Local Bisphosphonate Effect on Recurrence Rate in Extremity Giant Cell Tumor of Bone

Local Bisphosphonate Effect on Recurrence Rate in Extremity Giant Cell Tumor of Bone: A Prospective Randomized Controlled Trial

The purpose of the clinical study is to investigate whether the local delivery of bisphosphonate as a surgical adjuvant can decrease the chance of a giant cell tumor of bone coming back to the same location. The hypothesis is that the local administration of bisphosphonate will decrease the rate of the tumor returning compared to traditional aggressive surgical removal of the tumor.

Study Overview

• Status: Recruiting
• Conditions: Giant Cell Tumor of Bone
• Intervention / Treatment: Drug: Zoledronic Acid

Detailed Description

The purpose of the clinical study is to investigate whether the local delivery of bisphosphonate (BP-loaded PMMA bone cement) as a surgical adjuvant can decrease the local recurrence rate of giant cell tumor (GCT) of bone. The investigators will evaluate whether bisphosphonate as a surgical adjuvant improves secondary outcomes, such as pain, function, fever, or wound complications. The hypothesis is that the local administration of bisphosphonate will decrease the recurrence rate of GCT compared to traditional aggressive intralesional curettage.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Allison Gruender, RN; Phone Number: 314-617-3406; Email: allison.gruender@health.slu.edu
• Study Contact Backup: Name: Marsha Steffen, RN; Phone Number: 314-617-3410; Email: marsha.steffen@health.slu.edu

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H3G 1A4
      • Recruiting
      • McGill University Health Centre
      • Contact: Nadine Zablith; Email: nadine.zablith@muhc.mcgill.ca
      • Principal Investigator: Robert Turcotte, MD
• India
  • New Delhi, India, 110029
    • Recruiting
    • All India Institute of Medical Science
    • Contact: Shah Alam Khan
• United States
  • California
    • Los Angeles, California, United States, 90404
      • Not yet recruiting
      • University of California - Los Angeles
      • Contact: Alexander Christ
      • Principal Investigator: Alexander Christ, MD
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University
      • Contact: Julian Dilley; Email: jedilley@indiana.edu
      • Principal Investigator: L.Daniel Wurtz, MD
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
      • Contact: Abigail Grothe; Email: abigail-grothe@uiowa.edu
      • Principal Investigator: Benjamin Miller, MD
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Recruiting
      • University of Kansas
      • Contact: Sharon Bradshaw; Email: sbradshaw2@kumc.edu
      • Principal Investigator: Kyle Sweeney, MD
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins University Hospital
      • Contact: Vaishali Laljani; Email: vparikh2@jhmi.edu
      • Principal Investigator: Adam Levin, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
      • Contact: Fernanda Canizares; Email: maria.canizares@childrens.harvard.edu
      • Principal Investigator: Megan Anderson, MD
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Alisha Sodhi; Email: asodhi1@mgh.harvard.edu
      • Principal Investigator: Santiago Lozano Calderon, MD
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
      • Principal Investigator: Megan Anderson, MD
      • Contact: Katiri Wagner; Email: kwagner@bidmc.harvard.edu
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Saint Louis University
      • Contact: David Greenberg, MD; Phone Number: 314-617-3410; Email: david.greenberg@health.slu.edu
      • Contact: Allison Gruender, RN; Phone Number: (314) 617-3406; Email: allison.gruender@health.slu.edu
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Wake Forest University
      • Principal Investigator: Cynthia Emory, MD
      • Contact: Ariel Brotherton, MA; Email: abrother@wakehealth.edu
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Contact: Kierstyn Hayden; Email: haydenk2@ccf.org
      • Contact: Heather Keaney, MPH; Email: keaneyh@ccf.org
      • Principal Investigator: Lukas Nystrom, MD
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Recruiting
      • University of Oklahoma
      • Principal Investigator: Jeremy White, MD
      • Contact: Kathy Edge; Email: Kathy-edge@ouhsc.edu
  • Oregon
    • Portland, Oregon, United States, 97239
      • Withdrawn
      • Oregon Health & Science University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Recruiting
      • Allegheny-Singer Research Institute
      • Contact: Myles Forsyth; Email: myles.forsyth@ahn.org
      • Principal Investigator: Lisa Ercolano, MD
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Withdrawn
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Primary benign GCT of bone
• Lesion located in an extremity
• 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

