Phase I/II Study to Evaluate Nab-paclitaxel in Substitution of CPT11 or Oxaliplatin in FOLFIRINOX Schedule as First Line Treatment in Metastatic Pancreatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 148
- 试验地点
- 8
- 主要终点
- Dose finding safety and activity
研究概览
简要总结
At this moment, FOLFIRINOX is the best treatment for selected patients (pts) with metastatic pancreatic cancer (mPC). Investigator would like to evaluate the substitution of CPT11 or Oxaliplatin in FOLFIRINOX schedule with Nab-paclitaxel (Nab-p) [Nab-FOLFIRI and Nab-FOLFOX].
Doses for Nab-FOLFIRI and Nab-FOLFOX will be determined by the phase I trial. One or both schedules will be evaluated in successive phase II part.
详细描述
The primary objective for phase I of the study is to determine the MTD of Nab-p when used in substitution of OXA or CPT11 in FOLFIRINOX schedule, as first-line treatment in pts with mPC. The dose finding strategy will be based on the classical 3+3 dose escalation design.
-Analysis sets: Modified intention-to-treat population: it consists of all pts who are allocated and receive at least one dose of any component of study treatment. Pts will be grouped according to the randomized treatment assignment. Pts treated during the phase I step will be not included in this population.
Safety population: it consists of all pts who are allocated and receive at least one dose of any component of study treatment. Groups are defined by the study treatment actually received. Pts treated at the MTD during the phase I step will be not included in this population.
Statistical methods Best ORR will be summarized and 95% confidence limits will be calculated according to the exact method for each of the treatment arms included in the phase II step.
All the analyses of primary and secondary efficacy variables will be performed on the modified intention-to-treat population.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •. Males or females ≥ 18 years old and ≤ 75 years old;
- •Histological or cytological evidence of a diagnosis of pancreatic ductal adenocarcinoma;
- •Written informed consent prior to any study-specific procedures;
- •Measurable metastatic disease, defined in according to RECIST Version 1.1 (Eisenhower et al. 2009), that had not previously been treated with CT for metastatic disease;
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1 ;
- •Absence of previous abdominal radiotherapy on target lesions (except radiation therapy analgesic if it has not been performed on measurable targets);
- •Absence of heart failure or angina or infarction within 12 months previous inclusion;
- •Have adequate organ function including:
- •Hematologic: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L.
- •Hepatic: Bilirubin ≤ 1.5 times upper limits of normal (ULN) (Pts may have endoscopic or radiologic stenting to treat biliary obstructions).
- •Renal: Serum creatinine within normal limits ≤1.5 times ULN.
排除标准
- •Age of 76 years or older;
- •Endocrine or acinar pancreatic carcinoma;
- •Previous radiotherapy for measurable lesions;
- •Central nervous system metastasis;
- •Other concomitant cancer or history of cancer outside a carcinoma in situ of the cervix or basal or squamous cell of the skin;
- •Pts already included in another clinical trial with other experimental drugs;
- •Current active infection;
- •Have serious pre-existing medical conditions or serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator (for example, unstable angina pectoris, or a clinically significant history of cardiac disease or uncontrolled diabetes mellitus);
- •Females who are pregnant or lactating;
- •Unable to undergo medical test for geographical, social or psychological reason
- •Known dihydropyrimidine dehydrogenase (DPD) deficiency
研究组 & 干预措施
Nab-FOLFIRI
In the phase I study, all pts enrolled in this arm will receive Nab-FOLFIRI: Irinotecan, 180 mg per square meter of body surface area (m2 ) + Leucovorin, 400 mg/m2 and 5-Fluorouracil, 400 mg/m2 given as a bolus followed by 2400 mg/m2 given as a 46-hour continuous infusion, plus Nab-p per cohort escalation assignment starting with 90 mg/m2 every 2 weeks. Pts continued treatment until a total of 12 administrations, disease progression or unacceptable toxicity.
Pts enrolled in arm A for phase II will receive the dose of Nab-FOLFIRI as determined in the Phase I and in the same sequence.
干预措施: Paclitaxel bound albumine (Drug)
Nab-FOLFOX
In the phase I study, all pts enrolled in this arm will receive Nab-FOLFOX: Oxaliplatin 85 mg/m2 +Leucovorin, 400 mg/m2 and 5-Fluorouracil, 400 mg/m2 given as a bolus followed by 2400 mg/m2 given as a 46-hour continuous infusion, plus Nab-p per cohort escalation assignment starting with 90 mg/m2, every 2 weeks.
Pts continued treatment until a total of 12 administrations, disease progression or unacceptable toxicity.
Pts enrolled in arm B for phase II will receive the dose of Nab-FOLFOX as determined in the Phase I and in the same sequence
干预措施: Paclitaxel bound albumine (Drug)
结局指标
主要结局
Dose finding safety and activity
时间窗: 18 months
To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of the combination Nab-paclitaxel+ Irinotecan+ Leucovorin+ 5-Fluorouracil (Nab-FOLFIRI) and of the combination Nab-paclitaxel+ Oxaliplatin+ Leucovorin+ 5-Fluorouracil (Nab- FOLFOX) in pts with mPC in first-line chemotherapy (CT). To assess efficacy of Nab-FOLFIRI and Nab-FOLFOX in pts with mPC in first-line CT , in term of ORR \[Complete response (CR) + partial responses (PR)\].
次要结局
- Clinical benefit rate [CR+PR+ stable diseases (SD)](18 months)
- Safety profile(18 months)
- Progression free survival (PFS) for each schedule(18 months)
- Overall survival (OS),(18 months)
- Quality of life (QoL) for each schedule(18 months)