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Safety and Efficacy Study of Denosumab in Patients With Recurrent or Unresectable Giant Cell Tumor of Bone

Primary Purpose

GCT, Giant Cell Tumor of Bone

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Denosumab
Calcium/Vitamin D
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for GCT focused on measuring Giant Cell Tumor of Bone

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Adults, 18 years and older
  • Histologically confirmed and measurable giant cell tumor (GCT)
  • Recurrent GCT confirmed by radiology or unresectable GCT
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

Exclusion Criteria:

  • Pateints for whom surgery to the affected limb/area is planned within 27 days after receiving 1st dose of denosumab
  • Radiation to affected region within 28 days before enrollment to study
  • Known diagnosis of osteosarcoma or brown tumor of bone
  • Known history of second malignancy within the past 5 years, except for basal cell carcinoma or cervical carcinoma in situ
  • Concurrent treatment with bisphosphonates, calcitonin, or interferon.

Other criteria also apply.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Denosumab

    Arm Description

    Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg doses on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason.

    Outcomes

    Primary Outcome Measures

    Percentage of Participants With Giant Cell Tumor Response
    A treatment response was defined for participants with tissue samples obtained and measured by histopathology as: • at least 90% elimination of giant cells relative to Baseline, or • complete elimination of giant cells in cases where giant cells represent < 5% of tumor cells. A response was defined for participants who have only radiographs (histopathology not available) as lack of progression of the target lesion at week 25 by radiographic measurements compared with Baseline. For participants with both a core biopsy and resected tissue obtained, the sample closest to week 25 was used in the analysis.

    Secondary Outcome Measures

    Percent Change From Baseline in Urinary N-telopeptide Corrected for Urine Creatinine
    Urinary N-telopeptide (of type 1 collagen) corrected for urine creatinine (uNTX/Cr) is a bone turnover marker used to measure the activity of denosumab. Percent change from Baseline in uNTX/Cr was measured over time.
    Percent Change From Baseline in Serum C-terminus Peptide (of Type 1 Collagen)
    Serum C-terminus peptide (of type 1 collagen; CTX1) is a bone turnover marker used to measure the activity of denosumab. Percent change from Baseline in CTX was measured over time.
    Serum Denosumab Trough Concentrations
    Serum concentrations of denosumab were measured by a validated conventional sandwich enzyme-linked immunosorbent assay (ELISA).
    Number of Participants With Adverse Events (AEs)
    An adverse event is defined as an undesirable medical occurrence (e.g., sign, symptom, or diagnosis) or worsening of a pre-existing medical condition. A serious adverse event (SAE) is defined by regulatory authorities as one that • is fatal • is life threatening (places the participant at immediate risk of death) • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • is a congenital anomaly/birth defect • other significant medical hazard. The severity of adverse events was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, version 3.0) based on the following general guideline: Grade 1: Mild AE Grade 2: Moderate AE Grade 3: Severe AE Grade 4: Life-threatening or disabling AE Grade 5: Death related to AE. AEs were assessed by the Investigator for relatedness to study drug.
    Number of Participants With Anti-Denosumab Antibodies
    Validated immunoassays were used to test for the presence of anti-denosumab antibodies throughout the study.

    Full Information

    First Posted
    November 2, 2006
    Last Updated
    November 4, 2022
    Sponsor
    Amgen
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00396279
    Brief Title
    Safety and Efficacy Study of Denosumab in Patients With Recurrent or Unresectable Giant Cell Tumor of Bone
    Official Title
    An Open-Label, Multi-Center, Phase 2 Safety and Efficacy Study of Denosumab (AMG 162) in Subjects With Recurrent or Unresectable Giant Cell Tumor (GCT) of Bone
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    November 2022
    Overall Recruitment Status
    Completed
    Study Start Date
    July 10, 2006 (Actual)
    Primary Completion Date
    April 7, 2008 (Actual)
    Study Completion Date
    February 1, 2011 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Amgen

    4. Oversight

    5. Study Description

    Brief Summary
    To determine how safe and effective denosumab is in treating patients with giant cell tumor of bone.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    GCT, Giant Cell Tumor of Bone
    Keywords
    Giant Cell Tumor of Bone

