Characteristics and Mechanism of Denosumab-treated Giant Cell Tumor of Bone

NCT ID: NCT03259152

Last Updated: 2017-08-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-01
• Study Completion Date: 2019-05-01

Brief Summary

Giant cell tumor of bone (GCTb) is a primary, osteolytic, benign tumor of the bone. Surgery is the commonly used treatment. Discovery of RANKL and its human monoclonal antibody, denosumab, led to use of denosumab for treatment of GCT. The aim of this study was to evaluate clinical and pathological results of treatment of relapsed or refractoriness GCT with denosumab and to assess adverse effect profile and recurrence rate.

Detailed Description

Giant cell tumor of bone (GCTb) is an aggressive, benign bone tumor. GCTb, which was first defined by Cooper and Travers, can produce pulmonary metastasis, albeit rarely (1-6%). GCTb constitutes 5% of primary bone tumors and 20% of benign bone tumors. Histologically, the tumour consists of a proliferation of mononuclear cells, accompanied by a population of non-neoplastic osteoclast-like giant cells and mononuclear osteoclast precursors. Currently, it is thought that proliferating neoplastic cells produce a number of cytokines and mediators, including the receptor activator of nuclear factor κ-B-ligand (RANK-RANKL) system, that recruit osteoclast precursors and induce their maturation into multinucleated osteoclast. The standard management of GCTb is based on surgery with several local adjuvant treatments like methacrylate cement, phenol or cryotherapy to reduce the risk of recurrence, while bisphosphonates are used in some cases to decrease bone resorption and for pain relief in inoperable tumours or metastatic disease. In the last 5 years the use of denosumab, a fully human monoclonal antibody already licensed for postmenopausal osteoporosis and prevention of skeletal related events in bone metastases from solid tumours, has been introduced in the treatment strategy of GCTb. In this study we examined the clinical, radiological, histological and underlying mechanism features of a series of GCTb, before and after denosumab administration, comparing baseline and resection specimens. Moreover, we examined the safety of the drug and on the angiogenesis through the determination of microvascular density (MVD).

Conditions

Giant Cell Tumor of Bone

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Pre-Denosumab GctB

Specimens obtained during biopsy

Group Type: EXPERIMENTAL

Denosumab

Intervention Type: DRUG

Denosumab (trade names Prolia and Xgeva) is a human monoclonal antibody for the treatment of osteoporosis, treatment-induced bone loss, metastases to bone, and giant cell tumor of bone.Denosumab is a RANKL inhibitor, which works by preventing the development of osteoclasts which are cells that break down bone.

Post-Denosumab GctB

Specimen after administration of Denosumab

Group Type: EXPERIMENTAL

Denosumab

Intervention Type: DRUG

Denosumab (trade names Prolia and Xgeva) is a human monoclonal antibody for the treatment of osteoporosis, treatment-induced bone loss, metastases to bone, and giant cell tumor of bone.Denosumab is a RANKL inhibitor, which works by preventing the development of osteoclasts which are cells that break down bone.

Interventions

Denosumab

Denosumab (trade names Prolia and Xgeva) is a human monoclonal antibody for the treatment of osteoporosis, treatment-induced bone loss, metastases to bone, and giant cell tumor of bone.Denosumab is a RANKL inhibitor, which works by preventing the development of osteoclasts which are cells that break down bone.

Intervention Type: DRUG

Other Intervention Names

Xgeva or Prolia

Eligibility Criteria

Inclusion Criteria

• Giant cell tumor of bone patients confirmed by clinical, medical imaging and Pathology.

Exclusion Criteria

• (1) less than 14 patients; 2) pregnant patients; 3) A patient who receives other medications during treatment.

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hebei Medical University Third Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zhuang Zhou, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Hebei Medical University Third Hospital

Locations

Zhuang Zhou

Shijiazhuang, Hebei, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhuang Zhou, Ph.D

Role: CONTACT

39094572@qq.com

+86 18833130669

Guochuan Zhang, M.D.

Role: CONTACT

+86 13932110889

Facility Contacts

Zhuang Zhou, Ph.D

Role: primary

39094572@qq.com

+86 18833130669

Guochuan Zhang, M.D.

Role: backup

+86 13932110889

References

Girolami I, Mancini I, Simoni A, Baldi GG, Simi L, Campanacci D, Beltrami G, Scoccianti G, D'Arienzo A, Capanna R, Franchi A. Denosumab treated giant cell tumour of bone: a morphological, immunohistochemical and molecular analysis of a series. J Clin Pathol. 2016 Mar;69(3):240-7. doi: 10.1136/jclinpath-2015-203248. Epub 2015 Sep 3.

Reference Type: BACKGROUND

PMID: 26338802 (View on PubMed)

Deveci MA, Paydas S, Gonlusen G, Ozkan C, Bicer OS, Tekin M. Clinical and pathological results of denosumab treatment for giant cell tumors of bone: Prospective study of 14 cases. Acta Orthop Traumatol Turc. 2017 Jan;51(1):1-6. doi: 10.1016/j.aott.2016.03.004. Epub 2016 Oct 24.

Reference Type: BACKGROUND

PMID: 27784623 (View on PubMed)

Rutkowski P, Ferrari S, Grimer RJ, Stalley PD, Dijkstra SP, Pienkowski A, Vaz G, Wunder JS, Seeger LL, Feng A, Roberts ZJ, Bach BA. Surgical downstaging in an open-label phase II trial of denosumab in patients with giant cell tumor of bone. Ann Surg Oncol. 2015 Sep;22(9):2860-8. doi: 10.1245/s10434-015-4634-9. Epub 2015 Jun 2.

Reference Type: BACKGROUND

PMID: 26033180 (View on PubMed)

Related Links

https://en.wikipedia.org/wiki/Denosumab

Description of Denosumab

Other Identifiers

ZZ3592-2017

Identifier Type: -

Identifier Source: org_study_id