Arthralgia during anastrozole therapy for breast cancer

Study identifier:D5392L00013

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Multicentre, Open Study Assessing Joint Disorders Under ARIMIDEX® (1mg/day) as Adjuvant Treatment in Post Menopausal Women with Early Breast Cancer

Medical condition

Early Breast Cancer

Phase

Phase 4

Healthy volunteers

Study drug

Anastrozole

Sex

Female

Actual Enrollment

114

Study type

Interventional

Age

18 Years +

Date

Study Start Date: 01 Jun 2006

Primary Completion Date: 01 Jan 2009

Study Completion Date: 01 Jan 2009

Study design

Allocation: Non-randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2012 by AstraZeneca Pharmaceuticals

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Bordeaux, France

Location

Research Site

Caen, France

Location

Research Site

Paris, France

Location

Research Site

Poitiers, France

Location

Research Site

Lyon, France

Arms	Assigned Interventions

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 included by an investigator-oncologist between 15 June 2006 and 31 December 2007

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients were included by an investigator-oncologist who followed them up every 3 months over a period of one year (i.e., 5 visits). An investigator rheumatologist carried out the rheumatological evaluations at inclusion and then every 6 months over a period of one year (i.e., 3 visits)

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole 1 mg once daily

Participant Flow: Overall Study

	Anastrozole 1 mg
STARTED	114
Safety population	110^[1]
COMPLETED	106^[2]
NOT COMPLETED	8
Adverse Event	2
Withdrawal by Subject	2
Protocol Violation	3
house moving	1

[1]	Patients who taken at least one dose of treatment
[2]	with at least 1 evaluation for primary efficacy endpoint

Baseline Characteristics

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

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole 1 mg once daily

Baseline Measures

	Anastrozole 1 mg
Number of Participants [units: Participants]	106
Age Continuous [units: year] Mean ± Standard Deviation	62.87 ± 6.87
Gender, Male/Female [units: Participants]
Female	106
Male	0

Outcome Measures

1. Primary Outcome Measure: Number of participants with new events of arthralgia [ Time Frame: 12 months ]

Measure Type	Primary
Measure Name	Number of participants with new events of arthralgia
Measure Description
Time Frame	12 months
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 1 mg once daily

Measured Values

	Anastrozole 1 mg
Number of Participants Analyzed [units:participants]	106
Number of participants with new events of arthralgia [units: Participants]	37

No statistical analysis provided for Number of participants with new events of arthralgia

2. Secondary Outcome Measure: Functional Index of Cochin at 12 months in patients under anastrozole. [ Time Frame: 12 months ]

Measure Type	Secondary
Measure Name	Functional Index of Cochin at 12 months in patients under anastrozole.
Measure Description	Functional index of cochin score (from 0 to 90) : sum up of 18 questions on activities involving hands (each question scored from 0 = yes without difficulties (best) to 5 = impossible (worst)) based on 99 patients due to missing values.
Time Frame	12 months
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 1 mg once daily

Measured Values

	Anastrozole 1 mg
Number of Participants Analyzed [units:participants]	99
Functional Index of Cochin at 12 months in patients under anastrozole. [units: Units on scale] Mean (Standard Deviation)	4.32 (9.46)

No statistical analysis provided for Functional Index of Cochin at 12 months in patients under anastrozole.

3. Secondary Outcome Measure: Serum collagen degradation type I - CTX-I at 12 months in patients under anastrozole [ Time Frame: 12 months ]

Measure Type	Secondary
Measure Name	Serum collagen degradation type I - CTX-I at 12 months in patients under anastrozole
Measure Description	Results are based on 97 patients due to missing values
Time Frame	12 months
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 1 mg once daily

Measured Values

	Anastrozole 1 mg
Number of Participants Analyzed [units:participants]	97
Serum collagen degradation type I - CTX-I at 12 months in patients under anastrozole [units: Ng/mL] Mean (Standard Deviation)	0.5 (0.28)

No statistical analysis provided for Serum collagen degradation type I - CTX-I at 12 months in patients under anastrozole

4. Secondary Outcome Measure: Kellgren and Lawrence score at 12 months in patients under anastrozole [ Time Frame: 12 months ]

Measure Type	Secondary
Measure Name	Kellgren and Lawrence score at 12 months in patients under anastrozole
Measure Description	X ray evaluation of arthritis in 30 articulations ; each articulation scored from (0 = no arthritis to 4 = severe arthritis) based on 92 patients due to missing values
Time Frame	12 months
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 1 mg once daily

Measured Values

	Anastrozole 1 mg
Number of Participants Analyzed [units:participants]	92
Kellgren and Lawrence score at 12 months in patients under anastrozole [units: Units on scale] Mean (Standard Deviation)	12.66 (13.64)

No statistical analysis provided for Kellgren and Lawrence score at 12 months in patients under anastrozole

5. Secondary Outcome Measure: Synovial membrane thickness at 12 months in patients under anastrozole [ Time Frame: 12 months ]

Measure Type	Secondary
Measure Name	Synovial membrane thickness at 12 months in patients under anastrozole
Measure Description	X ray assessment on hands and wrists based on 99 patients due to missing values
Time Frame	12 months
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 1 mg once daily

