A Phase I Trial Assessing Several Schedules of Oral S-1 in Combination With a Fixed Dose of Oxaliplatin and Irinotecan in Patients With Advanced or Metastatic Digestive Adenocarcinoma as First- or Second-line Treatment
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Dose limiting toxicities
研究概览
简要总结
This study is to determine the Maximal Tolerated Dose (MTD), the Dose Limitant Toxicities (DLTs) and the safety profile of S-1 combined with fixed doses of Irinotecan (SIRI schedule) and fixed doses of Irinotecan and Oxaliplatin (SIRINOX schedule).
详细描述
Given the therapeutic potential and reduced toxicity advantages of S-1 compared with other fluoropyrimidines, this trial assessing S-1 with Oxaliplatin plus Irinotecan is warranted for future investigations (Phase II-III). The primary objectives are to determine the Maximal Tolerated Dose (MTD), the Dose Limitant Toxicities (DLTs) and the safety profile of S-1 combined with fixed doses of Irinotecan (SIRI schedule) and fixed doses of Irinotecan and Oxaliplatin (SIRINOX schedule).
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
- •Male or female ≥ 18 years old
- •Histologically confirmed diagnosis of advanced or metastatic digestive adenocarcinoma (gastroesophageal adenocarcinoma, colorectal adenocarcinoma, pancreatic adenocarcinoma, cholangiocarcinoma, hepatocarcinoma)
- •Metastatic or advanced disease not eligible for curative surgery
- •No active biliary obstruction
- •Previous adjuvant chemotherapy is allowed. It must be completed at least 6 months before the start of the study treatment
- •First line chemotherapy is allowed (excluding chemotherapy with Capecitabine or 5 FU or Irinotecan or Oxaliplatin). Previous Oxaliplatin is allowed in patients receiving SIRI
- •A four-week washout period since prior treatment
- •One or more measurable metastatic lesions
- •ECOG status ≤ 1
- •Total bilirubin ≤ 1.5 Upper limit of normal (ULN), ALT or AST ≤ 2.5 ULN (or < 5 in case of liver impairment)
- •Haemoglobin ≥ 10 g/dL, neutrophils ≥ 1,500/mm3, platelets ≥ 100,000/mm3 and white blood cells > 3000 /mm3
- •Lipase < 1.5 ULN, serum creatinine ≤ 1.5 ULN
- •Negative pregnancy test in women of childbearing potential
- •Use of an effective contraceptive method during the whole treatment and up to 3 months after the completion of treatment
- •Life expectancy > 3 months
- •Informed consent form (ICF) signed prior to any study specific procedures
- •Patients must be affiliated to a Social Security System
排除标准
- •History of previous treatment with Oxaliplatin except for SIRI, Irinotecan, 5 FU or Capecitabine as first-line chemotherapy
- •Peripheral sensory neuropathy ≥ grade 2 at the time of signing the ICF
- •Known central nervous system metastases
- •Unique bone metastasis
- •History or presence of other cancer within the past 5 years (except curatively treated non-melanoma skin cancer)
- •Patients with a known deficiency of the enzyme dihydropyrimidine dehydrogenase (DPD), as well as patients who, within the previous four weeks, have been treated with a medicine that inhibits this enzyme
- •Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose or galactose malabsorption
- •Malabsorption syndrome or disease significantly affecting gastro-intestinal function
- •Patient with dysphagia or inability to swallow the tablets
- •Inflammatory bowel disease with chronic diarrhoea (Grade ≥ 2 NCI CTC V4.03)
- •History of organ transplantation with use of immunosuppression therapy
- •Concomitant severe infection (> grade 2 NCI.CTCAE v4.03) or major organ failure
- •Active cardiac disease, angina pectoris or myocardial infarction in the last 6 months
- •Renal disease
- •Unstable diabetes
- •Creatinine clearance < 50 ml/min calculated using the MDRD formula
- •Pregnant or breastfeeding women
- •Participation in another clinical trial within 30 days prior to study entry
- •Psychological, social, geographical or any other condition that would preclude study compliance (treatment administration and study follow-up)
- •Legal incapacity or physical, psychological or mental status interfering with the patient's ability to sign the informed consent or to terminate the study
研究组 & 干预措施
SIRINOX
S-1: Administered orally twice daily from day 1 for 7 consecutive days followed by a 7-day recovery period in a 14-day cycle.
The starting dose of S-1 will be two levels below the recommended dose defined in SIRI (20 mg/m² BID minimum) with a cohort dose escalation by 5 mg/m² increments (5 dose levels).
Irinotecan : fixed dose of 180 mg/m² IV over 90 minutes on d1 of every cycle Oxaliplatin : fixed dose of 85 mg/m² over 120 minutes on d1 of every cycle G-csf : d8 to d13 systematically
干预措施: S-1 (Drug)
SIRINOX
S-1: Administered orally twice daily from day 1 for 7 consecutive days followed by a 7-day recovery period in a 14-day cycle.
The starting dose of S-1 will be two levels below the recommended dose defined in SIRI (20 mg/m² BID minimum) with a cohort dose escalation by 5 mg/m² increments (5 dose levels).
Irinotecan : fixed dose of 180 mg/m² IV over 90 minutes on d1 of every cycle Oxaliplatin : fixed dose of 85 mg/m² over 120 minutes on d1 of every cycle G-csf : d8 to d13 systematically
干预措施: Irinotecan (Drug)
SIRINOX
S-1: Administered orally twice daily from day 1 for 7 consecutive days followed by a 7-day recovery period in a 14-day cycle.
The starting dose of S-1 will be two levels below the recommended dose defined in SIRI (20 mg/m² BID minimum) with a cohort dose escalation by 5 mg/m² increments (5 dose levels).
Irinotecan : fixed dose of 180 mg/m² IV over 90 minutes on d1 of every cycle Oxaliplatin : fixed dose of 85 mg/m² over 120 minutes on d1 of every cycle G-csf : d8 to d13 systematically
干预措施: Oxaliplatin (Drug)
SIRINOX
S-1: Administered orally twice daily from day 1 for 7 consecutive days followed by a 7-day recovery period in a 14-day cycle.
The starting dose of S-1 will be two levels below the recommended dose defined in SIRI (20 mg/m² BID minimum) with a cohort dose escalation by 5 mg/m² increments (5 dose levels).
Irinotecan : fixed dose of 180 mg/m² IV over 90 minutes on d1 of every cycle Oxaliplatin : fixed dose of 85 mg/m² over 120 minutes on d1 of every cycle G-csf : d8 to d13 systematically
干预措施: G-csf (Other)
结局指标
主要结局
Dose limiting toxicities
时间窗: up to 5 years
Dose limiting toxicities occurring during the first two administered cycles.
次要结局
未报告次要终点