NCT03259152

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
30

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started May 2016

Typical duration for phase_3

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2016

Completed
1.3 years until next milestone

First Submitted

Initial submission to the registry

August 17, 2017

Completed
6 days until next milestone

First Posted

Study publicly available on registry

August 23, 2017

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2019

Completed
Last Updated

August 24, 2017

Status Verified

May 1, 2017

Enrollment Period

3 years

First QC Date

August 17, 2017

Last Update Submit

August 23, 2017

Conditions

Giant Cell Tumor of Bone

Keywords

Giant cell tumor of boneDenousmabPathologicClinicalMechansim

Outcome Measures

Primary Outcomes (2)

  • Molecular analysis (Immunohistochemistry for RANKL, RANK, OPG,Col-I, VEGF)

    For collagen RANKL (Receptor Activator for Nuclear Factor-κ B Ligand), RANK (Receptor Activator for Nuclear Factor-κ B), OPG (Osteoprotegerin), Col-I (type I Collagen), VEGF (Vascular Endothelial Growth Factor) immunohistochemistry, sections were deparaffinized, rehydrated, and immunostained with a SA1024 SABC-POD kit and Kit-0017 DAB detection kit. Briefly, antigen retrieval was performed, and endogenous peroxidases were then inactivated prior to incubation with primary antibodies overnight at 4°C. This was followed by incubation with a biotinylated secondary antibody and a streptavidin-biotin complex peroxidase solution. Diaminobenzidine (DAB) chromogen was applied and counterstained with hematoxylin for antibody detection. Images were captured by a microscope system at 400-magnification. The integrated optical density values of each factor were semiquantitatively analyzed using Imaging Pro Plus 6.0 software.

    6 month

  • Molecular analysis (RT-PCR for RANKL, RANK, OPG,Col-I, VEGF)

    Tissures mRNA was extracted using TRIzol reagent (Invitrogen, Carlsbad, CA). The RNA concentration and quality were assessed using a Quawell Q5000 spectrophotometer (Quawell, San Jose, CA). Reverse transcription PCR was performed using a Gene Amp 7700 Sequence Detection System (Applied Biosystems, Foster City, CA) and custom-designed, validated primers for Col1α1, Col2α1, Aggrecan, MMP-13, and ADAMTS-4. GAPDH was used as the housekeeping gene. Relative gene expression changes were reported using the 2(-Delta Delta C(T)) method as previously described. The experiment was repeated in triplicate to ensure accuracy.

    6 month

Secondary Outcomes (6)

  • Visual Analog Score - Pain evaluation

    6 months

  • Hematology test - Tartrate Resistant Acid Phosphatase

    6 months

  • Follow-up for recrudescence

    6 month to 1 year

  • Morphological change - HE (Hematoxylin-Eosin) staining

    6 month

  • Micro-vessel density or area by IHC - stained slides

    6 month

  • +1 more secondary outcomes

Other Outcomes (1)

  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    3 year

Study Arms (2)

Pre-Denosumab GctB

EXPERIMENTAL

Specimens obtained during biopsy

Drug: Denosumab

Post-Denosumab GctB

EXPERIMENTAL

Specimen after administration of Denosumab

Drug: Denosumab

Interventions

DenosumabDRUG

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.

Also known as: Xgeva or Prolia
Post-Denosumab GctBPre-Denosumab GctB

Eligibility Criteria

Age14 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Zhuang Zhou

Shijiazhuang, Hebei, 050000, China

RECRUITING

Related Publications (3)

  • 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.

    PMID: 26338802BACKGROUND

  • 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.

    PMID: 27784623BACKGROUND

  • 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.

    PMID: 26033180BACKGROUND

Related Links

MeSH Terms

Conditions

Giant Cell Tumor of Bone

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Giant Cell TumorsNeoplasms, Connective TissueNeoplasms, Connective and Soft TissueNeoplasms by Histologic TypeNeoplasmsNeoplasms, Bone Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Zhuang Zhou, Ph.D

    Hebei Medical University Third Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhuang Zhou, Ph.D

CONTACT

+86 1883313066939094572@qq.com

Guochuan Zhang, M.D.

CONTACT

+86 13932110889

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 17, 2017

First Posted

August 23, 2017

Study Start

May 1, 2016

Primary Completion

May 1, 2019

Study Completion

May 1, 2019

Last Updated

August 24, 2017

Record last verified: 2017-05

Data Sharing

IPD Sharing
Will not share

We have not yet planned to to make individual participant data (IPD) available to other researchers.

Locations

CN(1)