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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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 Treat

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.

Detailed Summary:
Sponsor: Amgen

Current Primary Outcome: Percentage of Participants With a Response Within 10 Days of First Dose of Denosumab [ Time Frame: 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]))


Original Primary Outcome: Proportion of subjects with a response, defined as corrected serum calcium </= 11.5 mg/dL (2.9 millimoles/L) within 10 days after the first dose of denosumab. [ Time Frame: 10 days ]

Current Secondary Outcome:

  • Percentage of Participants With a Response by Visit [ Time Frame: 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]))
  • 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 ]
    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 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. ]

    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 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. ]
    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 [ 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. ]
    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 [ 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. ]
    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 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. ]
    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 [ Time Frame: Baseline and Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57 ]


Original Secondary Outcome:

  • Porportion of subjects with a response (ie, corrected serum calcium </= 11.5 mg/dL (2.9 millimoles/L) by visit [ Time Frame: 33 months ]
  • Proportion of subjects with a complete response (CR) (ie, corrected serum calcium </= 10.8 mg/dL (2.7 millimoles/L) by visit [ Time Frame: 33 months ]
  • Time to Response [ Time Frame: 33 months ]
  • Time to complete response [ Time Frame: 33 months ]
  • Duration of response 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 (2.9 millimoles/L) [ Time Frame: 33 months ]
  • Duration of complete response 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 (2.7 millimoles/L) [ Time Frame: 33 months ]
  • Time to relapse of hypercalcemia of malignacy defined as the number of days from the day of the first dose of denosumab until the last day of corrected serum calcium </= 11.5 mg/dL (2.9 millimoles/L) [ Time Frame: 33 months ]
  • Changes in corrected serum calcium from baseline [ Time Frame: 33 months ]


Information By: Amgen

Dates:
Date Received: May 7, 2009
Date Started: November 2009
Date Completion:
Last Updated: February 18, 2016
Last Verified: February 2016