AMG 162 in the Treatment of Bone Loss in Subjects Undergoing Aromatase Inhibitor Therapy for Non-metastatic Breast Cancer

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00089661
• Collaborator: (none)
• Enrollment: 252
• Arms: 2
• Actual Duration (Months): 55.8

Study Details

Study Description

Brief Summary

The purpose of this trial is to evaluate AMG 162 in the treatment of bone loss in subjects undergoing Aromatase Inhibitor Therapy for Non-metastatic Breast Cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer; Low Bone Mineral Density; Osteopenia	Drug: Placebo; Drug: AMG 162 / Denosumab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 252 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate AMG 162 in the Treatment of Bone Loss in Subjects Undergoing Aromatase Inhibitor Therapy for Non-metastatic Breast Cancer
• Actual Study Start Date: Oct 1, 2004
• Actual Primary Completion Date: May 11, 2007
• Actual Study Completion Date: May 27, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AMG 162 / Denosumab	Drug: AMG 162 / Denosumab; 60 mg (1.0 mL) administered subcutaneously every six months, beginning on Study Day 1, for a total treatment period of 24 months
Placebo Comparator: Placebo	Drug: Placebo; 60 mg (1.0 mL) administered subcutaneously every six months, beginning on Study Day 1, for a total treatment period of 24 months

Outcome Measures

Primary Outcome Measures

1. Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 [12 months]

   Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.

Secondary Outcome Measures

1. Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 6 [6 months]

   Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.

2. Total Hip Bone Mineral Density Percent Change From Baseline at Month 12 [12 months]

   Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.

3. Total Hip Bone Mineral Density Percent Change From Baseline at Month 6 [6 months]

   Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.

4. Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 12 [12 months]

   Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.

5. Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 6 [6 months]

   Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

• Histologically or cytologically confirmed adenocarcinoma of the breast

• Subjects with early stage disease who are estrogen receptor positive and who have completed their treatment pathway (surgery, chemo-therapy, radiation, and/or hormone therapy) and are currently on or will initiate aromatase inhibitor therapy, and are expected to stay on aromatase inhibitor therapy for the duration of the 24-month study

• All treatment pathway must be completed ≥ 4 weeks prior to study entry, and all acute toxic effect of any above therapy must be resolved to ≤ Grade 1 by National Cancer Institution (NCI) Common Terminology Criteria for Adverse Events (CTCAE)

• Female > 18 years of age

• ECOG Performance status 0 and 1

• Lumbar spine, total hip or femoral neck BMD equivalent to a t-score classification of -1.0 to -2.5

• Subject is willing and able to provide signed consent before any study-specific procedure

Other criteria also apply.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website
• Notice regarding posted summaries of trial results

Publications

• Ellis GK, Bone HG, Chlebowski R, Paul D, Spadafora S, Fan M, Kim D. Effect of denosumab on bone mineral density in women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer: subgroup analyses of a phase 3 study. Breast Cancer Res Treat. 2009 Nov;118(1):81-7. doi: 10.1007/s10549-009-0352-y. Epub 2009 Mar 24.
• Ellis GK, Bone HG, Chlebowski R, Paul D, Spadafora S, Smith J, Fan M, Jun S. Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol. 2008 Oct 20;26(30):4875-82. doi: 10.1200/JCO.2008.16.3832. Epub 2008 Aug 25.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00089661
• Other Study ID Numbers: 20040135
• First Posted: Aug 11, 2004
• Last Update Posted: Oct 17, 2018
• Last Verified: Sep 1, 2018

• Keywords provided by Amgen: Breast Cancer; Bone loss associated with Aromatase Inhibitor therapy (AIT) for non-metastatic BC; osteopenia; Low bone density
• Additional relevant MeSH terms: Breast Neoplasms; Bone Diseases, Metabolic; Denosumab

Study Results

Participant Flow

Arm/Group Title	Denosumab 60 mg Q6M	Placebo
Arm/Group Description
Period Title: Overall Study
STARTED	127	125
COMPLETED	106	99
NOT COMPLETED	21	26

Baseline Characteristics

Arm/Group Title	Denosumab 60 mg Q6M	Placebo	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	127	125	252
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	59.2 (8.9)	59.7 (9.7)	59.5 (9.3)
Sex: Female, Male (Count of Participants)
Female	127 100%	125 100%	252 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12
Description	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Subjects with non-missing baseline and >= 1 non-missing post-baseline evaluation. Using Last Observation Carried Forward as imputation.

