Observational, Noninterventional Surveillance Study of Patients with High-Grade Osteosarcoma who are Candidates for Liposomal Mifamurtide Treatment

ABSTRACT Background Although surgery is the mainstay of osteosarcoma treatment, it is generally not curative and prognosis is poor. Survival rates improved with the introduction of adjuvant and neoadjuvant chemotherapy but have remained largely unchanged since the 1980s. Mifamurtide is a liposomal formulation of muramyl tripeptide phosphatidyl ethanolamine, which stimulates macrophages and monocytes, resulting in tumoricidal effects. In a phase 3 trial in 678 patients with newly diagnosed high-grade osteosarcoma, mifamurtide given post-resection in combination with chemotherapy improved 6-year overall survival probability to 77% vs. 66% with chemotherapy alone (p = 0.03; mifamurtide assessment report [www.ema.europa.eu]). The most common grade 3/4 adverse events (AEs) were cytopenias, stomatitis and infections, with no difference between the treatment arms for most toxicities reported (www.ema.europa.eu). Methods This phase 4 study will assess osteosarcoma patients who are candidates for mifamurtide therapy at European centres. (EudraCT: 2009-017204-89;NCT01194284). Eligible patients are aged 2–30 years, with a confirmed diagnosis of high-grade osteosarcoma. Approximately 150 patients are planned to be entered, and recruited over a 2-year period. Patients will receive the standard schedule of 2 mg/m2 IV mifamurtide, administered twice weekly for 12 weeks then once weekly for 24 weeks (total 36 weeks). The primary objectives are to assess the short- (during treatment) and long-term (≤5 years from last mifamurtide dose or until death) safety profile of mifamurtide, including evaluation of AEs of special interest (defined as important identified and potential risks) to take into account the risk of recurrence and comorbidities with chemotherapy. Secondary objectives include assessment of disease status, disease-free survival and overall survival. Disclosure C. Oliva: Employment: Takeda. Y. Liu: Employment: Millennium. All other authors have declared no conflicts of interest.