Study of Denosumab in Subjects With Giant Cell Tumor of Bone

September 9, 2022 updated by: Amgen

An Open-label, Multi-center, Phase 2 Study of Denosumab in Subjects With Giant Cell Tumor of Bone

To determine how safe denosumab is in treating subjects with giant cell tumor of bone (GCTB)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

To determine how safe denosumab is in treating subjects with GCTB

Study Type

Interventional

Enrollment (Actual)

535

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

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2250
        • Research Site
    • Queensland
      • Woolloongabba, Queensland, Australia, 4102
        • Research Site
    • Victoria
      • East Melbourne, Victoria, Australia, 3002
        • Research Site
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Research Site
  • Austria
      • Wien, Austria, 1090
        • Research Site
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X5
        • Research Site
    • Quebec
      • Montreal, Quebec, Canada, H4A 3J1
        • Research Site
  • France
      • Lyon cedex 8, France, 69373
        • Research Site
      • Marseille cedex 05, France, 13385
        • Research Site
      • Villejuif cedex, France, 94805
        • Research Site
  • Germany
      • Bad Saarow, Germany, 15526
        • Research Site
      • Stuttgart, Germany, 70174
        • Research Site
  • Italy
      • Bologna, Italy, 40136
        • Research Site
      • Milano, Italy, 20133
        • Research Site
  • Netherlands
      • Leiden, Netherlands, 2333 ZA
        • Research Site
  • Poland
      • Warszawa, Poland, 02-781
        • Research Site
      • Warszawa, Poland, 01-211
        • Research Site
  • Spain
    • Baleares
      • Palma de Mallorca, Baleares, Spain, 07010
        • Research Site
    • Cataluña
      • Barcelona, Cataluña, Spain, 08025
        • Research Site
    • Comunidad Valenciana
      • Valencia, Comunidad Valenciana, Spain, 46026
        • Research Site
  • Sweden
      • Lund, Sweden, 221 85
        • Research Site
  • United Kingdom
      • Birmingham, United Kingdom, B31 2AP
        • Research Site
  • United States
    • California
      • Santa Monica, California, United States, 90403
        • Research Site
      • Stanford, California, United States, 94305
        • Research Site
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Research Site
    • Florida
      • Gainesville, Florida, United States, 32607
        • Research Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Research Site
      • Boston, Massachusetts, United States, 02215
        • Research Site
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Research Site
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Research Site
    • New York
      • New York, New York, United States, 10003
        • Research Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19106
        • Research Site
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • 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

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • Pathologically confirmed GCTB within 1 year before study enrollment
  • Measurable evidence of active disease within 1 year before study enrollment
  • Subjects with surgically unsalvageable disease (eg, sacral, spinal GCTB, or multiple lesions including pulmonary metastases) OR subjects whose planned surgery includes joint resection, limb amputation, hemipelvectomy or surgical procedure resulting in severe morbidity
  • Karnofsky performance status equal or greater than 50% (ie, Eastern Cooperative Oncology Group status 0, 1, or 2)
  • Adults or skeletally mature adolescents (ie, radiographic evidence of at least 1 mature long bone [eg, humerus with closed growth epiphyseal plate]) equal or greater than 12 years of age
  • Skeletally mature adolescents must weigh at least 45 kg
  • Before any study-specific procedure is performed, the appropriate written informed consent must be obtained

Exclusion criteria:

  • Currently receiving other GCTB specific treatment (eg, radiation, chemotherapy, or embolization)
  • Concurrent bisphosphonate treatment
  • Known or suspected current diagnosis of underlying malignancy including high grade sarcoma, osteosarcoma, fibrosarcoma, malignant giant cell sarcoma
  • Known or suspected current diagnosis of non GCTB giant cell-rich tumors
  • Known or suspected current diagnosis of brown cell tumor of bone or Paget's disease
  • Known diagnosis of second malignancy within the past 5 years (subjects with definitively treated basal cell carcinoma and cervical carcinoma in situ are permitted)
  • Prior history or current evidence of osteonecrosis/osteomyelitis of the jaw
  • Active dental or jaw condition which requires oral surgery, including tooth extraction
  • Non-healed dental/oral surgery
  • Planned invasive dental procedure for the course of the study
  • Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s), or subject is receiving other investigational agent(s)
  • Subject has known sensitivity to any of the products to be administered during dosing
  • Unstable systemic disease including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, or myocardial infarction within 6 months before enrollment
  • Subject is pregnant or breast feeding, or planning to become pregnant within 5 months after the end of treatment
  • Female subject of child bearing potential is not willing to use two methods of highly effective contraception during treatment and for 5 months after the end of treatment
  • Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures

