Phase I Trial of OXIRI [Oxaliplatin (O), Xeloda (X) and Irinotecan (I)] Treatment in Patients With Advanced and/or Metastatic Pancreatic Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Safety and tolerability of the OXIRI regimen as measured by the frequency of significant adverse events incurred by the participants, using CTCAE ver. 4 grading system
研究概览
简要总结
This is an exploratory Phase I study is to assess the safety and tolerability of the OXIRI regimen [oxaliplatin (O), xeloda (X) and irinotecan (I)] and to evaluate for preliminary evidence of efficacy, in patients with advanced and/or metastatic pancreatic adenocarcinoma. The investigators hypothesize that 2 of 3 weekly doses of oxaliplatin and genotype directed-dosing of irinotecan in combination with chronomodulated capecitabine (xeloda) administered continuously will be more tolerable than the FOLFIRINOX regimen (folinic acid, fluorouracil, irinotecan and oxaliplatin) while maintaining anti-tumour activity.
详细描述
This study comprises a dose escalation phase using 3+3 design to determine the safety, tolerability and pharmacokinetics of the OXIRI regimen and an expansion phase to further evaluate the MTD and to determine early signs of efficacy.
Eligible patients will receive a novel chemotherapeutic regimen (OXIRI regimen) with xeloda being administered in a chronomodulated fashion and the dose of irinotecan being guided by the UGT1A1*28 and UGT1A1*6 genotype status of the patient.
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
- 21 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients between 21 to 75 years of age
- •A histopathologically or cytological confirmed diagnosis of locally advanced and/or metastatic PDAC that is unresectable
- •Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) ver 1.1 criteria
- •Life expectancy of at least 12 weeks
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- •Adequate hematologic function (neutrophils count ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L)
- •Adequate hepatic function (total bilirubin ≤ 1.5 x the upper limits of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN
- •Adequate renal function (calculated creatinine clearance > 50 mL/min)
- •Able to give informed consent
- •Toxicity related to previous radiotherapy or chemotherapy resolved to ≤ Grade 1
排除标准
- •History of prior malignancy except non-melanoma skin cancer within the last 5yrs
- •Uncontrolled central nervous system (CNS) metastases or carcinomatous meningitis
- •Uncontrolled concomitant medical illnesses (e.g. hypertension, myocardial infarct, heart failure, ventricular arrhythmia, diabetes, severe infection)
- •Major surgery within four weeks prior to study treatment
- •Patients on chronic immunosuppressive therapy
- •Pregnant or breast-feeding female patients
- •On anticoagulant therapy with vitamin K antagonists.
- •Dose-escalation cohort:
- •Patients homozygous for uridine diphosphate glucuronosyltransferase (UGT)1A1*6/*6 or UGT1A1*28/*28
- •Previous oxaliplatin or irinotecan chemotherapy
- •Treatment with any of the following anti-cancer therapies prior to the first dose of OXIRI within the stated timeframes
- •Cyclical chemotherapy within a period of time that is shorter than the cycle length used for that treatment. Exception for weekly chemotherapy regimens, where a minimum of 2 week washout from the last dose is required.
- •Biological therapy (e.g., antibodies) within a period of time that is ≤ 5 t1/2 or ≤ 4 weeks, whichever is shorter, prior to starting study drug
- •Continuous or intermittent small molecule therapeutics within a period of time that is ≤ 5 t1/2 or ≤ 4 weeks (whichever is shorter) prior to starting study drug
- •Any other investigational agents within a period of time that is ≤ 5 t1/2 or less than the cycle length used for that treatment or ≤ 4 weeks (whichever is shortest) prior to starting study drug
- •Wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug
- •Dose-expansion cohort:
- •Previous chemotherapy or radiotherapy
研究组 & 干预措施
OXIRI
OXIRI regimen: oxaliplatin, irinotecan, capecitabine
干预措施: oxaliplatin, irinotecan, capecitabine (Drug)
结局指标
主要结局
Safety and tolerability of the OXIRI regimen as measured by the frequency of significant adverse events incurred by the participants, using CTCAE ver. 4 grading system
时间窗: from first dose to 30 days after last dose
The safety and tolerability of the regimen will be assessed when the patient is on treatment and till 30 days after treatment.
次要结局
- Pharmacokinetics analysis of capecitabine(cycle 1 day 1)
- Maximum tolerated dose (MTD) of capecitabine when administered in a continuous chronomodulated fashion with genotype-directed dosing of irinotecan and metronomic dosing of oxaliplatin, using a conventional 3+3 design(2 years)
- Efficacy of OXIRI as measured by response evaluation criteria in solid tumours (RECIST) version 1.1(3 years)
- Recommended Phase II dose (RP2D) of the OXIRI regimen which is the MTD(2 years)
- Pharmacokinetics analysis of Irinotecan(cycle 1 day 1)