A Multicenter Phase I/II Randomized Phase II Study of Gemcitabine and Nab-Paclitaxel With or Without NPC-1C in Patients With Metastatic or Locally Advanced Pancreatic Cancer Previously Treated With FOLFIRINOX
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 81
- 试验地点
- 12
- 主要终点
- Safety and Tolerability
研究概览
简要总结
This was a Phase 1/2 multi-institution prospective open label study in which subjects with metastatic, locally advanced unresectable or recurrent pancreatic cancer who previously received treatment with chemotherapy with FOLFIRINOX or FOLFIRINOX-like regimen received the investigational agent NEO-102 (NPC-1C).
The Phase 1 portion of this study evaluated the safety of NEO-102 in combination with Gemcitabine in a dose de-escalation design with a starting dose of 1.5 mg/kg/dose. If 2 of 6 patients experience DLT, the dose will be de-escalated to 1 mg/kg/dose to evaluate the safety of NEO-102 in combination with Gemcitabine. .
In the Phase 2 portion patients were randomized into one of two arms:
A: NPC-1C with gemcitabine and nab-paclitaxel or B: gemcitabine and nab-paclitaxel
详细描述
During Part 1 of the study, the safe and tolerable dose of NEO-102 in combination with Gemcitabine will be determined using a dose de-escalation design. The starting dose of NEO-102 is 1.5 mg/kg/dose (Dose level 1). If 2 of 6 patients experience a DLT at the starting dose, the dose of NEO-102 will be de-escalated to 1 mg/kg/dose, and up to 6 patients will be treated at this Dose Level -1. Upon completion of the phase I study up to 90 patients be randomized to one of two arms:
A: Patients will receive NPC-1C(NEO-102) infusion at the safe dose, and nab-paclitaxel (125 mg/m2 as a 30 minute infusion, maximum infusion time not to exceed 40 minutes) followed by gemcitabine (1000 mg/m2 as a 30 minute infusion) for 3 consecutive weeks (on Day 1, 7 and 15 ) followed by a week of rest (for a 28 day cycle).
OR B: Patients will receive on Day 1, 7 and 15 nab-paclitaxel (125 mg/m2 as a 30 minute infusion, maximum infusion time not to exceed 40 minutes) followed by gemcitabine (1000 mg/m2 as a 30 minute infusion) for 3 consecutive weeks (on Day 1, 7 and 15). NPC-1C(NEO-102) infusion at a dose of 1.5mg/kg IV 30 minutes following the completion of the gemcitabine on days 1 and 15 of the 28 day cycle.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Abraxane, gemcitabine
Nab-paclitaxel will be administered at a dose of 125 mg/m2 as a 30 minute infusion (maximum infusion time not to exceed 40 minutes) followed by 1000 mg/m2 gemcitabine as a 30 minute infusion for 3 consecutive weeks followed by a week of rest.
干预措施: Gemcitabine (Drug)
Abraxane, gemcitabine
Nab-paclitaxel will be administered at a dose of 125 mg/m2 as a 30 minute infusion (maximum infusion time not to exceed 40 minutes) followed by 1000 mg/m2 gemcitabine as a 30 minute infusion for 3 consecutive weeks followed by a week of rest.
干预措施: nab-paclitaxel (Drug)
Abraxane, gemcitabine, NPC-1C
Nab-paclitaxel will be administered at a dose of 125 mg/m2 as a 30 minute infusion (maximum infusion time not to exceed 40 minutes) followed by 1000 mg/m2 gemcitabine as a 30 minute infusion for 3 consecutive weeks followed by a week of rest.
Patients on arm B will receive NPC-1C(NEO-102) infusion at a dose of 1.5mg/kg IV on days 1 and 15 of a 4-week cycle. This will be administered 30minutes after completion of the gemcitabine infusion.
干预措施: Gemcitabine (Drug)
Abraxane, gemcitabine, NPC-1C
Nab-paclitaxel will be administered at a dose of 125 mg/m2 as a 30 minute infusion (maximum infusion time not to exceed 40 minutes) followed by 1000 mg/m2 gemcitabine as a 30 minute infusion for 3 consecutive weeks followed by a week of rest.
Patients on arm B will receive NPC-1C(NEO-102) infusion at a dose of 1.5mg/kg IV on days 1 and 15 of a 4-week cycle. This will be administered 30minutes after completion of the gemcitabine infusion.
干预措施: nab-paclitaxel (Drug)
Abraxane, gemcitabine, NPC-1C
Nab-paclitaxel will be administered at a dose of 125 mg/m2 as a 30 minute infusion (maximum infusion time not to exceed 40 minutes) followed by 1000 mg/m2 gemcitabine as a 30 minute infusion for 3 consecutive weeks followed by a week of rest.
Patients on arm B will receive NPC-1C(NEO-102) infusion at a dose of 1.5mg/kg IV on days 1 and 15 of a 4-week cycle. This will be administered 30minutes after completion of the gemcitabine infusion.
