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

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

Official Title
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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

Conditions
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GCT, Giant Cell Tumor of Bone

Intervention / Treatment
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* Biological: Denosumab
* Dietary Supplement: Calcium/Vitamin D


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Denosumab<br>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<br>* Administered by subcutaneous injection<br>* Other names: Xgeva®;Dietary Supplement: Calcium/Vitamin D<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From enrollment until 25 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, and 81 | 
| 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. | 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 Denosumab Trough Concentrations | Serum concentrations of denosumab were measured by a validated conventional sandwich enzyme-linked immunosorbent assay (ELISA). | Blood samples were collected on Days 1 (baseline), 8, 15 and Weeks 5 (Day 29), 9, 13, 25, and 49. | 
| 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. | From the first dose of study drug until the data cut-off date of April 7 2008; a maximum of 18 months | 
| Number of Participants With Anti-Denosumab Antibodies | Validated immunoassays were used to test for the presence of anti-denosumab antibodies throughout the study. | From enrollment until the data cut-off date of April 7 2008; a maximum time of 18 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Giant Cell Tumor of Bone