A Randomized Phase III Trial Comparing Chemotherapy With Folfirinox to Gemcitabine in Locally Advanced Pancreatic Carcinoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- UNICANCER
- 入组人数
- 171
- 试验地点
- 45
- 主要终点
- Progression-Free-Survival (PFS)
研究概览
简要总结
French national multicentric phase III trial evaluating chemotherapy with Folfirinox or gemcitabine in locally advanced pancreatic carcinoma.
详细描述
Comparative interventional prospective phase 3, randomized, open-label, multicentric trial comparing chemotherapy with Folfirinox to Gemcitabine in locally advanced pancreatic carcinoma.
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 —（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
- •Proven unresectability after multidisciplinary discussion involving radiologist and a surgeon
- •Locally advanced (i.e.: no metastasis or suspicion of metastasis) and unresectable tumors: for example mesenteric or portal vein involvement, or > 180° encasement of the superior mesenteric artery, or celiac abutment (NCCN 2012 criteria)
- •Measurable tumor lesions with longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm with spiral CT scan according RECIST 1.1
- •WHO Performance status (PS) 0-1
- •Age ≥18 years
- •Patient with organ function as follows:
- •Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L
- •Hemoglobin ≥ 10 g/dL
- •Platelets (PTL) ≥ 75 x 10⁹/L
- •Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
- •Bilirubin ≤ 1.5 x ULN
- •Creatinine ≤ 2 x ULN
- •Albumin > 0.75 x lower limit of normal (LLN)
- •Urea ≤ 2 x ULN
- •Adequate vital functions
- •Patient of child-bearing potential (for female patient: study entry after a menstrual period and a negative pregnancy test) must agree to use medically acceptable methods of contraception during the study and for 4 months after the last intake of study treatment for women and for 6 months after for men.
- •Patient information and signed informed consent form
- •Public or private health insurance coverage
- •Uracilemia < 16 ng/ml
排除标准
- •Patient treated for a cancer other than pancreatic cancer within 5 years before enrolment, with the exception of basal cell carcinoma or in situ cervical cancer
- •Patient with metastasis or with history of metastasis
- •Patient with grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e. congestive heart failure, myocardial infarction within 6 months before baseline)
- •Major comorbidity, active infection (HIV or chronic hepatitis B or C) or uncontrolled diabetes that may preclude the delivery of the treatment
- •Pre-existing neuropathy (Grade ≥ 2), Gilbert's disease or genotype UGT1A1 * 28 / * 28
- •Pregnant woman
- •Fructose intolerance
- •Patients currently treated by warfarin
- •Persons deprived of liberty or under guardianship
- •Psychological condition, family-, sociological- or geographical situation potentially hampering compliance with the study protocol and the follow-up schedule
研究组 & 干预措施
Arm A: Gemcitabine
Gemcitabine 1000 mg/m² IV infusion over 30 minutes on D1 of each week for the 4 weeks of the first cycle (1 cycle = 4 weeks). For the following five cycles, gemcitabine infusion on D1, D8, and D15 of each cycle, followed by 1 week without injection (i.e. in total 4 cycles over 24 weeks; with 19 administrations of Gemcitabine).
干预措施: Gemcitabine (Drug)
Arm B: Folfirinox
Administered once every 14 days for 24 weeks (12 cycles). A cycle equals 14 days with injection on D1 of each cycle. Treatment starts with oxaliplatin (85 mg/m²) administration; IV infusion over 2 hours, followed by the simultaneous administration (using a Y-tubing) of folinic acid 400 mg/m² (racemic) (or 200 mg/m² if L-folinic acid) IV infusion over 2 hours and irinotecan 180 mg/m² IV infusion over 90 minutes. The irinotecan will begin 30 minutes after the start of the folinic acid infusion.
5-Fluoro-uracil (5-FU) IV 2,400 mg/m²/h will be administered over 46 hours after the end of the folinic acid infusion, i.e. 1200 mg/m²/day for the duration of 2 days.
Treatment will be continued for 24 weeks (12 cycles).
