International collaboration is feasible in trials for rare conditions: The EURAMOS experience

Abstract

20501 Background: Osteosarcoma is rare and the outcome for patients has plateaued following the introduction of multi-agent chemotherapy. To demonstrate further improvements would likely require large numbers of patients, only achievable in this setting via International collaboration. Therefore, in October 2001, 4 multinational groups - Children's Oncology Group (COG), Cooperative Osteosarcoma Study Group (COSS), European Osteosarcoma Intergroup (EOI) and Scandinavian Sarcoma Group (SSG) - agreed on the merits of collaboration to determine whether altering post-operative therapy based on histological response improved outcome. Following a number of practical and regulatory hurdles the trial opened to accrual in April 2005. Methods: Eligibility criteria include: new diagnosis with resectable osteosarcoma; age <40 years; normal organ function. Standard therapy includes 29 weeks of cisplatin, doxorubicin and high-dose methotrexate (MAP). Following two cycles of cisplatin/doxorubicin and 2–6 cycles of high-dose methotrexate, patients undergo resection. Post-operative therapy is dependent on histological response. Good histological responders (>90% necrosis) are randomized to continuing MAP or MAP with maintenance pegylated interferon. Poor histological responders are randomized to MAP or MAP plus ifosfamide and etoposide. Results: All groups are recruiting and accrual is ahead of schedule: 373 patients have been enrolled (159 COG, 108 COSS, 83 EOI, 23 SSG) and 160 patients randomized: 87 (54%) good responders (46 MAP), 73 (46%) poor responders (39 MAP). Conclusions: International collaboration is feasible and results in rapid accrual of large number of patients. The implementation of such trials is difficult and time consuming due to the complexity of multinational regulatory issues. However, the effort is worthwhile to potentially improve outcomes for patients with rare diseases. No significant financial relationships to disclose.