Arm/Group Title	Denosumab 60 mg Q6M	Placebo
Arm/Group Description
Measure Participants	123	122
Least Squares Mean (95% Confidence Interval) [Percent Change from Baseline]	4.8	-.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg Q6M, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.5
	Confidence Interval	() 95%; 4.8 to 6.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 6
Description	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Denosumab 60 mg Q6M	Placebo
Arm/Group Description
Measure Participants	123	122
Least Squares Mean (95% Confidence Interval) [Percent Change from Baseline]	3.7	-.6

3. Secondary Outcome

Title	Total Hip Bone Mineral Density Percent Change From Baseline at Month 12
Description	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Denosumab 60 mg Q6M	Placebo
Arm/Group Description
Measure Participants	123	122
Least Squares Mean (95% Confidence Interval) [Percent Change from Baseline]	3.1	-.7

4. Secondary Outcome

Title	Total Hip Bone Mineral Density Percent Change From Baseline at Month 6
Description	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Denosumab 60 mg Q6M	Placebo
Arm/Group Description
Measure Participants	123	122
Least Squares Mean (95% Confidence Interval) [Percent Change from Baseline]	2.3	-.4

5. Secondary Outcome

Title	Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 12
Description	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Denosumab 60 mg Q6M	Placebo
Arm/Group Description
Measure Participants	123	122
Least Squares Mean (95% Confidence Interval) [Percent Change from Baseline]	1.9	-.6

6. Secondary Outcome

Title	Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 6
Description	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Denosumab 60 mg Q6M	Placebo
Arm/Group Description
Measure Participants	123	122
Least Squares Mean (95% Confidence Interval) [Percent Change from Baseline]	1.2	-.9

