Study of the Effect of Zoledronate on Local Recurrence After Surgical Treatment of Giant Cell Tumors of Bone Zométa (Zometa)

Phase 2 Study of the Effect of Zoledronate on Local Recurrence After Surgical Treatment of Giant Cell Tumors of Bone

The giant cell tumor (GTC) is an aggressive benign bone tumor, growing at the metaphyseal-epiphyseal regions of long bones, especially around the knee and the distal radius.It is responsible for bony destruction in para-articular zone fracture and leading to the breakdown and destruction of the underlying joint.

Histologically, the tumor cell contains a contingent of monocytic cells round, a contingent of giant type cell of type osteoclastic responsible for bone resorption that accompanies these tumors and a contingent of lengthened cells fibroblast-like considered to be contingent tumor.

The treatment is exclusively surgical; or by resection of the lesion which takes away tumour and its environment, solution which, if it prevents local recurrence, imposes an important bony and articular reconstruction, always limited and deteriorating rapidly over time in these young patients; or by curettage of lesion, by "hollowing-out" of the bone, creating a hole which it will be necessary to fill up by a bony grafting or a substitute of the bone (cement). This last solution, if it preserves a better function, exposes at risk of local recurrence,putting into play the prognosis of articulation near, most often the knee.Despite different local adjuvants treatments used during surgical operation, after having curetted the cavity and before filling it up, the recidivism rates vary from 12 % to 41 % (average 25 %) in literature.

The beneficial effect of the adjuvants therapeutics suggests the concept broadly accepted by a tumoral microscopic residual at the origin of the local recidivism .Biphosphonates (BP) is molecules which settle in vivo on the hydroxyapatite of the bone; they inhibit the recruitment of the osteoclast forerunners and the activity of mature osteoclast. Besides, biphosphonates containing some nitrogen (N-BP), leads to the apoptose of mature osteoclast. These molecules also have a direct effect on tumor cells , causing apoptosis of neoplastic cells of myeloma, of breast cancer. Clinical controlled studies confirm the experimental data of N-BP. Two work also showed their effect on osteoclasts and stroma cells of tumours with giant cells but no clinical study assessed potential on the prevention of the local recurrence.

The investigators offer a study phase 2 of the effectiveness of N-BP (acid zoledronique) on the prevention of the local recurrence of tumours with primary huge cells after surgical treatment by curettage - filing by a surgeon referent in oncologic orthopedic surgery.

Number of patients: 24

Study Overview

• Status: Terminated
• Conditions: Giant Cell Tumors of Bone
• Intervention / Treatment: Drug: acid Zoledronic

Detailed Description

Outcome Measures:

- Main: occurrence of recurrence detectable by Reasonable Magnetic Imaging (IRM) and / or standardized radiography.

Local recurrence will be discussed in the presence or appearance on the radiographic and IRM monitoring of an osteolysis in the periphery of the cavity curetted, does not exist on the radio in post-operative with IRM signal abnormalities in the same location,taking the gadolinium. If in doubt, a new surgical biopsy will confirm or not the diagnosis of local recurrence

secondary:

• clinical: patient interview, clinical examination
• biological Complete blood count, creatinine, serum calcium, phosphate, magnesium

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Nantes, France
    • CHU de Nantes

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:

• Patient age (18 years)
• Benign giant cell tumor of the bone histologically confirmed after biopsy
• Non-metastatic tumor
• The first surgical treatment of the tumor
• Indication of conservative treatment with curettage, filling asked by the surgeon investigator
• Written consent of the patient

Exclusion Criteria:

• Minor patient
• Location of a pulmonary TCG
• Surgical indication of prior or immediately en bloc resection
• Need for treatment with an aminoglycoside
• Against-indication for zoledronic acid: pregnancy, lactation, known hypersensitivity to this drug or another bisphosphonate, severe renal impairment or a previous kidney failure, severe bradycardia or conduction disturbance on ECG.
• Dental Problems in progress, including an infection of the teeth or jaw underlying (mandible and maxilla), dental trauma or recent diagnosis or history of osteo-necrosis of the jaw (ONJ) , or exposure of the OSE or delayed healing after dental procedures.
• Dental or jaw bone recent (within 6 weeks) or planned (extractions, implants, ...).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Decrease in the recurrence rate of GTC of the bone after surgery (efficacy).	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerance at the filling treatment with zoledronic acid (safety).	Clinical examination of the patient, clinical examination (confusing yes / no, headache yes / no, visual yes / no, nausea yes / no, vomiting yes / no, itching rash yes / no, arthralgia yes / no, bone pain yes / no, bradycardia <60 during the infusion yes / no, fever yes / no, taste thirst yes / no, chest pain yes / no); Organic: blood count (NFS), creatinine, serum calcium, phosphate, magnesium (below the standards of the laboratory that conducted the review yes / no)	36 months

Collaborators and Investigators

• Sponsor: Nantes University Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: June 28, 2011
• First Submitted That Met QC Criteria: March 23, 2012
• First Posted (Estimate): March 27, 2012

Study Record Updates

• Last Update Posted (Estimate): August 30, 2013
• Last Update Submitted That Met QC Criteria: August 29, 2013
• Last Verified: August 1, 2013

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
• Other Study ID Numbers: 04/10-E