Clinical trial NCT00889590: Adjuvant Zoledronic Acid in High Risk Giant Cell Tumour of Bone (GCT)
Official title: Adjuvant Zoledronic Acid in 'High Risk' Giant Cell Tumour of Bone (GCT) - A Randomized Phase II Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Giant Cell Tumor of Bone
Osteoclastoma
Keywords: GCT
Bisfosfonates
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
First posted: 2009-04-29
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Determine if adjuvant zoledronic acid improves the 2 year recurrence rate of 'high risk' GCT as compared to standard care
timeFrame: 4 years
Secondary outcomes:
measure: Evaluate the usefulness of bone remodelling markers in diagnosing and monitoring GCT
timeFrame: 4 years
measure: Determine the relapse free survival
timeFrame: 4 years
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: University hospital Gent
city: Amsterdam
country: Netherlands
facility: Academic Medical Center, University of Amsterdam
city: Groningen
country: Netherlands
facility: Groningen University Medical Center
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
Study officials:
affiliation: Leiden University Medical Center (LUMC)
name: J R Kroep, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: LUMC
name: P D Dijkstra, MD PhD
role: STUDY_DIRECTOR
affiliation: LUMC
name: A H Taminiau, MD PhD
role: STUDY_DIRECTOR
affiliation: LUMC
name: P C Hogendoorn, MD PhD
role: STUDY_DIRECTOR
affiliation: LUMC
name: H Gelderblom, MD PhD
role: STUDY_DIRECTOR
affiliation: LUMC
name: N A Hamdy, MD PhD
role: STUDY_DIRECTOR
affiliation: LUMC
name: S E Papapoulos, MD PhD
role: STUDY_DIRECTOR
References:
citation: 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.