Study of AMG 162 in Subjects With Advanced Cancer Currently Being Treated With Intravenous (IV) Bisphosphonates

This study has been completed.

Sponsor:

Information provided by:

Amgen

ClinicalTrials.gov Identifier:

NCT00104650

First received: March 3, 2005

Last updated: January 20, 2011

Last verified: January 2011

History of Changes

Results First Received: December 9, 2010

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Conditions:	Bone Metastases in Men With Hormone-Refractory Prostate Cancer Bone Metastases in Subjects With Advanced Breast Cancer Bone Metastases in Subjects With Advanced Cancer or Multiple Myeloma
Interventions:	Genetic: AMG 162 180 mg (SC) q 12 weeks Drug: IV Bisphosphonate q 4 weeks Genetic: AMG 162- 180 mg q 4 weeks

Participant Flow

Hide 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 enrolled from 2 December 2004 through 30 March 2007

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Bisphosphonate IV Q4W	Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)
Denosumab 180 mg Q12W	Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)
Denosumab 180 mg Q4W	Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)

Participant Flow for 2 periods

Period 1: Treatment Period (25 Weeks)

	Bisphosphonate IV Q4W	Denosumab 180 mg Q12W	Denosumab 180 mg Q4W
STARTED	37	36	38
Received Investigational Product	35	35	38
COMPLETED	25	25	28
NOT COMPLETED	12	11	10
Physician Decision	0	0	1
Withdrawal by Subject	2	1	1
Death	7	5	6
Disease progression	2	3	2
Ineligibility determined	0	1	0
Other	1	0	0
Protocol deviation	0	1	0

Period 2: Follow-up Period

	Bisphosphonate IV Q4W	Denosumab 180 mg Q12W	Denosumab 180 mg Q4W
STARTED	25	25	28
COMPLETED	14	12	18
NOT COMPLETED	11	13	10
Physician Decision	1	1	0
Adverse Event	1	0	1
Withdrawal by Subject	0	3	3
Death	6	6	4
Disease progression	3	1	0
Lost to Follow-up	0	1	2
Other	0	1	0

Baseline Characteristics

Hide Baseline Characteristics

Reporting Groups

	Description
Denosumab 180 mg Q4W	Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)
Bisphosphonate IV Q4W	Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)
Denosumab 180 mg Q12W	Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)
Total	Total of all reporting groups

Baseline Measures

	Denosumab 180 mg Q4W	Bisphosphonate IV Q4W	Denosumab 180 mg Q12W	Total
Number of Participants [units: participants]	38	37	36	111
Age [units: Years] Mean ± Standard Deviation	60.6 ± 10.7	61.6 ± 11.7	65.3 ± 12.7	62.5 ± 11.8
Gender [units: Participants]
Female	19	18	19	56
Male	19	19	17	55
Race/Ethnicity, Customized [units: Participants]
White or Caucasian	22	22	19	63
Black or African American	0	0	1	1
Hispanic or Latino	16	13	15	44
Asian	0	1	0	1
Native Hawaiian or Other Pacific Islander	0	1	0	1
Other	0	0	1	1
Cancer Type Stratification Factor [units: Participants]
Breast cancer	16	16	14	46
Prostate cancer	17	17	16	50
Mutiple myeloma	2	3	4	9
Other solid tumor	3	1	2	6
Urinary N-telopeptide (uNTx) Level ^[1] [units: nmol/mmol] Mean ± Standard Deviation	149.94 ± 147.20	149.88 ± 176.28	175.15 ± 208.87	158.01 ± 177.11
Serum C-Telopeptide (CTx) [units: ng/mL] Mean ± Standard Deviation	1.12 ± 1.18	1.40 ± 1.93	1.34 ± 1.27	1.28 ± 1.48

[1]	Corrected for urine creatinine (uNTx/Creatinine)

Outcome Measures

Show All Outcome Measures

1. Primary:

uNTx (Corrected by Creatinine) < 50 Nmol/mmol at Week 13 [ Time Frame: 13 weeks ]

Show Outcome Measure 1

2. Secondary:

uNTx (Corrected by Creatinine) < 50 Nmol/mmol at Week 25 [ Time Frame: 25 weeks ]

Show Outcome Measure 2

3. Secondary:

Percent Change of uNTx (Corrected by Creatinne) From Baseline to Week 25 [ Time Frame: Baseline, week 25 ]

