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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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ClinicalTrials.gov Identifier: NCT00396279
Recruitment Status : Completed
First Posted : November 6, 2006
Results First Posted : March 5, 2014
Last Update Posted : February 19, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

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

Condition or disease Intervention/treatment Phase
GCT Giant Cell Tumor of Bone Biological: Denosumab Dietary Supplement: Calcium/Vitamin D Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 10, 2006
Actual Primary Completion Date : April 7, 2008
Actual Study Completion Date : February 1, 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bone Cancer
Drug Information available for: Denosumab

Arm Intervention/treatment
Experimental: Denosumab
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.
Biological: Denosumab
Administered by subcutaneous injection
Other Name: Xgeva®

Dietary Supplement: Calcium/Vitamin D



Primary Outcome Measures :
  1. Percentage of Participants With Giant Cell Tumor Response [ Time Frame: From enrollment until 25 weeks ]
    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 :
  1. Percent Change From Baseline in Urinary N-telopeptide Corrected for Urine Creatinine [ 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 ]
    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.

  2. Percent Change From Baseline in Serum C-terminus Peptide (of Type 1 Collagen) [ 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 ]
    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.

  3. Serum Denosumab Trough Concentrations [ Time Frame: Blood samples were collected on Days 1 (baseline), 8, 15 and Weeks 5 (Day 29), 9, 13, 25, and 49. ]
    Serum concentrations of denosumab were measured by a validated conventional sandwich enzyme-linked immunosorbent assay (ELISA).

  4. Number of Participants With Adverse Events (AEs) [ Time Frame: From the first dose of study drug until the data cut-off date of April 7 2008; a maximum of 18 months ]
    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.

  5. Number of Participants With Anti-Denosumab Antibodies [ Time Frame: From enrollment until the data cut-off date of April 7 2008; a maximum time of 18 months. ]
    Validated immunoassays were used to test for the presence of anti-denosumab antibodies throughout the study.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00396279


Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00396279     History of Changes
Other Study ID Numbers: 20040215
First Posted: November 6, 2006    Key Record Dates
Results First Posted: March 5, 2014
Last Update Posted: February 19, 2019
Last Verified: February 2019
Keywords provided by Amgen:
Giant Cell Tumor of Bone
Additional relevant MeSH terms:
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Giant Cell Tumors
Bone Neoplasms
Giant Cell Tumor of Bone
Neoplasms
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms by Site
Bone Diseases
Neoplasms, Bone Tissue
Bone Density Conservation Agents
Musculoskeletal Diseases
Vitamin D
Denosumab
Vitamins
Calcium
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Calcium-Regulating Hormones and Agents