0.56%)

0/175 (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	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	2%

Reporting Groups

	Description
Arimidex Group	Anastrozole(ARIMIDEX): 1 mg once daily oral dose
TAM Group	Tamoxifen : 20 mg once daily oral dose

Other Adverse Events

Arimidex Group

TAM Group

Total, other (not including serious) adverse events

# participants affected / at risk

39/178 (21.91%)

41/175 (23.43%)

Reproductive system and breast disorders

Endometrial Hypertrophy¹,^†

# participants affected / at risk

0/178 (0.00%)

10/175 (5.71%)

Reproductive system and breast disorders

Vaginal discharge¹,^†

# participants affected / at risk

1/178 (0.56%)

9/175 (5.14%)

Reproductive system and breast disorders

Vaginal haemorrhage¹,^†

# participants affected / at risk

1/178 (0.56%)

5/175 (2.86%)

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

11/178 (6.18%)

2/175 (1.14%)

Musculoskeletal and connective tissue disorders

Musculoskeletal pain¹,^†

# participants affected / at risk

6/178 (3.37%)

1/175 (0.57%)

Musculoskeletal and connective tissue disorders

Bone pain¹,^†

# participants affected / at risk

6/178 (3.37%)

0/175 (0.00%)

Gastrointestinal disorders

Abdominal discomfort¹,^†

# participants affected / at risk

3/178 (1.69%)

4/175 (2.29%)

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

6/178 (3.37%)

7/175 (4.00%)

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

5/178 (2.81%)

3/175 (1.71%)

†	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:	James J. Armbrust
Organization:	AstraZeneca
Phone	+44 1625 518062
E-mail:	[email protected]

Documents available

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=380&filename=CSR-D5392L00023.pdf
Download
CSR-D5392L00023.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca China Clinical Study

+86 21 52564555*5030

ClinicalTrialTransparency@astrazeneca.com

Investigators

Principal Investigator

Vivian Gu

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=380&filename=CSR-D5392L00023.pdf

CSR-D5392L00023.pdf

Trial Results Summaries