Show Outcome Measure 3

4. Secondary:

Time to Reduction of uNTX (Corrected by Creatinine) to <50nmol/mmol [ Time Frame: Day 1, week 25 ]

Show Outcome Measure 4

5. Secondary:

Duration of Maintaining uNTX (Corrected by Creatinine) < 50nmol/mmol [ Time Frame: Day 1, week 25 ]

Show Outcome Measure 5

6. Secondary:

Percent Change of Serum CTX From Baseline to Week 25 [ Time Frame: Baseline, week 25 ]

Show Outcome Measure 6

7. Secondary:

Time to First Skeletal Related Event [ Time Frame: Day 1, week 25 ]

Show Outcome Measure 7

8. Secondary:

Skeletal Related Events [ Time Frame: Day 1, week 25 ]

Show Outcome Measure 8

9. Secondary:

Hypercalcemia [ Time Frame: Day 1, week 25 ]

Show Outcome Measure 9

Serious Adverse Events

Hide Serious Adverse Events

Time Frame	25 weeks
Additional Description	The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.

Reporting Groups

	Description
Bisphosphonate IV Q4W	No text entered.
Denosumab 180 mg Q12W	No text entered.
Denosumab 180 mg Q4W	No text entered.

Serious Adverse Events

	Bisphosphonate IV Q4W	Denosumab 180 mg Q12W	Denosumab 180 mg Q4W
Total, serious adverse events
# participants affected / at risk	19/35 (54.29%)	16/35 (45.71%)	21/38 (55.26%)
Blood and lymphatic system disorders
Anaemia ^{† 1}
# participants affected / at risk	4/35 (11.43%)	4/35 (11.43%)	4/38 (10.53%)
Bone marrow failure ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Coagulopathy ^{† 1}
# participants affected / at risk	0/35 (0.00%)	0/35 (0.00%)	1/38 (2.63%)
Leukopenia ^{† 1}
# participants affected / at risk	2/35 (5.71%)	0/35 (0.00%)	0/38 (0.00%)
Neutropenia ^{† 1}
# participants affected / at risk	2/35 (5.71%)	2/35 (5.71%)	2/38 (5.26%)
Thrombocytopenia ^{† 1}
# participants affected / at risk	2/35 (5.71%)	2/35 (5.71%)	3/38 (7.89%)
Cardiac disorders
Cardio-respiratory arrest ^{† 1}
# participants affected / at risk	0/35 (0.00%)	0/35 (0.00%)	1/38 (2.63%)
Cardiopulmonary failure ^{† 1}
# participants affected / at risk	2/35 (5.71%)	0/35 (0.00%)	0/38 (0.00%)
Pericardial effusion ^{† 1}
# participants affected / at risk	0/35 (0.00%)	1/35 (2.86%)	0/38 (0.00%)
Sinus bradycardia ^{† 1}
# participants affected / at risk	0/35 (0.00%)	0/35 (0.00%)	1/38 (2.63%)
Eye disorders
Diplopia ^{† 1}
# participants affected / at risk	0/35 (0.00%)	0/35 (0.00%)	1/38 (2.63%)
Gastrointestinal disorders
Abdominal distension ^{† 1}
# participants affected / at risk	0/35 (0.00%)	0/35 (0.00%)	1/38 (2.63%)
Ascites ^{† 1}
# participants affected / at risk	0/35 (0.00%)	1/35 (2.86%)	0/38 (0.00%)
Constipation ^{† 1}
# participants affected / at risk	0/35 (0.00%)	2/35 (5.71%)	0/38 (0.00%)
Diarrhoea ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Nausea ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Stomatitis ^{† 1}
# participants affected / at risk	2/35 (5.71%)	0/35 (0.00%)	0/38 (0.00%)
Subileus ^{† 1}
# participants affected / at risk	0/35 (0.00%)	1/35 (2.86%)	0/38 (0.00%)
Upper gastrointestinal haemorrhage ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	1/38 (2.63%)
General disorders
Death ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
General physical health deterioration ^{† 1}
# participants affected / at risk	1/35 (2.86%)	3/35 (8.57%)	1/38 (2.63%)
Obstruction ^{† 1}
# participants affected / at risk	0/35 (0.00%)	0/35 (0.00%)	1/38 (2.63%)
Pain ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Pyrexia ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	1/38 (2.63%)
Hepatobiliary disorders
Cholangitis acute ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Hepatic failure ^{† 1}
# participants affected / at risk	0/35 (0.00%)	1/35 (2.86%)	1/38 (2.63%)
Hepatomegaly ^{† 1}
# participants affected / at risk	0/35 (0.00%)	1/35 (2.86%)	0/38 (0.00%)
Infections and infestations
Bronchopneumonia ^{† 1}
# participants affected / at risk	0/35 (0.00%)	0/35 (0.00%)	1/38 (2.63%)
Catheter related infection ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Lung infection ^{† 1}
# participants affected / at risk	2/35 (5.71%)	1/35 (2.86%)	0/38 (0.00%)
Pneumonia ^{† 1}
# participants affected / at risk	2/35 (5.71%)	1/35 (2.86%)	1/38 (2.63%)
Pneumonia bacterial ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Staphylococcal sepsis ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Urinary tract infection staphylococcal ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Injury, poisoning and procedural complications
Brain contusion ^{† 1}
# participants affected / at risk	0/35 (0.00%)	1/35 (2.86%)	0/38 (0.00%)
Femoral neck fracture ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Subdural haematoma ^{† 1}
# participants affected / at risk	0/35 (0.00%)	2/35 (5.71%)	1/38 (2.63%)
Metabolism and nutrition disorders
