Study of Denosumab in the Treatment of Hypercalcemia of Malignancy in Subjects With Elevated Serum Calcium

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00896454
• Collaborator: (none)
• Enrollment: 33
• Locations: 24
• Arm: 1
• Actual Duration (Months): 45.1
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the potential of denosumab to treat Hypercalcemia of Malignancy in patients with elevated serum calcium who do not respond to recent treatment with intravenous bisphosphonates by lowering corrected serum calcium </= 11.5 mg/dL (2.9 millimoles /L) by day 10.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer; Hypercalcemia of Malignancy; Colon Cancer; Endocrine Cancer; Head and Neck Cancer; Kidney Cancer; Lung Cancer; Lymphoma; Metastatic Cancer; Multiple Myeloma; Parathyroid Neoplasms; Renal Cancer; Thyroid Cancer; Hodgkin's Lymphoma; Non-Hodgkin's Lymphoma; Non-Small Cell Lung Cancer	Drug: denosumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single-arm, Multicenter, Proof-of-concept Study of Denosumab in the Treatment of Hypercalcemia of Malignancy in Subjects With Elevated Serum Calcium Despite Recent Treatment With IV Bisphosphonates
• Actual Study Start Date: Nov 16, 2009
• Actual Primary Completion Date: Sep 13, 2012
• Actual Study Completion Date: Aug 21, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: denosumab Eligible subjects will receive denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study days 8 and 15.	Drug: denosumab; 120 mg subcutaneously (SC) every 4 weeks with a loading dose of 120 mg SC on study days 8 and 15.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With a Response Within 10 Days of First Dose of Denosumab [10 days]

   Response is defined as corrected serum calcium (CSC) ≤ 11.5 mg/dL, within 10 days after the first dose of denosumab. For all CSC values, if albumin was < 4 g/dL, the following formula was used to calculate CSC: CSC = Total serum calcium [mg/dL] + (0.8 x (4 - serum albumin [g/dL]))

Secondary Outcome Measures

1. Percentage of Participants With a Response by Visit [Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57]

   Response is defined as corrected serum calcium (CSC) ≤ 11.5 mg/dL, within 10 days after the first dose of denosumab. For all CSC values, if albumin was < 4 g/dL, the following formula was used to calculate CSC: CSC = Total serum calcium [mg/dL] + (0.8 x (4 - serum albumin [g/dL]))

2. Percentage of Participants With a Complete Response by Visit [Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57]

   Response is defined as corrected serum calcium (CSC) ≤ 10.8 mg/dL (2.7 mmol/L). For all CSC values, if albumin was < 4 g/dL, the following formula was used to calculate CSC: CSC = Total serum calcium [mg/dL] + (0.8 x (4 - serum albumin [g/dL])).

3. Time to Response [From Day 1 until the end of study date or primary data cutoff date (13 September 2012), whichever occured first; median time on study was 1.8 months.]

   Time to Response was defined as the time period from study Day 1 to the first time post-baseline corrected serum calcium (CSC) ≤ 11.5 mg/dL. Participants were censored on the last CSC assessment day if no response was observed. If there was no post-baseline CSC assessment, time to response was censored on study Day 1. Time to response was analyzed using Kaplan-Meier methods.

4. Time to Complete Response [From Day 1 until the end of study date or primary data cutoff date (13 September 2012), whichever occured first; median time on study was 1.8 months.]

   Time to complete response was defined as the time period from study Day 1 to the first time post-baseline corrected serum calcium (CSC) was ≤ 10.8 mg/dL (2.7 mmol/L). Participants were censored on the last CSC assessment day if no complete response was observed. If there was no post-baseline CSC assessment, time to complete response was censored on study Day 1. Time to complete response was analyzed using Kaplan-Meier methods.

5. Duration of Response [From Day 1 until the end of study date or primary data cutoff date (13 September 2012), whichever occured first; median time on study was 1.8 months.]

   Duration of response is defined as the number of days from the first day of corrected serum calcium ≤ 11.5 mg/dL (2.9 millimoles/L) to the last day of corrected serum calcium ≤ 11.5 mg/dL. Participants were censored on the last CSC assessment day if their CSC level never reached > 11.5 mg/dL after the first response. If a participant had no CSC assessment after the first response, duration of response was set to zero and censored. Duration of response was summarized for participants who achieved a response using the Kaplan-Meier method.

