A Randomized, Open-label Phase 2 Study of Nanoliposomal Irinotecan (Nal-IRI)-Containing Regimens Versus Nab-Paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Ipsen
- 入组人数
- 56
- 试验地点
- 36
- 主要终点
- Part 1A: Number of Participants With Dose-Limiting Toxicities (DLT)
研究概览
简要总结
This is an open-label, phase 2 non-comparative study to assess the safety, tolerability, and preliminary efficacy of nal-IRI in combination with other anticancer therapies in patients not previously treated for metastatic pancreatic adenocarcinoma. This study will assess the following regimen:
• nal-IRI + 5-fluorouracil (5-FU)/leucovorin (LV) + oxaliplatin
The study will be conducted in two parts:
Part 1, consisting of an initial dose exploration (Part 1A) followed by dose expansion (Part 1B) of the irinotecan liposome injection +5-FU/LV + oxaliplatin regimen and Part 2, consisting of a comparison of irinotecan liposome injection-containing regimen versus nab-paclitaxel plus gemcitabine. The comparative Part 2 was removed in a protocol amendment, dated 11 April 2018 (Version 6.0), before it was initiated, as this comparative part of the study is being undertaken as a stand-alone phase III study D-US-60010-001. This CSR only pertains to the single-arm dose exploration and dose expansion Part 1 results and no further reference is made to the comparative Part 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Histologically or cytologically confirmed adenocarcinoma of the pancreas that has not been previously treated in the metastatic setting
- •Unresectable, locally advanced or metastatic disease; diagnosed within 6 weeks prior to screening
- •At least one tumor lesion measurable by CT or MRI scan (according to RECIST v1.1)
- •ECOG performance status of 0 or 1 at screening and within 72 hours prior to first dose if first dose occurs more than 72 hours post-screening
- •Adequate hematological, hepatic, renal and cardiac function
- •Recovered from the effects of any prior surgery or radiotherapy
- •Patient has a Karnofsky performance status (KPS) ≥ 70 at Screening, and within 72 hours prior to date of first dose if first dose occurs more than 72 hours after screening (Part 1B only)
排除标准
- •Prior treatment of pancreatic cancer in the metastatic setting (or locally advanced setting) with surgery (placement of stent is allowed), radiotherapy, chemotherapy or investigational therapy
- •Prior treatment of pancreatic cancer with chemotherapy in adjuvant setting, except those where at least 12 months have elapsed since completion of the last dose and no persistent treatment-related toxicities present
- •Uncontrolled Central Nervous System (CNS) metastases
- •Clinically significant gastrointestinal disorder
- •History of any second malignancy in the last 3 years. Patients with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible
- •Presence of any contraindications for nal-IRI, irinotecan, 5-FU, leucovorin, oxaliplatin
- •Use of strong CYP3A4 or inducers or presence of any other contra indications for irinotecan
- •Pregnant or breast feeding
- •Neuroendocrine or acinar pancreatic carcinoma
- •Serum albumin < 3 g/dL at screening visit and within 72 hours prior to first dose if first dose occurs more than 72 hours post screening
- •Patients with symptoms and signs of clinically unacceptable deterioration of primary disease at time of screening
- •Previous treatment with irinotecan-based, nab-paclitaxel-based or gemcitabine-based resulting in disease progression
研究组 & 干预措施
nal-IRI + 5-FU/LV + oxaliplatin
干预措施: nal-IRI (Drug)
nal-IRI + 5-FU/LV + oxaliplatin
干预措施: 5 fluorouracil (Drug)
nal-IRI + 5-FU/LV + oxaliplatin
干预措施: Leucovorin (Drug)
nal-IRI + 5-FU/LV + oxaliplatin
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
Part 1A: Number of Participants With Dose-Limiting Toxicities (DLT)
时间窗: From the start of the first study treatment (Cycle 1 Day 1) up to 14 days after the second dose of study treatment, maximum of 42 days
Adverse events (AEs) were considered to be DLTs if they occurred during the safety evaluation period (i.e, 28 days of Cycle 1; or 14 days after the second dose of study treatment if there was a treatment delay) and were deemed related to the study treatment regimen. Any AE that was related to disease progression was not considered a DLT.
次要结局
- Disease Control Rate (DCR)(At Week 16)
- Median Progression Free Survival (PFS)(RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, end of treatment (EoT) visit, then every 2 months thereafter (maximum of 278 weeks).)
- Best Overall Response (BOR)(RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).)
- Overall Response Rate (ORR)(RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).)
- Median Overall Survival (OS)(RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).)
- Median Duration of Response (DoR)(RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).)