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    37 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Denosumab
    Arm Type
    Experimental
    Arm Description
    Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg doses on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason.
    Intervention Type
    Biological
    Intervention Name(s)
    Denosumab
    Other Intervention Name(s)
    Xgeva®
    Intervention Description
    Administered by subcutaneous injection
    Intervention Type
    Dietary Supplement
    Intervention Name(s)
    Calcium/Vitamin D
    Primary Outcome Measure Information:
    Title
    Percentage of Participants With Giant Cell Tumor Response
    Description
    A treatment response was defined for participants with tissue samples obtained and measured by histopathology as: • at least 90% elimination of giant cells relative to Baseline, or • complete elimination of giant cells in cases where giant cells represent < 5% of tumor cells. A response was defined for participants who have only radiographs (histopathology not available) as lack of progression of the target lesion at week 25 by radiographic measurements compared with Baseline. For participants with both a core biopsy and resected tissue obtained, the sample closest to week 25 was used in the analysis.
    Time Frame
    From enrollment until 25 weeks
    Secondary Outcome Measure Information:
    Title
    Percent Change From Baseline in Urinary N-telopeptide Corrected for Urine Creatinine
    Description
    Urinary N-telopeptide (of type 1 collagen) corrected for urine creatinine (uNTX/Cr) is a bone turnover marker used to measure the activity of denosumab. Percent change from Baseline in uNTX/Cr was measured over time.
    Time Frame
    Baseline and Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, and 81
    Title
    Percent Change From Baseline in Serum C-terminus Peptide (of Type 1 Collagen)
    Description
    Serum C-terminus peptide (of type 1 collagen; CTX1) is a bone turnover marker used to measure the activity of denosumab. Percent change from Baseline in CTX was measured over time.
    Time Frame
    Baseline and Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, and 81
    Title
    Serum Denosumab Trough Concentrations
    Description
    Serum concentrations of denosumab were measured by a validated conventional sandwich enzyme-linked immunosorbent assay (ELISA).
    Time Frame
    Blood samples were collected on Days 1 (baseline), 8, 15 and Weeks 5 (Day 29), 9, 13, 25, and 49.
    Title
    Number of Participants With Adverse Events (AEs)
    Description
    An adverse event is defined as an undesirable medical occurrence (e.g., sign, symptom, or diagnosis) or worsening of a pre-existing medical condition. A serious adverse event (SAE) is defined by regulatory authorities as one that • is fatal • is life threatening (places the participant at immediate risk of death) • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • is a congenital anomaly/birth defect • other significant medical hazard. The severity of adverse events was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, version 3.0) based on the following general guideline: Grade 1: Mild AE Grade 2: Moderate AE Grade 3: Severe AE Grade 4: Life-threatening or disabling AE Grade 5: Death related to AE. AEs were assessed by the Investigator for relatedness to study drug.
    Time Frame
    From the first dose of study drug until the data cut-off date of April 7 2008; a maximum of 18 months
    Title
    Number of Participants With Anti-Denosumab Antibodies
    Description
    Validated immunoassays were used to test for the presence of anti-denosumab antibodies throughout the study.
    Time Frame
    From enrollment until the data cut-off date of April 7 2008; a maximum time of 18 months.

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Adults, 18 years and older Histologically confirmed and measurable giant cell tumor (GCT) Recurrent GCT confirmed by radiology or unresectable GCT Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 Exclusion Criteria: Pateints for whom surgery to the affected limb/area is planned within 27 days after receiving 1st dose of denosumab Radiation to affected region within 28 days before enrollment to study Known diagnosis of osteosarcoma or brown tumor of bone Known history of second malignancy within the past 5 years, except for basal cell carcinoma or cervical carcinoma in situ Concurrent treatment with bisphosphonates, calcitonin, or interferon. Other criteria also apply.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    MD
    Organizational Affiliation
    Amgen
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    22711702
    Citation
    Branstetter DG, Nelson SD, Manivel JC, Blay JY, Chawla S, Thomas DM, Jun S, Jacobs I. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res. 2012 Aug 15;18(16):4415-24. doi: 10.1158/1078-0432.CCR-12-0578. Epub 2012 Jun 18.
    Results Reference
    background
    PubMed Identifier
    20149736
    Citation
    Thomas D, Henshaw R, Skubitz K, Chawla S, Staddon A, Blay JY, Roudier M, Smith J, Ye Z, Sohn W, Dansey R, Jun S. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 2010 Mar;11(3):275-80. doi: 10.1016/S1470-2045(10)70010-3. Epub 2010 Feb 10.
    Results Reference
    background
    PubMed Identifier
    30231890
    Citation
    Engellau J, Seeger L, Grimer R, Henshaw R, Gelderblom H, Choy E, Chawla S, Reichardt P, O'Neal M, Feng A, Jacobs I, Roberts ZJ, Braun A, Bach BA. Assessment of denosumab treatment effects and imaging response in patients with giant cell tumor of bone. World J Surg Oncol. 2018 Sep 19;16(1):191. doi: 10.1186/s12957-018-1478-3.
    Results Reference
    derived
    Links:
    URL
    http://www.amgentrials.com
    Description
    AmgenTrials clinical trials website

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    Safety and Efficacy Study of Denosumab in Patients With Recurrent or Unresectable Giant Cell Tumor of Bone

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