6. Duration of Complete Response [From Day 1 until the end of study date or primary data cutoff date (13 September 2012), whichever occured first; median time on study was 1.8 months.]

   Duration of complete response is defined as the number of days from the first day of of corrected serum calcium ≤ 10.8 mg/dL (2.7 millimoles/L) to the last day of corrected serum calcium ≤ 10.8 mg/dL. Participants were censored on the last CSC assessment day if their CSC level never reached > 10.8 mg/dL after the complete response. If a participant had no CSC assessment after the complete response, duration of complete response was set to zero and censored. Duration of complete response was summarized for participants who achieved a complete response using the Kaplan-Meier method.

7. Time to Relapse/Nonresponse of Hypercalcemia of Malignancy [From Day 1 until the end of study date or primary data cutoff date (13 September 2012), whichever occured first; median time on study was 1.8 months.]

   Time to relapse/nonresponse was defined as the number of days from study Day 1 until the last day of CSC ≤ 11.5 mg/dL for all particiipants with relapse after the first response. Participants were censored on the last CSC assessment day if their CSC level never reached > 11.5 mg/dL after first response. For participants who never achieved response, time to relapse/nonresponse was set to zero. Otherwise, if there was no post-baseline CSC assessment, time to relapse/nonresponse was censored on study Day 1. Time to relapse/nonresponse was estimated using the Kaplan-Meier method.

8. Change From Baseline in Corrected Serum Calcium [Baseline and Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Hypercalcemia of Malignancy (HCM) as defined as documented histologically or cytologically confirmed cancer and a corrected serum calcium (CSC) > 12.5 mg/dL (3.1 millimoles /L) at screening by local laboratory

• Last IV bisphosphonate treatment must be >/= to 7 days and </= to 30 days before the screening corrected serum calcium

• Adults (>/=18 years)

• Adequate organ function as defined by the following criteria:

• serum aspartate aminotransferase (AST) </= 5 x upper limit of normal (ULN)

• serum alanine aminotransferase (ALT) </= 5 x upper limit of normal

• serum total bilirubin </= 2 x upper limit of normal

Exclusion Criteria:

• Evidence of benign hyperparathyroidism, hyperthyroidism, adrenal insufficiency, vitamin D intoxication, milk alkali syndrome, sarcoidosis, or other granulomatous disease

• Receiving dialysis for renal failure

• Treatment with thiazides, calcitonin, mithramycin, or gallium nitrate within their window of expected therapeutic effect (as determined by the physician) prior to the date of the screening CSC

• Treatment with cinacalcet within 4 weeks prior to the date of the screening CSC

• Thirty days or less since receiving an investigational product (other than denosumab) or device (ie, does not have marketing authorization; thalidomide use is allowed) in another clinical study

• Known sensitivity to any of the products to be administered during the study (eg, mammalian derived products)

• Female subject is pregnant or breast feeding, or planning to become pregnant within 7 months after the end of treatment

• Female subject of childbearing potential is not willing to use 2 highly effective methods of contraception during treatment and for 7 months after the end of treatment

• Subject will not be available for follow-up assessment.

• Any organic or psychiatric disorder that, in the opinion of the investigator, might prevent the subject from completing the study or interfere with the interpretation of the study results

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Encinitas	California	United States	92024
2	Research Site	New Haven	Connecticut	United States	06520
3	Research Site	Salisbury	Maryland	United States	21801
4	Research Site	Dearborn	Michigan	United States	48124
5	Research Site	Detroit	Michigan	United States	48236
6	Research Site	Omaha	Nebraska	United States	68114
7	Research Site	Bronx	New York	United States	10467
8	Research Site	New York	New York	United States	10065
9	Research Site	Syracuse	New York	United States	13210
10	Research Site	Durham	North Carolina	United States	27710
11	Research Site	Goldsboro	North Carolina	United States	27534
12	Research Site	Houston	Texas	United States	77030
13	Research Site	Québec	Quebec	Canada	G1S 4L8
14	Research Site	Québec	Quebec	Canada	G1S 4L8
15	Research Site	Limoges Cedex		France	87042
16	Research Site	Montpellier Cedex 5		France	34298
17	Research Site	Nantes Cedex 1		France	44035
18	Research Site	Villejuif cedex		France	94805
19	Research Site	Bologna		Italy	40138
20	Research Site	Firenze		Italy	50139
21	Research Site	Milano		Italy	20162
22	Research Site	Padova		Italy	35128
23	Research Site	Roma		Italy	00128
24	Research Site	Warszawa		Poland	01-809

