Back to resultsStudy of Denosumab in the Treatment of Hypercalcemia of Malignancy in Subjects With Elevated Serum Calcium
Primary Purpose
Breast Cancer, Hypercalcemia of Malignancy, Colon Cancer
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
denosumab
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring hypercalcemia, calcium, bisphosphonates, denosumab, amgen, malignancy, 20070315, HMC, oncology, hematology
Eligibility Criteria
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
Sites / Locations
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Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
denosumab
Arm Description
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.
Outcomes
Primary Outcome Measures
Percentage of Participants With a Response Within 10 Days of First Dose of Denosumab
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
Percentage of Participants With a Response by Visit
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]))
Percentage of Participants With a Complete Response by Visit
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 to Response
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 to Complete Response
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.
Duration of Response
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.
Duration of Complete Response
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 to Relapse/Nonresponse of Hypercalcemia of Malignancy
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.
Change From Baseline in Corrected Serum Calcium
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00896454
Brief Title
Study of Denosumab in the Treatment of Hypercalcemia of Malignancy in Subjects With Elevated Serum Calcium
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
November 16, 2009 (Actual)
Primary Completion Date
September 13, 2012 (Actual)
Study Completion Date
August 21, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
hypercalcemia, calcium, bisphosphonates, denosumab, amgen, malignancy, 20070315, HMC, oncology, hematology
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
33 (Actual)
8. Arms, Groups, and Interventions
Arm Title
denosumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
denosumab
Intervention Description
120 mg subcutaneously (SC) every 4 weeks with a loading dose of 120 mg SC on study days 8 and 15.
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
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
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.
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.
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.
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.
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.
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Encinitas
State/Province
California
ZIP/Postal Code
92024
Country
United States
Facility Name
Research Site
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Research Site
City
Salisbury
State/Province
Maryland
ZIP/Postal Code
21801
Country
United States
Facility Name
Research Site
City
Dearborn
State/Province
Michigan
ZIP/Postal Code
48124
Country
United States
Facility Name
Research Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48236
Country
United States
Facility Name
Research Site
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
Research Site
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Research Site
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Research Site
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Research Site
City
Goldsboro
State/Province
North Carolina
ZIP/Postal Code
27534
Country
United States
Facility Name
Research Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Research Site
City
Québec
State/Province
Quebec
ZIP/Postal Code
G1S 4L8
Country
Canada
Facility Name
Research Site
City
Québec
State/Province
Quebec
ZIP/Postal Code
G1S 4L8
Country
Canada
Facility Name
Research Site
City
Limoges Cedex
ZIP/Postal Code
87042
Country
France
Facility Name
Research Site
City
Montpellier Cedex 5
ZIP/Postal Code
34298
Country
France
Facility Name
Research Site
City
Nantes Cedex 1
ZIP/Postal Code
44035
Country
France
Facility Name
Research Site
City
Villejuif cedex
ZIP/Postal Code
94805
Country
France
Facility Name
Research Site
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Research Site
City
Firenze
ZIP/Postal Code
50139
Country
Italy
Facility Name
Research Site
City
Milano
ZIP/Postal Code
20162
Country
Italy
Facility Name
Research Site
City
Padova
ZIP/Postal Code
35128
Country
Italy
Facility Name
Research Site
City
Roma
ZIP/Postal Code
00128
Country
Italy
Facility Name
Research Site
City
Warszawa
ZIP/Postal Code
01-809
Country
Poland
12. IPD Sharing Statement
Citations:
PubMed Identifier
23990665
Citation
Hu MI, Glezerman I, Leboulleux S, Insogna K, Gucalp R, Misiorowski W, Yu B, Ying W, Jain RK. Denosumab for patients with persistent or relapsed hypercalcemia of malignancy despite recent bisphosphonate treatment. J Natl Cancer Inst. 2013 Sep 18;105(18):1417-20. doi: 10.1093/jnci/djt225. Epub 2013 Aug 29.
Results Reference
derived
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Study of Denosumab in the Treatment of Hypercalcemia of Malignancy in Subjects With Elevated Serum Calcium
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