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
120 mg administered subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study days 8 and 15.
Drug: Denosumab
120 mg administered subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study days 8 and 15.
Other Names:
  • AMG 162, Immunoglobulin G2 human monoclonal antibody to RANK ligand

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: From first dose of study drug up to last study visit for treatment-emergent period (a maximum of approximately 111 months).
AE defined as any untoward medical occurrence in a clinical trial participant. Serious AE defined as AE that is fatal, life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or other significant medical hazard. Severity of AEs assessed according to Common Terminology Criteria for Adverse Events (CTCAE, v3.0) based on the general guideline: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening or disabling; Grade 5: Death related to AE. Investigator assessed AEs for relatedness to study drug. Results are presented for treatment-emergent events (TEAEs) and included all AEs occurring from first dose in initial treatment phase to end of initial treatment phase (or for participants entering retreatment, from first dose in initial treatment phase until end of retreatment phase).
From first dose of study drug up to last study visit for treatment-emergent period (a maximum of approximately 111 months).
Number of Participants Who Experienced the Maximum Toxicity Grade (CTCAE Grade ≥ 3) in the Indicated Clinical Chemistry Parameters
Time Frame: Baseline (day 1) up to last study visit for initial treatment phase (median duration approximately 30 months up to a maximum of approximately 109 months).
Serum samples for clinical chemistry were collected on study day 1 (baseline), day 15, week 5 and each study visit Q4W thereafter until last study visit for the on-study period (ie, until end of initial treatment phase). The parameters included albumin, calcium (albumin-adjusted), creatinine, magnesium and phosphate. Results are presented for number of participants who experienced the maximum toxicity grade for each of these clinical parameters. The maximum toxicity grade experienced by each participant was based on CTCAE, v3.0, and are summarized for Grade 3 and 4. Increases and decreases in relationship to the normal parameter ranges are indicated as 'Above' and 'Below' respectively.
Baseline (day 1) up to last study visit for initial treatment phase (median duration approximately 30 months up to a maximum of approximately 109 months).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Disease Progression or Recurrence During the On-Study Period for Cohort 1, Presented as Kaplan-Meier Estimates of Probability
Time Frame: From first dose of study drug up to the end of the initial treatment phase (median duration approximately 30 months up to a maximum of approximately 109 months).
Time to disease progression or recurrence during the on-study period was defined as the time interval (in days) from the date of first dose of study drug to the date of earliest Progressive Disease (PD) during the initial treatment phase. PD was defined as the response of progressive disease, locally recurrent disease or relapse as captured in the Disease Status page of the Case Report Form. If a participant had not had PD by the end of the initial treatment phase date, time to disease progression or recurrence were censored at her/his end of initial treatment phase date. Since median time to disease progression or recurrence for participants in cohort 1 was not reached, Kaplan-Meier estimates for the probability (expressed as a percentage) of participants in cohort 1 to have disease progression or recurrence at months 6, 12, 24, 36 and 60 are presented.
From first dose of study drug up to the end of the initial treatment phase (median duration approximately 30 months up to a maximum of approximately 109 months).
Percentage of Participants Without Any On-Study Surgery at Month 6 for Cohort 2
Time Frame: At month 6.
The percentage of participants without any surgery at month 6 was equivalent to the number of participants without any surgery by month 6 divided by the number of cohort 2 participants who had an opportunity to complete 6 months of treatment, expressed as a percentage.
At month 6.
Mean Serum Denosumab Trough Concentrations
Time Frame: Blood samples were collected at baseline (day 1), days 8 and 15 and weeks 5, 9, 13 and 25.
Blood samples for determination of serum denosumab concentration levels were obtained from participants included in the pharmacokinetic (PK) substudy at baseline (prior to administration of study drug on day 1) and at scheduled time points during the study up to week 25.
Blood samples were collected at baseline (day 1), days 8 and 15 and weeks 5, 9, 13 and 25.

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)

September 9, 2008

Primary Completion (Actual)

May 17, 2018

Study Completion (Actual)

May 17, 2018

Study Registration Dates

First Submitted

May 15, 2008

First Submitted That Met QC Criteria

May 15, 2008

First Posted (Estimate)

May 20, 2008

Study Record Updates

Last Update Posted (Actual)

September 22, 2022

Last Update Submitted That Met QC Criteria

September 9, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20062004

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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