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

NCT00396279 | Completed Phase 2 Results

• 1 other identifier: 20040215
• Study Type: interventional
• Target: 37
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

GCT; Giant Cell Tumor of Bone

Keywords

Giant Cell Tumor of Bone

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Percent Change From Baseline in Urinary N-telopeptide Corrected for Urine Creatinine

  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)

  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

  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)

  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

  From enrollment until the data cut-off date of April 7 2008; a maximum time of 18 months.

Study Arms (1)

Denosumab

EXPERIMENTAL

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; Dietary Supplement: Calcium/Vitamin D

Interventions

Denosumab BIOLOGICAL

Administered by subcutaneous injection

Also known as: Xgeva®

Denosumab

Calcium/Vitamin D DIETARY_SUPPLEMENT

Denosumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Related Publications (3)

• 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.

  PMID: 22711702 BACKGROUND

• 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.

  PMID: 20149736 BACKGROUND

• 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.

  PMID: 30231890 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Giant Cell Tumor of Bone

Interventions

Denosumab; Calcium; Vitamin D

Condition Hierarchy (Ancestors)

Giant Cell Tumors; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Bone Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Metals, Alkaline Earth; Elements; Inorganic Chemicals; Metals; Blood Coagulation Factors; Biological Factors; Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2006
• First Posted: November 6, 2006
• Study Start: July 10, 2006
• Primary Completion: April 7, 2008
• Study Completion: February 1, 2011
• Last Updated: November 8, 2022
• Results First Posted: March 5, 2014

Record last verified: 2022-11