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00896454
• Other Study ID Numbers: 20070315
• First Posted: May 11, 2009
• Last Update Posted: Oct 17, 2018
• Last Verified: Sep 1, 2018

• Keywords provided by Amgen: hypercalcemia; calcium; bisphosphonates; denosumab; amgen; malignancy; 20070315; HMC; oncology; hematology
• Additional relevant MeSH terms: Lymphoma; Lung Neoplasms; Multiple Myeloma; Neoplasms; Kidney Neoplasms; Parathyroid Neoplasms; Paraneoplastic Syndromes; Endocrine Gland Neoplasms; Hypercalcemia; Denosumab

Study Results

Participant Flow

Recruitment Details	First patient was enrolled on 16 November 2009 and the last patient enrolled on 02 July 2012. Data are reported as of the primary analysis cut-off date of 13 September 2012.

Arm/Group Title	Denosumab
Arm/Group Description	Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Period Title: Overall Study
STARTED	33
COMPLETED	0
NOT COMPLETED	33

Baseline Characteristics

Arm/Group Title	Denosumab
Arm/Group Description	Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Overall Participants	33
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.3 (14.8)
Sex: Female, Male (Count of Participants)
Female	12 36.4%
Male	21 63.6%
Race/Ethnicity, Customized (participants) [Number]
White or Caucasian	23 69.7%
Black or African American	7 21.2%
Hispanic or Latino	1 3%
Asian	1 3%
Other	1 3%
Eastern Cooperative Oncology Group (ECOG) Performance Status (participants) [Number]
0	1 3%
1	7 21.2%
2	14 42.4%
3	8 24.2%
4	3 9.1%
Primary Tumor Type (participants) [Number]
Bladder	1 3%
Breast	6 18.2%
Head and neck	2 6.1%
Liver	1 3%
Neuroendocrine/carcinoid	4 12.1%
Non-hodgkin's	2 6.1%
Non-small cell lung cancer	3 9.1%
Ovarian	1 3%
Renal	3 9.1%
Small cell lung cancer	1 3%
Soft tissue sarcoma	1 3%
Unknown (primary tumor)	1 3%
Multiple myeloma	3 9.1%
Chronic lymphocytic leukemia	2 6.1%
IGG kappa multiple myeloma	1 3%
Myeloma	1 3%
Time from initial cancer diagnosis to enrollment (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	56.9 (68.8)
Presence of metastatic disease at enrollment (participants) [Number]
Yes	30 90.9%
No	3 9.1%
Presence of bone metastatic disease at enrollment (participants) [Number]
Yes	13 39.4%
No	20 60.6%
Baseline Hypercalcemia of Malignancy (HCM) Symptoms (participants) [Number]
Fatigue	9 27.3%
Anorexia	5 15.2%
Nausea	4 12.1%
Depressed level of consciousness	2 6.1%
Vomiting	2 6.1%
Dry mouth	1 3%
Constipation	4 12.1%
Lethargy	4 12.1%
Confusion	3 9.1%
Polyuria	2 6.1%
Abdominal pain	1 3%
Decreased mental acuity	1 3%
Dyspnea	1 3%
General weakness	1 3%
Insomnolence	1 3%
Light headedness (dizziness)	1 3%
Listlessness/muscle weakness	1 3%
Polyuro-polydipsic syndrome	1 3%
Psychomotor retardation	1 3%
Retching	1 3%
Urinary frequency	1 3%
Weight loss	1 3%
Calcium (corrected) (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	13.89 (1.27)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a Response Within 10 Days of First Dose of Denosumab
Description	Response is defined as corrected serum calcium (CSC) ≤ 11.5 mg/dL, within 10 days after the first dose of denosumab. For all CSC values, if albumin was < 4 g/dL, the following formula was used to calculate CSC: CSC = Total serum calcium [mg/dL] + (0.8 x (4 - serum albumin [g/dL]))
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

Response Analysis Subset including all participants who received at least 1 dose of denosumab and had a screening CSC (from local lab) > 12.5 mg/dL (3.1 mmol/L).

