A Phase I-II Study of PAXG in Stage III-IV Pancreatic Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 137
- 试验地点
- 1
- 主要终点
- first cycle toxicity for phase I part
研究概览
简要总结
Four-drug combo yielded a statistically significant improvement in progression-free survival and overall survival compared to gemcitabine in patients with advanced pancreatic adenocarcinoma. Nab-Paclitaxel showed promising antitumor activity in patients with pancreatic cancer. Given the synergism of taxanes with gemcitabine, fluoropyrimidines and platinating agents the role of nab-Paclitaxel in a 4-drug regimen will be explored.
The aim of this trial is to determine the recommended dose of nab-paclitaxel in combination with cisplatin, capecitabine, and gemcitabine, PAXG regimen (Phase I), and to evaluate the feasibility and the activity of the PAXG regimen in patients with stage III and IV pancreatic cancer.
详细描述
OBJECTIVES: PHASE I: to determine the recommended phase 2 dose of nab-paclitaxel in combination with cisplatin, capecitabine, and gemcitabine.
PHASE II: to evaluate the feasibility and the activity of the PAXG regimen in terms of 6-months progression-free survival in patients with stage III and IV pancreatic cancer.
OUTLINE Phase I - dose finding single institution trial, followed by a randomized open label multicenter phase II trial.
Phase II: Patients will be stratified by stage (III vs IV) and CA19.9 level (< 10 x ULN versus >10 x ULN); Patients will be randomly assigned to receive PAXG (arm A) or gemcitabine-nab-paclitaxel regimen (arm B).
Treatment plan (phase II):
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
- •Pathologic diagnosis of pancreatic adenocarcinoma
- •Stage III or IV disease
- •Age > 17 < 76 years
- •Karnofsky Performance Status > 50
- •Measurable disease (only for phase II part)
- •Adequate bone marrow (GB > 3500/mm3, neutrophils > 1500/mm3; platelets > 100000/mm3; hemoglobin > 10 g/dl), liver (total bilirubin < 2 mg/dL; SGOT e SGPT < 3 UNL) and kidney function (serum creatinin < 1.5 mg/dL;)
- •Written informed consent
排除标准
- •previous chemotherapy
- •concurrent treatment with other experimental drugs
- •previous or concurrent malignancies at other sites with the exception of surgically cured carcinoma in-site of the cervix and basal or squamous cell carcinoma of the skin and of other neoplasms without evidence of disease at least from 5 years
- •symptomatic brain metastases
- •history of interstitial lung disease
- •presence of serious disease which can compromise safety (cardiac failure, previous myocardial infarction within the prior 6 months, cardiac arrhythmia, history of psychiatric disabilities)
- •pregnancy and lactating
- •History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa).
研究组 & 干预措施
PAXG regimen
cisplatin at 30 mg/m2 on days 1 and 15, nab-paclitaxel at the RP2D on days 1 and 15, capecitabine at 1250 mg/ m2 days 1-28, gemcitabine at 800 mg/ m2 on days 1 and 15 every 4 weeks
干预措施: cisplatin (Drug)
PAXG regimen
cisplatin at 30 mg/m2 on days 1 and 15, nab-paclitaxel at the RP2D on days 1 and 15, capecitabine at 1250 mg/ m2 days 1-28, gemcitabine at 800 mg/ m2 on days 1 and 15 every 4 weeks
干预措施: capecitabine (Drug)
PAXG regimen
cisplatin at 30 mg/m2 on days 1 and 15, nab-paclitaxel at the RP2D on days 1 and 15, capecitabine at 1250 mg/ m2 days 1-28, gemcitabine at 800 mg/ m2 on days 1 and 15 every 4 weeks
干预措施: gemcitabine (Drug)
PAXG regimen
cisplatin at 30 mg/m2 on days 1 and 15, nab-paclitaxel at the RP2D on days 1 and 15, capecitabine at 1250 mg/ m2 days 1-28, gemcitabine at 800 mg/ m2 on days 1 and 15 every 4 weeks
干预措施: nab-paclitaxel (Drug)
gemcitabine + nab-paclitaxel
gemcitabine at 1000 mg/ m2 on days 1, 8 and 15 every 4 weeks + nab-paclitaxel at 125 mg/ m2 on days 1, 8 and 15 every 4 weeks
干预措施: gemcitabine (Drug)
gemcitabine + nab-paclitaxel
gemcitabine at 1000 mg/ m2 on days 1, 8 and 15 every 4 weeks + nab-paclitaxel at 125 mg/ m2 on days 1, 8 and 15 every 4 weeks
干预措施: nab-paclitaxel (Drug)
结局指标
主要结局
first cycle toxicity for phase I part
时间窗: after one month from treatment start
Dose Limiting Toxicity definition: DLT will be defined as any of the following events attributable to the administered study drugs: * Hematologic toxicity * Grade ≥ 4 neutropenia lasting 7 days or more * Grade ≥ 3 febrile neutropenia or fever of unknown origin ≥ 38.5°C * Grade 4 thrombocytopenia * Grade 3 thrombocytopenia which required transfusions * Nausea or vomiting Grade ≥ 3 nausea or vomiting despite maximal antiemetic therapy * Diarrhea Grade ≥ 3 diarrhea despite optimal management of the event * Neurological toxicity Any Grade ≥ 2 neurological toxicity * Other non-hematologic toxicity Any grade ≥ 3 toxicities or representing a shift by 2 grades from baseline (in case of abnormal baseline) * Failure to recover Failure to recover to grade ≤ 1 toxicity (except alopecia) or to baseline values after delaying the initiation of next cycle by \> 2 weeks.
progression-free survival for phase II part, stage IV patients
时间窗: after 6 months from randomization
rate of progression-free patients at 6 months from randomization
resectability rate for phase II part, stage III patients
时间窗: after 4 and 6 months from treatment start
rate of resectable patients at at time of CT evaluation and multidisciplinary assessment after 4 and 6 months from treatment start
次要结局
- response rate(every two months up to 6 months during treatment; every 2-3 months afterwards until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months)
- toxicity(every two weeks up to 26 weeks during treatment)
- biochemical response rate(every month up to 6 months during treatment; every 2-3 months afterwards until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months)
- overall survival(From date of trial enrolment until the date of death from any cause, assessed every two weeks up to 26 weeks during treatment; every 2-3 months afterwards up to 60 months)
- Progression-free survival(From date of trial enrolment until the date of documented progression or date of death from any cause, whichever came first, assessed every two months up to 6 months during treatment; every 2-3 months afterwards up to 60 months)
研究者
Michele Reni
Principal Investigator
IRCCS San Raffaele