干预措施: NPC-1C (Drug)
Phase 1: Dose Finding Dose level 1
The initial portion of this protocol was a phase 1 (3+3) dose de-escalation design the initial dose of 1.5 mg/kg/dose:
Gemcitabine was administered at the dose of 1000 mg/m2 by IV infusions over 30 minutes on days 1, 8, and 15 followed in 30 minutes by NPC-1C(NEO-102) infusion at 1.5 mg/kg IV on days 1 and 15 of a 4-week cycle. Three subjects were enrolled on this dose level and all 3 subjects completed without any dose limiting toxicity. This dose was established for the Phase 2 portion of the study. At this time FDA approved the combination of Gemcitabine and Abraxane in this patient population. Hence the Phase 2 portion added Abraxane to the regimen.
干预措施: Gemcitabine (Drug)
Phase 1: Dose Finding Dose level 1
The initial portion of this protocol was a phase 1 (3+3) dose de-escalation design the initial dose of 1.5 mg/kg/dose:
Gemcitabine was administered at the dose of 1000 mg/m2 by IV infusions over 30 minutes on days 1, 8, and 15 followed in 30 minutes by NPC-1C(NEO-102) infusion at 1.5 mg/kg IV on days 1 and 15 of a 4-week cycle. Three subjects were enrolled on this dose level and all 3 subjects completed without any dose limiting toxicity. This dose was established for the Phase 2 portion of the study. At this time FDA approved the combination of Gemcitabine and Abraxane in this patient population. Hence the Phase 2 portion added Abraxane to the regimen.
干预措施: nab-paclitaxel (Drug)
Phase 1: Dose Finding Dose level 1
The initial portion of this protocol was a phase 1 (3+3) dose de-escalation design the initial dose of 1.5 mg/kg/dose:
Gemcitabine was administered at the dose of 1000 mg/m2 by IV infusions over 30 minutes on days 1, 8, and 15 followed in 30 minutes by NPC-1C(NEO-102) infusion at 1.5 mg/kg IV on days 1 and 15 of a 4-week cycle. Three subjects were enrolled on this dose level and all 3 subjects completed without any dose limiting toxicity. This dose was established for the Phase 2 portion of the study. At this time FDA approved the combination of Gemcitabine and Abraxane in this patient population. Hence the Phase 2 portion added Abraxane to the regimen.
干预措施: NPC-1C (Drug)
Phase 1: Dose Finding Dose level -1
The initial portion of this protocol was a phase 1 (3+3) dose de-escalation design the initial dose of 1.5 mg/kg/dose:
Gemcitabine was administered at the dose of 1000 mg/m2 by IV infusions over 30 minutes on days 1, 8, and 15 followed in 30 minutes by NPC-1C(NEO-102) infusion at 1 mg/kg IV on days 1 and 15 of a 4-week cycle. No patients were enrolled on this arm because Dose Level 1 was determined to be safe.
干预措施: Gemcitabine (Drug)
Phase 1: Dose Finding Dose level -1
The initial portion of this protocol was a phase 1 (3+3) dose de-escalation design the initial dose of 1.5 mg/kg/dose:
Gemcitabine was administered at the dose of 1000 mg/m2 by IV infusions over 30 minutes on days 1, 8, and 15 followed in 30 minutes by NPC-1C(NEO-102) infusion at 1 mg/kg IV on days 1 and 15 of a 4-week cycle. No patients were enrolled on this arm because Dose Level 1 was determined to be safe.
干预措施: nab-paclitaxel (Drug)
Phase 1: Dose Finding Dose level -1
The initial portion of this protocol was a phase 1 (3+3) dose de-escalation design the initial dose of 1.5 mg/kg/dose:
Gemcitabine was administered at the dose of 1000 mg/m2 by IV infusions over 30 minutes on days 1, 8, and 15 followed in 30 minutes by NPC-1C(NEO-102) infusion at 1 mg/kg IV on days 1 and 15 of a 4-week cycle. No patients were enrolled on this arm because Dose Level 1 was determined to be safe.
干预措施: NPC-1C (Drug)
结局指标
主要结局
Safety and Tolerability
时间窗: 28 days
To determine the safety and tolerability of NPC-1C monoclonal antibody therapy in combination with Gemcitabine in subjects with metastatic, locally advanced unresectable or recurrent pancreatic cancer who failed or did not tolerate first line chemotherapy of FOLFIRINOX and whose tumors bind NPC-1C.
Overall Survival
时间窗: From 1st dose of study therapy until death in participants in Phase 2.
To determine whether (only in participants in the Phase 2 portion (Arm A and Arm B) NPC-1C (NEO-102) in combination with Gemcitabine and nab-Paclitaxel will increase the overall survival (OS) compared to Gemcitabine and nab-Paclitaxel alone in patients with metastatic, locally advanced unresectable or recurrent pancreatic cancer previously treated with FOLFIRINOX and whose tumors bind NPC-1C by at least 20% on IHC.
次要结局
- Progression Free Survival(Time from the 1st dose of study drug until progression in patients in Arm A)