Exclusion Criteria:

• Recurrent GCT of bone
• Non-extremity location
• Lesion too extensive for intralesional treatment, either due to bone loss, joint invasion, or large soft tissue component
• Children and pregnancy
• Previous systemic bisphosphonate or denosumab therapy

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
No Intervention: Control group; The surgical procedure for all patients will include extensive curettage of the lesion to remove macroscopic tumor, high-speed burring of the residual cavity, adjuvant treatment to the residual cavity, followed by packing of the cavity with either polymethylmethacrylate (PMMA) bone cement (Simplex P; Stryker, Mahwah, New Jersey) alone or bone cement with subchondral allograft bone graft. The choice of cavity reconstruction will be at the discretion of the treating surgeon. Traditional local adjuvants (argon beam coagulation, phenol, ethanol, or cryotherapy) will be used depending on surgeon preference. In addition to the above standard treatment, the patients will be randomized into one of two study arms. In Arm 1, the control group, no additional local therapy will be utilized.
Experimental: Bisphosphonate group; In Arm 2, the bisphosphonate group, 4 mg of zoledronic acid (Zometa) will be added to each bag of bone cement.	Drug: Zoledronic Acid; 4 mg of zoledronic acid (Zometa) will be added to each bag of bone cement; Other Names: zoledronate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The endpoint for patient participation will be local recurrence	Local recurrence of giant cell tumor of bone	Followed for 2 years postoperatively for study end points

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MSTS Score	The Musculoskeletal Tumor Society (MSTS) scoring system is a validated and well-accepted functional scoring system used in orthopaedic oncology research	Followed for 2 years postoperatively for study end points
Surgical site infection	The surgical site will be assessed for a surgical site infection (SSI) as defined by CDC guidelines after surgery and during scheduled follow-up as outlined in time frame below.	Follow-ups will consist of clinical visits. The clinical visits will be at 2 weeks postoperatively, 6 weeks postoperatively, and then every three months for the first two years after surgery.
Wound healing	The surgical site will be assessed after surgery and during scheduled follow-up as outlined in time frame below for wound healing issues/concerns.	Follow-ups will consist of clinical visits. The clinical visits will be at 2 weeks postoperatively, 6 weeks postoperatively, and then every three months for the first two years after surgery.
Potential bisphosphonate complications related to systemic administration	Patients will be followed for atypical femur fractures and avascular necrosis (AVN) of jaw	Followed for 2 years postoperatively for study end points

Collaborators and Investigators

• Sponsor: St. Louis University
• Collaborators: Johns Hopkins University; Massachusetts General Hospital; Beth Israel Deaconess Medical Center; University of Iowa; Boston Children's Hospital; University of Oklahoma; The Cleveland Clinic; McGill University Health Centre/Research Institute of the McGill University Health Centre; Indiana University; University of Kansas; Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute); Wake Forest University; Orthopedic Research and Education Foundation; American Academy of Orthopaedic Surgeons; All India Institute of Medical Science

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2018
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: September 18, 2017
• First Submitted That Met QC Criteria: September 26, 2017
• First Posted (Actual): September 28, 2017

Study Record Updates

• Last Update Posted (Actual): October 5, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Disease Attributes; Musculoskeletal Diseases; Bone Diseases; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Recurrence; Bone Neoplasms; Giant Cell Tumors; Giant Cell Tumor of Bone; Physiological Effects of Drugs; Bone Density Conservation Agents; Zoledronic Acid
• Other Study ID Numbers: 28229

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