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

Giant Cell Tumor of Bone Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00396279
• Other study ID #: 20040215
• Status: Completed
• Phase: Phase 2
• Start date: July 10, 2006
• Est. completion date: February 1, 2011

Study information

• Verified date: November 2022
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: February 1, 2011
• Est. primary completion date: April 7, 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bone Neoplasms
• GCT
• Giant Cell Tumor of Bone
• Giant Cell Tumors

Intervention

Biological:
• Denosumab
Administered by subcutaneous injection

Dietary Supplement:
• Calcium/Vitamin D

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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.
Secondary	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
Secondary	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.

External Links

•   AmgenTrials clinical trials website