Characteristics and Mechanism of Denosumab-treated Giant Cell Tumor of Bone (D-Gct)

Hebei Medical University Third Hospital

Status and phase: Unknown; Phase 3

Conditions: Giant Cell Tumor of Bone

Treatments: Drug: Denosumab

Study type: Interventional

Funder types: Other

Identifiers

NCT03259152

ZZ3592-2017

Details and patient eligibility

About

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.

Full 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).

Enrollment: 30 estimated patients

Sex: All

Ages: 14 to 60 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 2 patient groups

Pre-Denosumab GctB

Experimental group

Description:

Specimens obtained during biopsy

Treatment:

Drug: Denosumab

Post-Denosumab GctB

Experimental group

Description:

Specimen after administration of Denosumab

Treatment:

Drug: Denosumab