Anorexia ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Cachexia ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Dehydration ^{† 1}
# participants affected / at risk	1/35 (2.86%)	2/35 (5.71%)	0/38 (0.00%)
Hypercalcaemia ^{† 1}
# participants affected / at risk	0/35 (0.00%)	1/35 (2.86%)	0/38 (0.00%)
Hypocalcaemia ^{† 1}
# participants affected / at risk	0/35 (0.00%)	0/35 (0.00%)	1/38 (2.63%)
Hypophosphataemia ^{† 1}
# participants affected / at risk	0/35 (0.00%)	0/35 (0.00%)	1/38 (2.63%)
Musculoskeletal and connective tissue disorders
Back pain ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Bone pain ^{† 1}
# participants affected / at risk	3/35 (8.57%)	2/35 (5.71%)	1/38 (2.63%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer ^{† 1}
# participants affected / at risk	0/35 (0.00%)	1/35 (2.86%)	1/38 (2.63%)
Malignant neoplasm progression ^{† 1}
# participants affected / at risk	0/35 (0.00%)	0/35 (0.00%)	1/38 (2.63%)
Metastases to bone ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Metastases to central nervous system ^{† 1}
# participants affected / at risk	3/35 (8.57%)	0/35 (0.00%)	2/38 (5.26%)
Metastases to liver ^{† 1}
# participants affected / at risk	0/35 (0.00%)	1/35 (2.86%)	0/38 (0.00%)
Metastases to lung ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Metastases to meninges ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	1/38 (2.63%)
Metastasis ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Multiple myeloma ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Prostate cancer ^{† 1}
# participants affected / at risk	2/35 (5.71%)	2/35 (5.71%)	3/38 (7.89%)
Prostate cancer metastatic ^{† 1}
# participants affected / at risk	0/35 (0.00%)	0/35 (0.00%)	1/38 (2.63%)
Thyroid cancer ^{† 1}
# participants affected / at risk	0/35 (0.00%)	1/35 (2.86%)	0/38 (0.00%)
Vaginal cancer metastatic ^{† 1}
# participants affected / at risk	0/35 (0.00%)	1/35 (2.86%)	0/38 (0.00%)
Nervous system disorders
Areflexia ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Cerebral haemorrhage ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	1/38 (2.63%)
Cerebrovascular accident ^{† 1}
# participants affected / at risk	0/35 (0.00%)	1/35 (2.86%)	0/38 (0.00%)
Epiduritis ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Facial paresis ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Loss of consciousness ^{† 1}
# participants affected / at risk	0/35 (0.00%)	0/35 (0.00%)	1/38 (2.63%)
Spinal cord compression ^{† 1}
# participants affected / at risk	2/35 (5.71%)	0/35 (0.00%)	0/38 (0.00%)
Psychiatric disorders
Anxiety ^{† 1}
# participants affected / at risk	0/35 (0.00%)	0/35 (0.00%)	1/38 (2.63%)
Confusional state ^{† 1}
# participants affected / at risk	2/35 (5.71%)	1/35 (2.86%)	0/38 (0.00%)
Hallucination ^{† 1}
# participants affected / at risk	0/35 (0.00%)	1/35 (2.86%)	0/38 (0.00%)
Renal and urinary disorders
Dysuria ^{† 1}
# participants affected / at risk	0/35 (0.00%)	0/35 (0.00%)	1/38 (2.63%)
Haematuria ^{† 1}
# participants affected / at risk	0/35 (0.00%)	0/35 (0.00%)	1/38 (2.63%)
Kidney enlargement ^{† 1}
# participants affected / at risk	0/35 (0.00%)	0/35 (0.00%)	1/38 (2.63%)
Renal failure ^{† 1}
# participants affected / at risk	1/35 (2.86%)	1/35 (2.86%)	1/38 (2.63%)
Renal failure acute ^{† 1}
# participants affected / at risk	0/35 (0.00%)	1/35 (2.86%)	0/38 (0.00%)
Renal tubular necrosis ^{† 1}
# participants affected / at risk	0/35 (0.00%)	0/35 (0.00%)	1/38 (2.63%)
Urinary retention ^{† 1}
# participants affected / at risk	0/35 (0.00%)	0/35 (0.00%)	1/38 (2.63%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema ^{† 1}
# participants affected / at risk	0/35 (0.00%)	1/35 (2.86%)	0/38 (0.00%)
Acute respiratory distress syndrome ^{† 1}
# participants affected / at risk	0/35 (0.00%)	0/35 (0.00%)	1/38 (2.63%)
Asthma ^{† 1}
# participants affected / at risk	0/35 (0.00%)	1/35 (2.86%)	0/38 (0.00%)
Dyspnoea ^{† 1}
# participants affected / at risk	0/35 (0.00%)	1/35 (2.86%)	1/38 (2.63%)
Pleurisy ^{† 1}
# participants affected / at risk	0/35 (0.00%)	1/35 (2.86%)	0/38 (0.00%)
Pulmonary embolism ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Respiratory distress ^{† 1}
# participants affected / at risk	2/35 (5.71%)	0/35 (0.00%)	0/38 (0.00%)
Skin and subcutaneous tissue disorders
Scar ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Surgical and medical procedures
Radiotherapy to bone ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Vascular disorders
Hypertension ^{† 1}
# participants affected / at risk	0/35 (0.00%)	1/35 (2.86%)	0/38 (0.00%)
Neurogenic shock ^{† 1}
# participants affected / at risk	1/35 (2.86%)	0/35 (0.00%)	0/38 (0.00%)
Thrombosis ^{† 1}
# participants affected / at risk	0/35 (0.00%)	0/35 (0.00%)	1/38 (2.63%)