干预措施: Folinic Acid (Drug)
Arm B: Folfirinox
Administered once every 14 days for 24 weeks (12 cycles). A cycle equals 14 days with injection on D1 of each cycle. Treatment starts with oxaliplatin (85 mg/m²) administration; IV infusion over 2 hours, followed by the simultaneous administration (using a Y-tubing) of folinic acid 400 mg/m² (racemic) (or 200 mg/m² if L-folinic acid) IV infusion over 2 hours and irinotecan 180 mg/m² IV infusion over 90 minutes. The irinotecan will begin 30 minutes after the start of the folinic acid infusion.
5-Fluoro-uracil (5-FU) IV 2,400 mg/m²/h will be administered over 46 hours after the end of the folinic acid infusion, i.e. 1200 mg/m²/day for the duration of 2 days.
Treatment will be continued for 24 weeks (12 cycles).
干预措施: 5-Fluoro-uracil (Drug)
Arm B: Folfirinox
Administered once every 14 days for 24 weeks (12 cycles). A cycle equals 14 days with injection on D1 of each cycle. Treatment starts with oxaliplatin (85 mg/m²) administration; IV infusion over 2 hours, followed by the simultaneous administration (using a Y-tubing) of folinic acid 400 mg/m² (racemic) (or 200 mg/m² if L-folinic acid) IV infusion over 2 hours and irinotecan 180 mg/m² IV infusion over 90 minutes. The irinotecan will begin 30 minutes after the start of the folinic acid infusion.
5-Fluoro-uracil (5-FU) IV 2,400 mg/m²/h will be administered over 46 hours after the end of the folinic acid infusion, i.e. 1200 mg/m²/day for the duration of 2 days.
Treatment will be continued for 24 weeks (12 cycles).
干预措施: Oxaliplatin (Drug)
Arm B: Folfirinox
Administered once every 14 days for 24 weeks (12 cycles). A cycle equals 14 days with injection on D1 of each cycle. Treatment starts with oxaliplatin (85 mg/m²) administration; IV infusion over 2 hours, followed by the simultaneous administration (using a Y-tubing) of folinic acid 400 mg/m² (racemic) (or 200 mg/m² if L-folinic acid) IV infusion over 2 hours and irinotecan 180 mg/m² IV infusion over 90 minutes. The irinotecan will begin 30 minutes after the start of the folinic acid infusion.
5-Fluoro-uracil (5-FU) IV 2,400 mg/m²/h will be administered over 46 hours after the end of the folinic acid infusion, i.e. 1200 mg/m²/day for the duration of 2 days.
Treatment will be continued for 24 weeks (12 cycles).
干预措施: Irinotecan (Drug)
Arm B: Folfirinox
Administered once every 14 days for 24 weeks (12 cycles). A cycle equals 14 days with injection on D1 of each cycle. Treatment starts with oxaliplatin (85 mg/m²) administration; IV infusion over 2 hours, followed by the simultaneous administration (using a Y-tubing) of folinic acid 400 mg/m² (racemic) (or 200 mg/m² if L-folinic acid) IV infusion over 2 hours and irinotecan 180 mg/m² IV infusion over 90 minutes. The irinotecan will begin 30 minutes after the start of the folinic acid infusion.
5-Fluoro-uracil (5-FU) IV 2,400 mg/m²/h will be administered over 46 hours after the end of the folinic acid infusion, i.e. 1200 mg/m²/day for the duration of 2 days.
Treatment will be continued for 24 weeks (12 cycles).
干预措施: L-folinic (Drug)
结局指标
主要结局
Progression-Free-Survival (PFS)
时间窗: From randomization until disease progression or date of death, assessed up until to 128 weeks
To compare Progression-Free-Survival (PFS) between the two treatment arms
次要结局
- Overall Survival(Until death, assessed up 128 weeks after randomization)
- Percentage of secondarily curative-intent surgery(Until surgery, if applicable, up until 128 weeks after randomization)
- Objective tumour response, disease control and their duration(Until disease progression or date of death, assessed up until 128 weeks after randomization)
- Time to treatment failure(From randomisation to the end of treatment)
- Quality of life questionnaire - Core 30 (QLQ-C30)(assessed up until 128 weeks after randomization)
- Adverse events (NCI-CTCAE version 4.0); observance of chemotherapy(During treatment phase, 24 weeks)
- Composite index for treatment early severe toxicity(First four chemotherapy cycles, 16 weeks)
- Progression-free survival: pattern of failure(Until Disease Progression, assessed uo until 128 weeks after randomization)