NCT00896454 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2018-10-17

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.

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Percentage of Participants With a Response Within 10 Days of First Dose of Denosumab

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outcome · POSTED

Percentage of Participants With a Response by Visit

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outcome · POSTED

Percentage of Participants With a Complete Response by Visit

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outcome · POSTED

Time to Response

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outcome · POSTED

Time to Complete Response

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outcome · POSTED

Duration of Response

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outcome · POSTED

Duration of Complete Response

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outcome · POSTED

Time to Relapse/Nonresponse of Hypercalcemia of Malignancy

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outcome · POSTED

Change From Baseline in Corrected Serum Calcium

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

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 Names
Drug: denosumab
label
denosumab
type
EXPERIMENTAL

interventions

arm Group Labels
denosumab
description
120 mg subcutaneously (SC) every 4 weeks with a loading dose of 120 mg SC on study days 8 and 15.
name
denosumab
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 33
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

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 \[g/dL\]))
measure
Percentage of Participants With a Response Within 10 Days of First Dose of Denosumab
time Frame
10 days

secondary Outcomes

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 \[g/dL\]))
measure
Percentage of Participants With a Response by Visit
time Frame
Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57
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 \[g/dL\])).
measure
Percentage of Participants With a Complete Response by Visit
time Frame
Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57
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.
measure
Time to Response
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.
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.
measure
Time to Complete Response
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.
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.
measure
Duration of Response
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.
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.
measure
Duration of Complete Response
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.
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.
measure
Time to Relapse/Nonresponse of Hypercalcemia of Malignancy
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.
measure
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

Full 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.

Source references

references

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.
pmid
23990665
type
DERIVED