Arm/Group Title	Denosumab
Arm/Group Description	Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Measure Participants	33
Number (95% Confidence Interval) [percentage of participants]	63.6 192.7%

2. Secondary Outcome

Title	Percentage of Participants With a Response by Visit
Description	Response is defined as corrected serum calcium (CSC) ≤ 11.5 mg/dL, within 10 days after the first dose of denosumab. For all CSC values, if albumin was < 4 g/dL, the following formula was used to calculate CSC: CSC = Total serum calcium [mg/dL] + (0.8 x (4 - serum albumin [g/dL]))
Time Frame	Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57

Outcome Measure Data

Analysis Population Description

Response Analysis Subset

Arm/Group Title	Denosumab
Arm/Group Description	Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Measure Participants	33
By Day 2	9.1 27.6%
By Day 4	24.2 73.3%
By Day 8	48.5 147%
By Day 10	63.6 192.7%
By Day 15	63.6 192.7%
By Day 19	69.7 211.2%
By Day 23	69.7 211.2%
By Day 29	69.7 211.2%
By Day 36	69.7 211.2%
By Day 43	69.7 211.2%
By Day 50	69.7 211.2%
By Day 57	69.7 211.2%

3. Secondary Outcome

Title	Percentage of Participants With a Complete Response by Visit
Description	Response is defined as corrected serum calcium (CSC) ≤ 10.8 mg/dL (2.7 mmol/L). For all CSC values, if albumin was < 4 g/dL, the following formula was used to calculate CSC: CSC = Total serum calcium [mg/dL] + (0.8 x (4 - serum albumin [g/dL])).
Time Frame	Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57

Outcome Measure Data

Analysis Population Description

Response Analysis Subset

Arm/Group Title	Denosumab
Arm/Group Description	Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Measure Participants	33
By Day 2	3.0 9.1%
By Day 4	15.2 46.1%
By Day 8	27.3 82.7%
By Day 10	36.4 110.3%
By Day 15	45.5 137.9%
By Day 19	45.5 137.9%
By Day 23	51.5 156.1%
By Day 29	51.5 156.1%
By Day 36	60.6 183.6%
By Day 43	63.6 192.7%
By Day 50	63.6 192.7%
By Day 57	63.6 192.7%

4. Secondary Outcome

Title	Time to Response
Description	Time to Response was defined as the time period from study Day 1 to the first time post-baseline corrected serum calcium (CSC) ≤ 11.5 mg/dL. Participants were censored on the last CSC assessment day if no response was observed. If there was no post-baseline CSC assessment, time to response was censored on study Day 1. Time to response was analyzed using Kaplan-Meier methods.
Time Frame	From Day 1 until the end of study date or primary data cutoff date (13 September 2012), whichever occured first; median time on study was 1.8 months.

Outcome Measure Data

Analysis Population Description

Response Analysis Subset

Arm/Group Title	Denosumab
Arm/Group Description	Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Measure Participants	33
Median (95% Confidence Interval) [days]	9.0

5. Secondary Outcome

Title	Time to Complete Response
Description	Time to complete response was defined as the time period from study Day 1 to the first time post-baseline corrected serum calcium (CSC) was ≤ 10.8 mg/dL (2.7 mmol/L). Participants were censored on the last CSC assessment day if no complete response was observed. If there was no post-baseline CSC assessment, time to complete response was censored on study Day 1. Time to complete response was analyzed using Kaplan-Meier methods.
Time Frame	From Day 1 until the end of study date or primary data cutoff date (13 September 2012), whichever occured first; median time on study was 1.8 months.

Outcome Measure Data

Analysis Population Description

Response Analysis Subset

Arm/Group Title	Denosumab
Arm/Group Description	Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Measure Participants	33
Median (95% Confidence Interval) [days]	23.0

6. Secondary Outcome

Title	Duration of Response
Description	Duration of response is defined as the number of days from the first day of corrected serum calcium ≤ 11.5 mg/dL (2.9 millimoles/L) to the last day of corrected serum calcium ≤ 11.5 mg/dL. Participants were censored on the last CSC assessment day if their CSC level never reached > 11.5 mg/dL after the first response. If a participant had no CSC assessment after the first response, duration of response was set to zero and censored. Duration of response was summarized for participants who achieved a response using the Kaplan-Meier method.
Time Frame	From Day 1 until the end of study date or primary data cutoff date (13 September 2012), whichever occured first; median time on study was 1.8 months.

