Abstract：
BACKGROUND: This multicenter Phase I study (NCT03585465) evaluated nivolumab in combination with 3 metronomic chemotherapy (MC) regimens in children with refractory/relapsing solid tumors.
OBJECTIVE: To evaluate the feasibility and safety of the three regimens METHODS: Patients aged < 18 years were enrolled. Nivolumab was combined with cyclophosphamide and vinblastine (arm A), capecitabine (arm B), or cyclophosphamide, vinblastine and capecitabine (arm C). Arm A and B were allocated sequentially. Arm C opened only if A and B were deemed safe. Dose-limiting toxicities (DLTs) were evaluated over the first two cycles. Patients were evaluable if they received > 2 cycles and > 70% of the planned dose.
METHODS: Sixteen patients were enrolled, 3 in arm A, 6 in arm B, and 7 in arm C. Median age was 11.5 years (range, 5-19). Patients previously received a median of 3.5 (range, 1-4) lines of systemic treatment, 14 patients had surgery and 11 had radiotherapy.
RESULTS: Median number of cycles was 2 (1-24), median treatment duration was 56 days (18-714). In arm C, median number of cycles was 4 with median treatment duration of 95 days. No DLT was observed. Grade 3 adverse events (AE) and serious AE were observed in 8 patients (50%) and 1 patient (6%), respectively, over the first 2 cycles. No grade 4 AE occurred. The 6-month PFS and OS were 12% and 44%, respectively, in the whole population. Prolonged stable disease was observed in a high-grade glioma and an atypical teratoid rhabdoid tumor.
CONCLUSIONS: Arm C appears safe. A randomized phase II trial evaluating the addition of nivolumab to the triple MC is ongoing.
OBJECTIVE: To evaluate the feasibility and safety of the three regimens METHODS: Patients aged < 18 years were enrolled. Nivolumab was combined with cyclophosphamide and vinblastine (arm A), capecitabine (arm B), or cyclophosphamide, vinblastine and capecitabine (arm C). Arm A and B were allocated sequentially. Arm C opened only if A and B were deemed safe. Dose-limiting toxicities (DLTs) were evaluated over the first two cycles. Patients were evaluable if they received > 2 cycles and > 70% of the planned dose.
METHODS: Sixteen patients were enrolled, 3 in arm A, 6 in arm B, and 7 in arm C. Median age was 11.5 years (range, 5-19). Patients previously received a median of 3.5 (range, 1-4) lines of systemic treatment, 14 patients had surgery and 11 had radiotherapy.
RESULTS: Median number of cycles was 2 (1-24), median treatment duration was 56 days (18-714). In arm C, median number of cycles was 4 with median treatment duration of 95 days. No DLT was observed. Grade 3 adverse events (AE) and serious AE were observed in 8 patients (50%) and 1 patient (6%), respectively, over the first 2 cycles. No grade 4 AE occurred. The 6-month PFS and OS were 12% and 44%, respectively, in the whole population. Prolonged stable disease was observed in a high-grade glioma and an atypical teratoid rhabdoid tumor.
CONCLUSIONS: Arm C appears safe. A randomized phase II trial evaluating the addition of nivolumab to the triple MC is ongoing.
摘要：
背景：这项多中心I期研究（NCT03585465）评估了纳武单抗联合3种节拍化疗（MC）方案在难治性/复发性实体瘤儿童中的应用。
目的：评估三种治疗方案的可行性和安全性方法：纳入年龄<18岁的患者。Nivolumab联合环磷酰胺和长春碱（A组），卡培他滨（B组），或者环磷酰胺,长春碱和卡培他滨（C组）。A和B组依次分配。只有在A和B被认为是安全的情况下，C臂才会打开。在前两个循环中评估剂量限制性毒性(DLT)。如果患者接受>2个周期和>70%的计划剂量，则可评估。
方法：纳入16例患者，3在A臂中，6在B臂中，臂C为7岁，中位年龄为11.5岁(范围，5-19).患者先前接受的中位数为3.5（范围，1-4）全身治疗线，14例接受手术治疗，11例接受放疗。
结果：周期的中位数为2（1-24），中位治疗持续时间为56天(18-714).在C臂,中位周期数为4个,中位治疗持续时间为95天.没有观察到DLT。在8例患者(50%)和1例患者(6%)中观察到3级不良事件(AE)和严重AE,分别,在前两个周期。没有发生4级AE。6个月PFS和OS分别为12%和44%，分别,在整个人口中。在高级别神经胶质瘤和非典型畸胎瘤中观察到长期稳定的疾病。
结论：C臂看起来是安全的。正在进行一项评估在三重MC中添加nivolumab的随机II期试验。
目的：评估三种治疗方案的可行性和安全性方法：纳入年龄<18岁的患者。Nivolumab联合环磷酰胺和长春碱（A组），卡培他滨（B组），或者环磷酰胺,长春碱和卡培他滨（C组）。A和B组依次分配。只有在A和B被认为是安全的情况下，C臂才会打开。在前两个循环中评估剂量限制性毒性(DLT)。如果患者接受>2个周期和>70%的计划剂量，则可评估。
方法：纳入16例患者，3在A臂中，6在B臂中，臂C为7岁，中位年龄为11.5岁(范围，5-19).患者先前接受的中位数为3.5（范围，1-4）全身治疗线，14例接受手术治疗，11例接受放疗。
结果：周期的中位数为2（1-24），中位治疗持续时间为56天(18-714).在C臂,中位周期数为4个,中位治疗持续时间为95天.没有观察到DLT。在8例患者(50%)和1例患者(6%)中观察到3级不良事件(AE)和严重AE,分别,在前两个周期。没有发生4级AE。6个月PFS和OS分别为12%和44%，分别,在整个人口中。在高级别神经胶质瘤和非典型畸胎瘤中观察到长期稳定的疾病。
结论：C臂看起来是安全的。正在进行一项评估在三重MC中添加nivolumab的随机II期试验。
