Zoledronic Acid-loaded Bone Cement as a Local Adjuvant Therapy for Giant Cell Bone Tumor After Intralesional Curettage

Zoledronic Acid-loaded Bone Cement as a Local Adjuvant Therapy for Giant Cell Bone Tumor After Intralesional Curettage: a Prospective, Multicenter, Single Blinded, Randomized Control Trial.

The purpose of this study is to investigate whether zoledronic acid-loaded bone cement (4mg ZOL+ gentamicin PMMA ) as adjuvant method can decrease local recurrence in patients with giant cell bone tumor following intralesional curettage surgery. The hypothesis is that patients with local administration of zoledronic acid to the bone cement has lower relapse rate compared those with traditional bone cement(gentamicin PMMA ).

Study Overview

• Status: Recruiting
• Conditions: Giant Cell Tumor of Bone
• Intervention / Treatment: Procedure: 4mg ZOL loaded gentamicin PMMA; Procedure: gentamicin PMMA

Detailed Description

The purpose of the clinical study is to investigate whether the local delivery of zoledronic acid (4mg ZOL-loaded gentamicin PMMA bone cement) as a surgical adjuvant can decrease the local recurrence rate of giant cell tumor (GCT) of bone. The investigators will also evaluate whether patients with zoledronic acid as a surgical adjuvant improves secondary outcomes, including function (MSTS and TESS), surgery related complications (henderson's failure mode) and ZOL-related complications.

• Study Type: Interventional
• Enrollment (Anticipated): 153
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Meng Liu, MD; Phone Number: 13515711791; Email: liumeng80@163.com
• Study Contact Backup: Name: Keyi Wang, MS; Phone Number: 17398046579; Email: wky82630965@gmail.com

Study Locations

• China
  • Hangzhou, China, 311200
    • Recruiting
    • The Second Affiliated Hospital of Zhejiang University
    • Contact: Meng Liu; Phone Number: 13515711791; Email: liumeng80@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients with primary resectable GCT of bone
• lesion amenable to reconstruction (intralesional curettage) defined as having at least one intact column of bone after removal
• no previous systemic bisphosphonate or denosumab therapy
• with expected longer than 18 months of survival time
• sign the informed consent form

Exclusion Criteria:

• patients with recurrent GCT or extensive GCT which is impossible or inappropriate to use curettage surgery due to its "unresectable" nature.
• conduct unexpected surgery at other center
• the primary goal for surgery is revision
• patient conduct en-bloc/wide resection instead of curettage surgery
• patient can not conduct self-assessment during follow up
• difficulty in complete postoperative follow-up
• previous use of bisphosphonate/ZOL or denosumab drug
• patients have participated in similar research projects
• refused to sign informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zoledronic Acid loaded bone cement; 4mg zoledronic acid-loaded gentamicin bone cement (PMMA)	Procedure: 4mg ZOL loaded gentamicin PMMA; During surgery, 4mg ZOL will be mixed with gentamicin (1000mg) PMMA cement (40g) by surgeon under sterile conditions to prepare ZOL loaded bone cement, and then it will be filled into the bony defects of the patient where the lesion has been removed after intralesional curettage.
Active Comparator: conventional gentamicin bone cement; gentamicin bone cement (PMMA)	Procedure: gentamicin PMMA; During surgery, gentamicin (1000mg) PMMA (40g) was prepared by surgeon under sterile conditions and will be filled into the bony defects of the patient where the lesion has been removed after intralesional curettage.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
time to first local recurrence	Time to first local recurrence will be reported during postoperative 18-month follow up period	All patients will be followed for this endpoint until 18 months postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MSTS score	The Musculoskeletal Tumor Society (MSTS) scoring system is a disease-specific instrument to determine the physical and mental health for patients underwent limb-salvage surgery after tumor resection and is a validated and well-accepted functional scoring system used in orthopaedic oncology research	Doctors will be responsible in filling this questionnaire 3 months, 9 months, 12 months, 18 months postoperatively during patients' follow up
TESS score	The Toronto Extremity Salvage Score (TESS) is a physical disability measure developed specifically for patients undergoing surgery for extremity tumours and has been shown to have superior measurement properties compared with other commonly used sc	Patients will be asked to fill this survey 3 months, 9 months, 12 months, 18 months postoperatively
postoperative complication	Including wound healing problem, mechanical failure, infection and any tumor progression issues	Patients will be asked to report any complication 1 month, 3 months, 6 months, 9 months, 12 months, 18 months postoperatively during follow up
Potential ZOL-related complications	Patients will be followed for atypical bone fractures and avascular necrosis (AVN) of jaw, one of the most severe complication of ZOL	Patients will be followed to report any complication 1 month, 3 months, 6 months, 9 months, 12 months, 18 months postoperatively.

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2023
• Primary Completion (Anticipated): June 1, 2026
• Study Completion (Anticipated): December 1, 2026

Study Registration Dates

• First Submitted: October 23, 2022
• First Submitted That Met QC Criteria: October 25, 2022
• First Posted (Actual): October 27, 2022

Study Record Updates

• Last Update Posted (Actual): March 15, 2023
• Last Update Submitted That Met QC Criteria: March 13, 2023
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Zoledronic Acid, intralesional curettage
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Musculoskeletal Diseases; Bone Diseases; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Bone Neoplasms; Giant Cell Tumors; Giant Cell Tumor of Bone; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Anti-Infective Agents; Enzyme Inhibitors; Protective Agents; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Antimutagenic Agents; Gentamicins; Polymethyl Methacrylate
• Other Study ID Numbers: 2022_LM1020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No