Outcome Measure Data

Analysis Population Description

Participants with a response in the Response Analysis Subset

Arm/Group Title	Denosumab
Arm/Group Description	Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Measure Participants	23
Median (95% Confidence Interval) [days]	104.0

7. Secondary Outcome

Title	Duration of Complete Response
Description	Duration of complete response is defined as the number of days from the first day of of corrected serum calcium ≤ 10.8 mg/dL (2.7 millimoles/L) to the last day of corrected serum calcium ≤ 10.8 mg/dL. Participants were censored on the last CSC assessment day if their CSC level never reached > 10.8 mg/dL after the complete response. If a participant had no CSC assessment after the complete response, duration of complete response was set to zero and censored. Duration of complete response was summarized for participants who achieved a complete response using the Kaplan-Meier method.
Time Frame	From Day 1 until the end of study date or primary data cutoff date (13 September 2012), whichever occured first; median time on study was 1.8 months.

Outcome Measure Data

Analysis Population Description

Participants with a complete response in the Response Analysis Subset

Arm/Group Title	Denosumab
Arm/Group Description	Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Measure Participants	21
Median (95% Confidence Interval) [days]	34.0

8. Secondary Outcome

Title	Time to Relapse/Nonresponse of Hypercalcemia of Malignancy
Description	Time to relapse/nonresponse was defined as the number of days from study Day 1 until the last day of CSC ≤ 11.5 mg/dL for all particiipants with relapse after the first response. Participants were censored on the last CSC assessment day if their CSC level never reached > 11.5 mg/dL after first response. For participants who never achieved response, time to relapse/nonresponse was set to zero. Otherwise, if there was no post-baseline CSC assessment, time to relapse/nonresponse was censored on study Day 1. Time to relapse/nonresponse was estimated using the Kaplan-Meier method.
Time Frame	From Day 1 until the end of study date or primary data cutoff date (13 September 2012), whichever occured first; median time on study was 1.8 months.

Outcome Measure Data

Analysis Population Description

Response Analysis Subset

Arm/Group Title	Denosumab
Arm/Group Description	Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Measure Participants	33
Median (95% Confidence Interval) [days]	19.0

9. Secondary Outcome

Title	Change From Baseline in Corrected Serum Calcium
Time Frame	Baseline and Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Subset included all participants who received at least 1 dose of denosumab. n = Number of participants who had non-missing data at Baseline and the time point of interest.

Arm/Group Title	Denosumab
Arm/Group Description	Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Measure Participants	33
Change from Baseline to Day 2 (n = 32)	-0.13
Change from Baseline to Day 4 (n = 32)	-0.25
Change form Baseline to Day 8 (n = 27)	-0.43
Change from Baseline to Day 10 (n = 28)	-0.54
Change from Baseline to Day 15 (n = 24)	-0.51
Change from Baseline to Day 19 (n = 22)	-0.64
Change from Baseline to Day 23 (n = 21)	-0.60
Change from Baseline to Day 29 (n = 22)	-0.53
Change from Baseline to Day 36 (n = 20)	-0.61
Change from Baseline to Day 43 (n = 19)	-0.75
Change from Baseline to Day 50 (n = 15)	-0.83
Change from Baseline to Day 57 (n = 17)	-0.73

