Clinical trial NCT03259152: Characteristics and Mechanism of Denosumab-treated Giant Cell Tumor of Bone
Official title: Clinical, Pathologic Characteristics and Its Mechansim of Denosumab Treated Giant Cell Tumor of Bone
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Giant Cell Tumor of Bone
Keywords: Giant cell tumor of bone
Denousmab
Pathologic
Clinical
Mechansim
Lead sponsor: Hebei Medical University Third Hospital
Sponsor class: OTHER
First posted: 2017-08-23
Enrollment: 30
Sex: ALL
Minimum age (years): 14
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

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.

Primary outcomes:
measure: Molecular analysis (Immunohistochemistry for RANKL, RANK, OPG,Col-I, VEGF)
timeFrame: 6 month
measure: Molecular analysis (RT-PCR for RANKL, RANK, OPG,Col-I, VEGF)
timeFrame: 6 month
Secondary outcomes:
measure: Visual Analog Score - Pain evaluation
timeFrame: 6 months
measure: Hematology test - Tartrate Resistant Acid Phosphatase
timeFrame: 6 months
measure: Follow-up for recrudescence
timeFrame: 6 month to 1 year
measure: Morphological change - HE (Hematoxylin-Eosin) staining
timeFrame: 6 month
measure: Micro-vessel density or area by IHC - stained slides
timeFrame: 6 month
measure: Imaging changes by X-ray, CT, MRI, ECT.
timeFrame: 6 month
Other outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: 3 year
Locations:
city: Shijiazhuang
country: China
facility: Zhuang Zhou
state: Hebei
Study officials:
affiliation: Hebei Medical University Third Hospital
name: Zhuang Zhou, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.