Adverse Events

Arm/Group Title	Placebo		Denosumab 60 mg Q6M
Arm/Group Description
All Cause Mortality
	Placebo		Denosumab 60 mg Q6M
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Denosumab 60 mg Q6M
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/120 (9.2%)		19/129 (14.7%)
Cardiac disorders
Acute myocardial infarction	0/120 (0%)		1/129 (0.8%)
Atrial fibrillation	1/120 (0.8%)		0/129 (0%)
Atrioventricular block second degree	0/120 (0%)		1/129 (0.8%)
Cardiac failure congestive	1/120 (0.8%)		0/129 (0%)
Myocardial infarction	0/120 (0%)		1/129 (0.8%)
Myocardial ischaemia	1/120 (0.8%)		0/129 (0%)
Endocrine disorders
Goitre	1/120 (0.8%)		0/129 (0%)
Gastrointestinal disorders
Colitis ischaemic	0/120 (0%)		1/129 (0.8%)
Diverticulum	0/120 (0%)		1/129 (0.8%)
Faecaloma	1/120 (0.8%)		0/129 (0%)
Gastrointestinal haemorrhage	0/120 (0%)		1/129 (0.8%)
Large intestine perforation	1/120 (0.8%)		0/129 (0%)
Small intestinal obstruction	0/120 (0%)		1/129 (0.8%)
General disorders
Pelvic mass	0/120 (0%)		1/129 (0.8%)
Hepatobiliary disorders
Cholecystitis	1/120 (0.8%)		1/129 (0.8%)
Cholelithiasis	2/120 (1.7%)		0/129 (0%)
Infections and infestations
Cellulitis	0/120 (0%)		1/129 (0.8%)
Diverticulitis	0/120 (0%)		1/129 (0.8%)
Labyrinthitis	0/120 (0%)		1/129 (0.8%)
Pneumonia	1/120 (0.8%)		0/129 (0%)
Injury, poisoning and procedural complications
Femoral neck fracture	1/120 (0.8%)		0/129 (0%)
Fracture	0/120 (0%)		1/129 (0.8%)
Incisional hernia	1/120 (0.8%)		0/129 (0%)
Musculoskeletal and connective tissue disorders
Arthritis	1/120 (0.8%)		1/129 (0.8%)
Intervertebral disc protrusion	0/120 (0%)		1/129 (0.8%)
Osteoarthritis	0/120 (0%)		2/129 (1.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign breast neoplasm	1/120 (0.8%)		0/129 (0%)
Benign ovarian tumour	0/120 (0%)		1/129 (0.8%)
Breast cancer in situ	0/120 (0%)		1/129 (0.8%)
Breast cancer metastatic	0/120 (0%)		1/129 (0.8%)
Colon adenoma	0/120 (0%)		1/129 (0.8%)
Malignant pleural effusion	0/120 (0%)		1/129 (0.8%)
Metastases to bone	1/120 (0.8%)		0/129 (0%)
Metastases to liver	1/120 (0.8%)		0/129 (0%)
Metastatic neoplasm	0/120 (0%)		1/129 (0.8%)
Uterine leiomyoma	0/120 (0%)		1/129 (0.8%)
Nervous system disorders
Transient ischaemic attack	1/120 (0.8%)		1/129 (0.8%)
Reproductive system and breast disorders
Rectocele	0/120 (0%)		1/129 (0.8%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/120 (0.8%)		0/129 (0%)
Pneumonitis	1/120 (0.8%)		0/129 (0%)
Respiratory failure	0/120 (0%)		1/129 (0.8%)
Other (Not Including Serious) Adverse Events
	Placebo		Denosumab 60 mg Q6M
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	108/120 (90%)		117/129 (90.7%)
Gastrointestinal disorders
Constipation	11/120 (9.2%)		15/129 (11.6%)
Diarrhoea	9/120 (7.5%)		5/129 (3.9%)
Gastrooesophageal reflux disease	8/120 (6.7%)		2/129 (1.6%)
Nausea	11/120 (9.2%)		10/129 (7.8%)
Vomiting	6/120 (5%)		8/129 (6.2%)
General disorders
Fatigue	17/120 (14.2%)		17/129 (13.2%)
Oedema peripheral	5/120 (4.2%)		8/129 (6.2%)
Infections and infestations
Bronchitis	7/120 (5.8%)		5/129 (3.9%)
Sinusitis	4/120 (3.3%)		9/129 (7%)
Upper respiratory tract infection	6/120 (5%)		10/129 (7.8%)
Urinary tract infection	5/120 (4.2%)		7/129 (5.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	30/120 (25%)		31/129 (24%)
Arthritis	6/120 (5%)		5/129 (3.9%)
Back pain	15/120 (12.5%)		18/129 (14%)
Bone pain	8/120 (6.7%)		5/129 (3.9%)
Muscle spasms	6/120 (5%)		7/129 (5.4%)
Musculoskeletal chest pain	6/120 (5%)		7/129 (5.4%)
Myalgia	5/120 (4.2%)		11/129 (8.5%)
Pain in extremity	14/120 (11.7%)		19/129 (14.7%)
Shoulder pain	4/120 (3.3%)		11/129 (8.5%)
Nervous system disorders
Headache	9/120 (7.5%)		11/129 (8.5%)
Hypoaesthesia	4/120 (3.3%)		7/129 (5.4%)
Psychiatric disorders
Anxiety	6/120 (5%)		8/129 (6.2%)
Depression	11/120 (9.2%)		7/129 (5.4%)
Insomnia	14/120 (11.7%)		12/129 (9.3%)
Reproductive system and breast disorders
Breast pain	6/120 (5%)		3/129 (2.3%)
Vulvovaginal dryness	3/120 (2.5%)		9/129 (7%)
Respiratory, thoracic and mediastinal disorders
Cough	5/120 (4.2%)		13/129 (10.1%)
Dyspnoea	5/120 (4.2%)		7/129 (5.4%)
Skin and subcutaneous tissue disorders
Rash	6/120 (5%)		10/129 (7.8%)
Vascular disorders
Hot flush	8/120 (6.7%)		7/129 (5.4%)
Hypertension	7/120 (5.8%)		2/129 (1.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multi-center studies, the investigator agrees not to publish any results before the first multi-center publication.