Phase II Study of Combined Chemotherapy With Arsenic Trioxide in Stage 4/M Neuroblastoma

Clinical Research on Efficacy and Safety of Combined Chemotherapy With Arsenic Trioxide in Stage 4/M Neuroblastoma：A Prospective，Single-arm, Open-label, Multi-center Study

This clinical trial aims to explore and evaluate the efficacy and safety of combined chemotherapy with arsenic trioxide for stage 4/M neuroblastoma.

This study is a prospective, single-arm, open-lable, multi-center clinical trial. Children≤ 14 years old are eligible for this study if they were newly diagnosed with neuroblastoma and assessed as stage 4 according to the International Neuroblastoma Staging System (INSS) or stage M according to the International Neuroblastoma Risk Group (INRG) respectively. Patients enrolled in this study will receive combined induction chemotherapy with arsenic trioxide following an modifed protocol based on N7 and NB2004 protocols. Objective response rate (ORR) at 4 weeks after completing induction chemotherapy was defined as the main outcome and adverse events were monitored and graded in the meantime.

Arsenic trioxide（ATO） is administered 0.16mg/kg per day over eight hours IV daily for ten days. Patients will receive ATO alone on days 1-2 and combined with conventional induction chemotherapy on days 3-10. Nine cycles at most of ATO-combined chemotherapy were applied in the whole scheme.

From the date of patients enrolled until the date of death from any cause，From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.

Survival time from patients diagnosed with stage 4/M neuroblastoma untill disease progression or death

From the date of patients enrolled to the date of of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.

Adverse events are monitored and graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)

From date of ATO-combined chemotherapy until the date of first documented adverse event, and follow up for 3 years.

Inclusion Criteria: Untreated Stage 4/M neuroblastoma patients according to the International Neuroblastoma Staging System（INSS) or the International Neuroblastoma Risk Group (INRG) staging system; Patients not more than 14 years old; There are measurable lesions; Guardians agreed and signed informed consent. Exclusion Criteria: Patients who had suffered from other tumors and received chemotherapy or abdominal radiotherapy. Patients with one or more critical organs failure such as heart, brain, kidney failure.