Adverse Events

Time Frame	Median time on study was 1.8 months.
Adverse Event Reporting Description	Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Arm/Group Title	Denosumab 120 mg Q4W
Arm/Group Description	Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
All Cause Mortality
	Denosumab 120 mg Q4W
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Denosumab 120 mg Q4W
	Affected / at Risk (%)	# Events
Total	29/33 (87.9%)
Blood and lymphatic system disorders
Anaemia	1/33 (3%)
Pancytopenia	1/33 (3%)
Cardiac disorders
Cardiac arrest	1/33 (3%)
Tachycardia	2/33 (6.1%)
Endocrine disorders
Hypercalcaemia of malignancy	1/33 (3%)
Gastrointestinal disorders
Colitis	1/33 (3%)
Diarrhoea	2/33 (6.1%)
Nausea	1/33 (3%)
Oesophageal obstruction	1/33 (3%)
Vomiting	1/33 (3%)
General disorders
Pyrexia	1/33 (3%)
Hepatobiliary disorders
Hepatic failure	1/33 (3%)
Infections and infestations
Septic shock	1/33 (3%)
Urinary tract infection	1/33 (3%)
Investigations
Urine output decreased	1/33 (3%)
Metabolism and nutrition disorders
Dehydration	1/33 (3%)
Failure to thrive	1/33 (3%)
Hypercalcaemia	5/33 (15.2%)
Hypokalaemia	1/33 (3%)
Hyponatraemia	1/33 (3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer	1/33 (3%)
Breast cancer	1/33 (3%)
Breast cancer metastatic	1/33 (3%)
Chronic lymphocytic leukaemia	1/33 (3%)
Diffuse large B-cell lymphoma	1/33 (3%)
Gastrointestinal stromal tumour	1/33 (3%)
Head and neck cancer	2/33 (6.1%)
Hepatic neoplasm malignant	1/33 (3%)
Lung neoplasm malignant	2/33 (6.1%)
Multiple myeloma	2/33 (6.1%)
Non-small cell lung cancer	2/33 (6.1%)
Ovarian cancer	1/33 (3%)
Renal cell carcinoma	1/33 (3%)
Nervous system disorders
Lethargy	1/33 (3%)
Psychiatric disorders
Confusional state	1/33 (3%)
Mental status changes	1/33 (3%)
Renal and urinary disorders
Renal failure	1/33 (3%)
Renal failure acute	1/33 (3%)
Renal tubular necrosis	1/33 (3%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	1/33 (3%)
Dyspnoea	3/33 (9.1%)
Hypoxia	1/33 (3%)
Pleural effusion	1/33 (3%)
Pneumonia aspiration	1/33 (3%)
Respiratory distress	1/33 (3%)
Respiratory failure	1/33 (3%)
Vascular disorders
Hypotension	1/33 (3%)
Other (Not Including Serious) Adverse Events
	Denosumab 120 mg Q4W
	Affected / at Risk (%)	# Events
Total	26/33 (78.8%)
Blood and lymphatic system disorders
Anaemia	5/33 (15.2%)
Febrile neutropenia	2/33 (6.1%)
Neutropenia	2/33 (6.1%)
Thrombocytopenia	3/33 (9.1%)
Gastrointestinal disorders
Abdominal distension	3/33 (9.1%)
Abdominal pain	3/33 (9.1%)
Constipation	7/33 (21.2%)
Diarrhoea	7/33 (21.2%)
Dry mouth	2/33 (6.1%)
Nausea	10/33 (30.3%)
Vomiting	7/33 (21.2%)
General disorders
Asthenia	2/33 (6.1%)
Fatigue	6/33 (18.2%)
Oedema peripheral	8/33 (24.2%)
Pyrexia	4/33 (12.1%)
Infections and infestations
Pneumonia	3/33 (9.1%)
Injury, poisoning and procedural complications
Fall	2/33 (6.1%)
Investigations
Haemoglobin decreased	3/33 (9.1%)
Weight decreased	4/33 (12.1%)
Metabolism and nutrition disorders
Decreased appetite	7/33 (21.2%)
Fluid overload	5/33 (15.2%)
Hyperkalaemia	2/33 (6.1%)
Hypocalcaemia	3/33 (9.1%)
Hypophosphataemia	4/33 (12.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/33 (12.1%)
Back pain	4/33 (12.1%)
Musculoskeletal pain	2/33 (6.1%)
Myalgia	3/33 (9.1%)
Pain in extremity	2/33 (6.1%)
Nervous system disorders
Depressed level of consciousness	2/33 (6.1%)
Dizziness	2/33 (6.1%)
Headache	8/33 (24.2%)
Psychiatric disorders
Confusional state	3/33 (9.1%)
Insomnia	2/33 (6.1%)
Respiratory, thoracic and mediastinal disorders
Cough	6/33 (18.2%)
Dysphonia	2/33 (6.1%)
Dyspnoea	6/33 (18.2%)
Epistaxis	3/33 (9.1%)
Oropharyngeal pain	2/33 (6.1%)
Pleural effusion	4/33 (12.1%)
Pulmonary oedema	4/33 (12.1%)
Rhinorrhoea	2/33 (6.1%)
Skin and subcutaneous tissue disorders
Alopecia	3/33 (9.1%)
Palmar-plantar erythrodysaesthesia syndrome	2/33 (6.1%)
Rash	3/33 (9.1%)
Rash pruritic	2/33 (6.1%)
Vascular disorders
Hypotension	3/33 (9.1%)

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 multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.