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

Other Adverse Events

Show Other Adverse Events

More Information

Hide More Information

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: 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.

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: Study Director
Organization: Amgen Inc.
phone: 866-572-6436

Publications of Results:

Fizazi K, Lipton A, Mariette X, Body JJ, Rahim Y, Gralow JR, Gao G, Wu L, Sohn W, Jun S. Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. J Clin Oncol. 2009 Apr 1;27(10):1564-71. Epub 2009 Feb 23.

Fizazi K, Bosserman L, Gao G, Skacel T, Markus R. Denosumab treatment of prostate cancer with bone metastases and increased urine N-telopeptide levels after therapy with intravenous bisphosphonates: results of a randomized phase II trial. J Urol. 2009 Aug;182(2):509-15; discussion 515-6. Epub 2009 Jun 13.

Publications automatically indexed to this study:

Fizazi K, Bosserman L, Gao G, Skacel T, Markus R. Denosumab treatment of prostate cancer with bone metastases and increased urine N-telopeptide levels after therapy with intravenous bisphosphonates: results of a randomized phase II trial. J Urol. 2013 Jan;189(1 Suppl):S51-7; discussion S57-8. doi: 10.1016/j.juro.2012.11.022.

Responsible Party:	Global Development Leader, Amgen Inc.
ClinicalTrials.gov Identifier:	NCT00104650 History of Changes
Obsolete Identifiers:	NCT00121342
Other Study ID Numbers:	20040114
Study First Received:	March 3, 2005
Results First Received:	December 9, 2010
Last Updated:	January 20, 2011
Health Authority:	Canada: Health Canada European Union: European Medicines Agency France: Ministry of Health Mexico: Ministry of Health Poland: Drug Institut United States: Food and Drug Administration United States: Western Institutional Review Board Belgium: Pharmaceutical Inspectorate

To Top