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

September 20, 2018 updated by: Amgen

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

33

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Québec, Quebec, Canada, G1S 4L8
        • Research Site
      • Québec, Quebec, Canada, G1S 4L8
        • Research Site
  • France
      • Limoges Cedex, France, 87042
        • Research Site
      • Montpellier Cedex 5, France, 34298
        • Research Site
      • Nantes Cedex 1, France, 44035
        • Research Site
      • Villejuif cedex, France, 94805
        • Research Site
  • Italy
      • Bologna, Italy, 40138
        • Research Site
      • Firenze, Italy, 50139
        • Research Site
      • Milano, Italy, 20162
        • Research Site
      • Padova, Italy, 35128
        • Research Site
      • Roma, Italy, 00128
        • Research Site
  • Poland
      • Warszawa, Poland, 01-809
        • Research Site
  • United States
    • California
      • Encinitas, California, United States, 92024
        • Research Site
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Research Site
    • Maryland
      • Salisbury, Maryland, United States, 21801
        • Research Site
    • Michigan
      • Dearborn, Michigan, United States, 48124
        • Research Site
      • Detroit, Michigan, United States, 48236
        • Research Site
    • Nebraska
      • Omaha, Nebraska, United States, 68114
        • Research Site
    • New York
      • Bronx, New York, United States, 10467
        • Research Site
      • New York, New York, United States, 10065
        • Research Site
      • Syracuse, New York, United States, 13210
        • Research Site
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Research Site
      • Goldsboro, North Carolina, United States, 27534
        • Research Site
    • Texas
      • Houston, Texas, United States, 77030
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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]))
10 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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]))
Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57
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])).
Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57
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.
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
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.
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
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.
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
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.
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 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.
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.
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
Baseline and Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Amgen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 16, 2009

Primary Completion (Actual)

September 13, 2012

Study Completion (Actual)

August 21, 2013

Study Registration Dates

First Submitted

May 7, 2009

First Submitted That Met QC Criteria

May 7, 2009

First Posted (Estimate)

May 11, 2009

Study Record Updates

Last Update Posted (Actual)

October 17, 2018

Last Update Submitted That Met QC Criteria

September 20, 2018

Last Verified

September 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20070315

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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