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Trial record 5 of 107 for:    Recruiting, Not yet recruiting, Available Studies | "Bone Neoplasms"

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

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ClinicalTrials.gov Identifier: NCT03259152
Recruitment Status : Recruiting
First Posted : August 23, 2017
Last Update Posted : August 24, 2017
Sponsor:
Information provided by (Responsible Party):
Hebei Medical University Third Hospital

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.

Condition or disease Intervention/treatment Phase
Giant Cell Tumor of Bone Drug: Denosumab Phase 3

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).

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Clinical, Pathologic Characteristics and Its Mechansim of Denosumab Treated Giant Cell Tumor of Bone
Actual Study Start Date : May 1, 2016
Estimated Primary Completion Date : May 1, 2019
Estimated Study Completion Date : May 1, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bone Cancer
Drug Information available for: Denosumab

Arm Intervention/treatment
Experimental: Pre-Denosumab GctB
Specimens obtained during biopsy
Drug: 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.
Other Name: Xgeva or Prolia

Experimental: Post-Denosumab GctB
Specimen after administration of Denosumab
Drug: 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.
Other Name: Xgeva or Prolia




Primary Outcome Measures :
  1. Molecular analysis (Immunohistochemistry for RANKL, RANK, OPG,Col-I, VEGF) [ Time Frame: 6 month ]

    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.


  2. Molecular analysis (RT-PCR for RANKL, RANK, OPG,Col-I, VEGF) [ Time Frame: 6 month ]
    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.


Secondary Outcome Measures :
  1. Visual Analog Score - Pain evaluation [ Time Frame: 6 months ]
    Visual analog scale [VAS] is a measure of pain intensity. It is a continuous scale comprised of a horizontal (called horizontal visual analogue scale) or,vertical called vertical visual analog scale usually 10 cm or 100 mm length [both the gradations are used]. It is anchored by two verbal descriptors, one for each symptom extreme. For pain intensity, the scale is most commonly anchored by "no pain" (score of 0) and "pain as bad as it could be" or "worst imaginable pain" (score of 100 [on 100-mm scale]

  2. Hematology test - Tartrate Resistant Acid Phosphatase [ Time Frame: 6 months ]
    Tartrate-resistant acid phosphatase, a bone resorption marker, is secreted from osteoclasts and this marker is reported to be high in patients with giant cell tumor of bone. We investigated the effects of denosumab and the usefulness of a tartrate-resistant acid phosphatase as a monitoring marker in the management of a refractory giant cell tumor of bone. Tartrate-resistant acid phosphatase secretion was measured in the patient's serum to monitor the response to denosumab, and a rapid normalization of the marker was observed after the first denosumab administration.

  3. Follow-up for recrudescence [ Time Frame: 6 month to 1 year ]

    Patients were followed up regularly for local or systemic tumor recurrence by X-ray, CT, MRI, ECT.

    The follow-up period was 3 months.


  4. Morphological change - HE (Hematoxylin-Eosin) staining [ Time Frame: 6 month ]
    For histological analysis of the adjacent intervertebral disc and fusion mass, the tissures of the Giant cell tumor of bone were fixed in 10% neutral buffered formalin, decalcified in 10% EDTA-2Na for 3 months, and then embedded in paraffin. They were subsequently cut into 5-mm sections with cationic slides. Slides of the tissures of the Giant cell tumor of bone were stained with H&E and captured by a microscope system (BX53; Olympus, Tokyo, Japan).

  5. Micro-vessel density or area by IHC - stained slides [ Time Frame: 6 month ]
    IHC - stained for VEGF images were used for microvessel density (MVD) and vascular bud relative area analysis. MVD was measured by counting the number of cartilage endplate vascular buds (an average of cephalic and caudal vascular buds). The ratio of vascular bud area to the total endplate area was measured for vascular bud relative area analysis using the grid method. MVD and vascular bud relative area analyses were repeated at least three times for enhanced accuracy

  6. Imaging changes by X-ray, CT, MRI, ECT. [ Time Frame: 6 month ]
    The patients' clinical information, images from radiographs, CT and MRI before and after Denosumab-treatment were recorded and analyzed. Tumor volume was measured on coronal, transverse, and sagital MRI or CT scansof the lesion; and maximum height, width, and depth were recorded; and the volume was calculated using the formula of an ellopsoid mass volume = [(π/6) × height × width × depth]. If CT or MRI were not available, tumor volume was measured on two-plane radiograghs.


Other Outcome Measures:
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 3 year ]
    The CTCAE v.4 criteria was used to evaluate late toxicity for all patients. Toxicity scores were recalculated for patients treated before publication of CTCAE v4.0 scale.



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Ages Eligible for Study:   14 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03259152


Contacts
Contact: Zhuang Zhou, Ph.D +86 18833130669 39094572@qq.com
Contact: Guochuan Zhang, M.D. +86 13932110889

Locations
China, Hebei
Zhuang Zhou Recruiting
Shijiazhuang, Hebei, China, 050000
Contact: Zhuang Zhou, Ph.D    +86 18833130669    39094572@qq.com   
Contact: Guochuan Zhang, M.D.    +86 13932110889      
Sponsors and Collaborators
Hebei Medical University Third Hospital
Investigators
Principal Investigator: Zhuang Zhou, Ph.D Hebei Medical University Third Hospital

Additional Information:
Publications:
Responsible Party: Hebei Medical University Third Hospital
ClinicalTrials.gov Identifier: NCT03259152     History of Changes
Other Study ID Numbers: ZZ3592-2017
First Posted: August 23, 2017    Key Record Dates
Last Update Posted: August 24, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: We have not yet planned to to make individual participant data (IPD) available to other researchers.

Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Hebei Medical University Third Hospital:
Giant cell tumor of bone
Denousmab
Pathologic
Clinical
Mechansim

Additional relevant MeSH terms:
Bone Neoplasms
Giant Cell Tumor of Bone
Giant Cell Tumors
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Bone Diseases
Musculoskeletal Diseases
Neoplasms, Bone Tissue
Denosumab
Bone Density Conservation Agents
Physiological Effects of Drugs