Measured Values

	Anastrozole 1 mg
Number of Participants Analyzed [units:participants]	99
Synovial membrane thickness at 12 months in patients under anastrozole [units: millimeter] Median (Standard Deviation)	1.77 (0.62)

No statistical analysis provided for Synovial membrane thickness at 12 months in patients under anastrozole

6. Secondary Outcome Measure: Percentage of participant with therapeutic maintenance under anastrozole [ Time Frame: 12 months ]

Measure Type	Secondary
Measure Name	Percentage of participant with therapeutic maintenance under anastrozole
Measure Description	Treatment compliance. results based on 109 patients due to missing values
Time Frame	12 months
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 1 mg once daily

Measured Values

	Anastrozole 1 mg
Number of Participants Analyzed [units:participants]	109
Percentage of participant with therapeutic maintenance under anastrozole [units: percentage of participants]	80.7

No statistical analysis provided for Percentage of participant with therapeutic maintenance under anastrozole

Serious Adverse Events

Time Frame	No text entered.
Additional Description	110 participants were included in the safety population, those who had taken at least one dose of treatment

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole 1 mg once daily

Serious Adverse Events

Anastrozole 1 mg

Total, serious adverse events

# participants affected / at risk

6/110 (5.45%)

General disorders

Sudden death unexplained¹,^†

# participants affected / at risk

1/110 (0.91%)

Infections and infestations

Lymphangitis¹,^†

# participants affected / at risk

1/110 (0.91%)

Respiratory, thoracic and mediastinal disorders

Pneumopathy¹,^†

# participants affected / at risk

1/110 (0.91%)

Renal and urinary disorders

Calculus urinary bladder¹,^†

# participants affected / at risk

1/110 (0.91%)

Psychiatric disorders

Depression worsened¹,^†

# participants affected / at risk

1/110 (0.91%)

General disorders

General body pain¹,^†

# participants affected / at risk

1/110 (0.91%)

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

Parathyroid adenoma¹,^†

# participants affected / at risk

1/110 (0.91%)

Injury, poisoning and procedural complications

Femur fracture¹,^†

# participants affected / at risk

1/110 (0.91%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 11.0
2	Term from vocabulary,

Other Adverse Events

Time Frame	No text entered.
Additional Description	110 participants were included in the safety population, those who had taken at least one dose of treatment

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Anastrozole 1 mg	Anastrozole 1 mg once daily

Other Adverse Events

Anastrozole 1 mg

Total, other (not including serious) adverse events

# participants affected / at risk

106/110 (96.36%)

Musculoskeletal and connective tissue disorders

arthralgia¹,^†

# participants affected / at risk

59/110 (53.64%)

Vascular disorders

hot flush²,^†

# participants affected / at risk

35/110 (31.82%)

Musculoskeletal and connective tissue disorders

pain in extremity²,^†

# participants affected / at risk

31/110 (28.18%)

General disorders

asthenia²,^†

# participants affected / at risk

17/110 (15.45%)

Musculoskeletal and connective tissue disorders

back pain²,^†

# participants affected / at risk

14/110 (12.73%)

Psychiatric disorders

insomnia²,^†

# participants affected / at risk

12/110 (10.91%)

Nervous system disorders

headache²,^†

# participants affected / at risk

11/110 (10.00%)

Ear and labyrinth disorders

vertigo²,^†

# participants affected / at risk

8/110 (7.27%)

Gastrointestinal disorders

abdominal pain upper²,^†

# participants affected / at risk

6/110 (5.45%)

Gastrointestinal disorders

nausea²,^†

# participants affected / at risk

10/110 (9.09%)

General disorders

fatigue²,^†

# participants affected / at risk

10/110 (9.09%)

Musculoskeletal and connective tissue disorders

musculoskeletal chest pain²,^†

# participants affected / at risk

7/110 (6.36%)

Musculoskeletal and connective tissue disorders

musculosketal pain²,^†

# participants affected / at risk

9/110 (8.18%)

Musculoskeletal and connective tissue disorders

neck pain²,^†

# participants affected / at risk

6/110 (5.45%)

Reproductive system and breast disorders

breast fibrosis²,^†

# participants affected / at risk

7/110 (6.36%)

Reproductive system and breast disorders

breast oedema²,^†

# participants affected / at risk

8/110 (7.27%)

Reproductive system and breast disorders

breast pain²,^†

# participants affected / at risk

8/110 (7.27%)

Skin and subcutaneous tissue disorders

erythema²,^†

# participants affected / at risk

7/110 (6.36%)

Vascular disorders

lymphoedema²,^†

# participants affected / at risk

6/110 (5.45%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 10.0
2	Term from vocabulary, MedDRA 11.0
3	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=379&filename=CSR-D5392L00013.pdf
Download
CSR-D5392L00013.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca France Medical Oncology Clinical Study Information

+33.1.41.29.40.00

Investigators

Principal Investigator

AstraZeneca France Medical Director

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=379&filename=CSR-D5392L00013.pdf

CSR-D5392L00013.pdf

Trial Results Summaries