Safety and Efficacy of Post-operative Denosumab Strategy for Giant Cell Tumor of Bone Treatment in China

Giant Cell Tumor of Bone Clinical Trial

Official title:

Safety and Efficacy of Post-operative Denosumab Strategy for Giant Cell Tumor of Bone Treatment in China：Correlation Between Recurrence and Drug Withdrawl

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03358212
• Other study ID #: GCTB-China
• Status: Not yet recruiting
• Phase: N/A
• First received: November 26, 2017
• Last updated: November 29, 2017
• Start date: March 1, 2018
• Est. completion date: June 1, 2021

Study information

• Verified date: November 2017
• Source: Peking University People's Hospital
• Contact: Chen Zhongyan, MD
• Phone: +8615201285835
• Email: harrypotterchen[@]126.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

This prospective observational study is going to figure out the safety and efficacy of denosumab as an post-operative strategy.All the patients enrolled will take denosumab according to the protocols.We focus on the recurrence rate after the drug withdrawl and possibility of malignant transformation.

Description:

This prospective observational study is going to figure out the safety and efficacy of denosumab as an post-operative strategy.

This study only included patients who meet all the following criteria: (1) With treatment-naïve sacral giant-cell tumor (GCT) firstly treated in our center (for referral patients, only those with definite diagnosis were included); (2) Being diagnosed with classic giant-cell tumor of bone (GCTB) by puncture pathology prior to treatment (for referral patients, definite diagnosis shall be made by the Pathology Department in our center through pathology consultation on tissue sections); (3) previously denosumab-naïve.

Data collection:The following data of patients included in this study were collected: (1) basic information: age, gender; (2) pathological data: puncture pathological diagnosis, and postoperative pathological findings; (3) the imaging findings (including X-ray, CT, Magnetic resonance(MR), Positron Emission Tomography-Computed Tomography(PET-CT)) and functional assessment of patients in the neoadjuvant denosumab group before and after the use of denosumab; (4) intraoperative blood loss, and duration of operation; (5) imaging findings in postoperative follow-up re-examination and outcome.

functional assessment: For sacral giant cell tumor:The Motor Urination defecation(MUD) scoring system published on Spine by our center in 2016 , which include three domains (motor function and sensation of lower limbs [M], urination and uriesthesia [U], and Defecation and rectal sensation [D]) with three items in each domain (each item can be scored by 0, 1, 2 or 3, and the maximum score is 27), was applied in the functional assessment of sacral nerves.

For GCT occurs in Limbs ,we use Musculoskeletal Tumor Society (MSTS) 93 to record the function.

All the patients enrolled will take denosumab according to the protocols:denosumab 120mg was administrated to patients by subcutaneous injection every four weeks, with loading doses on Day 8 and Day 15 of the first cycle,them take it monthly till 1 year after the surgery.We focus on the recurrence rate after the drug withdrawl and possibility of malignant transformation.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: June 1, 2021
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 50 Years

Eligibility

Inclusion Criteria:

(1) With treatment-naïve sacral GCT firstly treated in our center (for referral patients, only those with definite diagnosis were included); (2)single center lesion (3) Being diagnosed with classic GCTB by puncture pathology prior to treatment (for referral patients, definite diagnosis shall be made by the Pathology Department in our center through pathology consultation on tissue sections); (4) previously denosumab-naïve.

Exclusion Criteria:(1)primary malignant giant cell tumor of bone(2)radiation therapy in history(3)lung metastasis at first diagnosis

Related Conditions & MeSH terms

• Bone Neoplasms
• Giant Cell Tumor of Bone
• Giant Cell Tumors

Intervention

Drug:
• Denosumab
Denosumab 120mg was administrated to patients by subcutaneous injection every four weeks, with loading doses on Day 8 and Day 15 of the first cycle.Patients were instructed to take calcium supplements orally every day and avoid any oral operation during treatment

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Peking University People's Hospital

References & Publications (6)

Branstetter DG, Nelson SD, Manivel JC, Blay JY, Chawla S, Thomas DM, Jun S, Jacobs I. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res. 2012 Aug 15;18(16):4415-24. doi: 10.1158/1078-0432.CCR-12-0578. Epub 2012 Jun 18. — View Citation

Chawla S, Henshaw R, Seeger L, Choy E, Blay JY, Ferrari S, Kroep J, Grimer R, Reichardt P, Rutkowski P, Schuetze S, Skubitz K, Staddon A, Thomas D, Qian Y, Jacobs I. Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study. Lancet Oncol. 2013 Aug;14(9):901-8. doi: 10.1016/S1470-2045(13)70277-8. Epub 2013 Jul 16. — View Citation

Mak IW, Evaniew N, Popovic S, Tozer R, Ghert M. A Translational Study of the Neoplastic Cells of Giant Cell Tumor of Bone Following Neoadjuvant Denosumab. J Bone Joint Surg Am. 2014 Aug 6;96(15):e127. — View 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. — View Citation

Ueda T, Morioka H, Nishida Y, Kakunaga S, Tsuchiya H, Matsumoto Y, Asami Y, Inoue T, Yoneda T. Objective tumor response to denosumab in patients with giant cell tumor of bone: a multicenter phase II trial. Ann Oncol. 2015 Oct;26(10):2149-54. doi: 10.1093/annonc/mdv307. Epub 2015 Jul 23. — View Citation

Wojcik J, Rosenberg AE, Bredella MA, Choy E, Hornicek FJ, Nielsen GP, Deshpande V. Denosumab-treated Giant Cell Tumor of Bone Exhibits Morphologic Overlap With Malignant Giant Cell Tumor of Bone. Am J Surg Pathol. 2016 Jan;40(1):72-80. doi: 10.1097/PAS.0000000000000506. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	recurrence without metastasis	CT or MR proof that the tumor relapse in the primary site by at least two radiologist	up to 2 years
Secondary	metastasis without recurrence	confirmed via lung CT scan by at least two radiologist	up to 2 years
Secondary	death from other disease	patient die from another disease but must not from giant cell tumor	up to 2 years
Secondary	death from giant cell tumor	patient die from the tumor itself	up to 2 years