Adjuvant Zoledronic Acid in High Risk Giant Cell Tumour of Bone (GCT) (HR-GCT)

Adjuvant Zoledronic Acid in 'High Risk' Giant Cell Tumour of Bone (GCT) - A Randomized Phase II Study

This is a multicenter, randomised phase II trial in patients with high risk GCT.

Primary objective:

• Determine if adjuvant zoledronic acid improves the 2 years recurrence rate of 'high risk' GCT as compared to standard care

Secondary objectives:

• Determine the relapse free survival
• Evaluate the usefulness of bone remodelling markers in diagnosing and monitoring GCT

Study Overview

• Status: Terminated
• Conditions: Giant Cell Tumor of Bone; Osteoclastoma
• Intervention / Treatment: Drug: Zoledronic acid

Detailed Description

GCT is a potentially malignant tumour that presents with a locally destructive osteolytic lesion. The high risk GCT are characterized by a high recurrence rate around the 40-45%. Zoledronic acid is a potent inhibitor of osteolysis and is capable of inducing osteoclast and stromal cell apoptosis, which makes it an attractive adjuvant treatment in 'high risk' GCT in order to improve clinical outcomes and reduce the recurrence rate.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • University Hospital Gent
• Netherlands
  • Amsterdam, Netherlands, 1100DD
    • Academic Medical Center, University of Amsterdam
  • Groningen, Netherlands, 9700 RB
    • Groningen University Medical Center
  • Leiden, Netherlands, 2300RC
    • Leiden University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed written informed consent
• Male or female > 18 years of age
• Histologically proven GCT treated with surgery

• High risk GCT defined as minimal one or more of the following:

  • Recurrent GCT
  • GCT located in the pelvis, sacrum, spine, distal ulna or growth in soft tissue
  • GCT grade III
  • Pathological fracture in GCT
  • Absence of local adjuvant therapy (cryosurgery or phenol instillation)
• Neutrophils > 1.5x109/L, platelets > 100x109/L, and Hb > 6 mmol/l
• Bilirubin level < 1.5 x ULN
• ASAT and ALAT < 2.5 x ULN
• Adequate renal function as defined by: serum creatinine clearance > 60 cc/min
• Expected adequacy of follow-up

Exclusion Criteria:

• Unresectable or metastatic GCT and grade IV GCT
• Prior bisphosphonate usage, except preoperative treatment with zoledronic acid up to 3 months before surgery
• Other previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix
• Known hypersensitivity reaction to any of the components of the treatment
• Pregnancy or lactating
• Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Standard care
Experimental: Zoledronic acid; Adjuvant zoledronic acid	Drug: Zoledronic acid; 4 mg, monthly for 3 months followed by a 3-monthly schedule for up to one year after surgery; Other Names: Zometa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determine if adjuvant zoledronic acid improves the 2 year recurrence rate of 'high risk' GCT as compared to standard care	4 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Evaluate the usefulness of bone remodelling markers in diagnosing and monitoring GCT	4 years
Determine the relapse free survival	4 years

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Investigators: Principal Investigator: J R Kroep, MD PhD, Leiden University Medical Center (LUMC); Study Director: P D Dijkstra, MD PhD, LUMC; Study Director: A H Taminiau, MD PhD, LUMC; Study Director: P C Hogendoorn, MD PhD, LUMC; Study Director: H Gelderblom, MD PhD, LUMC; Study Director: N A Hamdy, MD PhD, LUMC; Study Director: S E Papapoulos, MD PhD, LUMC

Publications and helpful links

General Publications

• Lipplaa A, Kroep JR, van der Heijden L, Jutte PC, Hogendoorn PCW, Dijkstra S, Gelderblom H. Adjuvant Zoledronic Acid in High-Risk Giant Cell Tumor of Bone: A Multicenter Randomized Phase II Trial. Oncologist. 2019 Jul;24(7):889-e421. doi: 10.1634/theoncologist.2019-0280. Epub 2019 Apr 30.

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: April 28, 2009
• First Submitted That Met QC Criteria: April 28, 2009
• First Posted (Estimate): April 29, 2009

Study Record Updates

• Last Update Posted (Estimate): January 26, 2016
• Last Update Submitted That Met QC Criteria: January 25, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: GCT; Bisfosfonates
• 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; Bone Density Conservation Agents; Zoledronic Acid
• Other Study ID Numbers: P08.185