Giant Cell Tumor of Bone (GCTB) is a rare tumor known to be locally aggressive, but rarely metastasizing. Resectable GCTB without possible postoperative large bone defect has been treated by curettage with local adjuvant treatment, and its recurrence rate is as high as 20-30%. A recent phase II study demonstrated the effects of denosumab for patients with unresectable GCTB and resectable GCTB with possible postoperative large bone defect. However, the efficacy of preoperative denosumab for GCTB without possible postoperative large bone defect is still controversial. Therefore, we have commenced a phase III trial to confirm the superiority of preoperative denosumab for patients with GCTB who can be treated with curettage.
Eligibility criteria include histologically proven GCTB, arising in the extremity, primary tumor (Campanacci grade II or III) and first or second local recurrent tumor, tumor which can be treated by curettage, no distant metastases, and aged 20 to 70. Patients are randomized to either arm A (curettage and adjuvant local therapy) or arm B (preoperative denosumab, curettage, and adjuvant local therapy). Preoperative denosumab is administered subcutaneously at a dose of 120 mg on day 1, 8, 15, 29, and 57. Only in a case of insufficient bone formation after 5 times of denosumab, it is allowed to add denosumab 3 times. The primary endpoint is relapse-free survival (RFS). Secondary endpoints include overall survival, joint-preserved survival, local relapse-free survival, metastasis-free survival, adverse events, serious adverse events, surgical and postoperative complications, and discontinuation of denosumab. We assume that the proportion of RFS at 3 years is 80% for arm A and expect a 10% increase in the proportion of RFS at 3 years for arm B. A sample size was calculated as 51 patients per arm to observe 25 total events with a one-sided alpha level of 10%, power of 70%, an accrual period of 5 years, and a follow-up period of 3 years. Thus, the total sample size was defined as 106 patients to account for loss to follow-up. This trial has started in October 2017 and current enrollment is 3 patients in April 2018.
Clinical trial identification
UMIN000029451 (release date: 6. Oct. 2017).
Legal entity responsible for the study
Japan Clinical Oncology Group (JCOG).
National Cancer Center, Japan.
H. Urakawa: Honoraria: Astellas Pharma, J. Eba: Honoraria: Chugai Pharma (to an immediate family member). H. Hiraga: Honoraria: Taiho Pharmaceutical, Celgene, Eisai, Hisamitsu Pharmaceutical, Secom Medical System, Astellas Pharma; Research funding to institution: Lilly Japan. A. Kawai: Consulting or advisory role: Novartis, Lilly, Taiho Pharmaceutical, Ignyta; Honoraria: Novartis, Takara Bio, Taiho Pharmaceutical, Eisai, Lilly. Y. Nishida: Consulting or advisory role: Seikagaku; Speakers' bureau: Stryker, Novartis, Eisai, Lilly Pharma; Travel, accommodations, expenses: Taisho Toyama Pharma. H. Fukuda: Honoraria: Taiho Pharmaceutical, Chugai Pharma. All other authors have declared no conflicts of interest.