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

Phase 2CompletedNCT00396279

Amgen37 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

GCT Giant Cell Tumor of Bone

Interventions

DenosumabBIOLOGICAL

Administered by subcutaneous injection

Calcium/Vitamin DDIETARY_SUPPLEMENT

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: From enrollment until 25 weeks

Secondary Outcomes

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.

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

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.

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 Denosumab Trough Concentrations

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.

Number of Participants With Adverse Events (AEs)

Data from ClinicalTrials.gov

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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.