A Multinational, Randomized, Phase III Study of FOLFIRI With/Without Bevacizumab Versus Irinotecan With/Without Bevacizumab As Second-line Therapy in Patients With Metastatic Colorectal Cancer
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 280
- 试验地点
- 1
- 主要终点
- Overall survival
研究概览
简要总结
The primary purpose of this study is to determine the non-inferiority of overall survival FOLFIRI with or without Bevacizumab compared with Irinotecan (CPT-11) with or without Bevacizumab as Second-line therapy in Patient with Metastatic Colorectal Cancer.
详细描述
Primary endpoint: Progression-free survival (PFS)； Secondary endpoints: Overall survival (OS), Time to treatment failure (TTF), Overall response rate (ORR), Disease Control Rate (DCR), Safety.
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-confirmed inoperable colorectal adenocarcinoma excluding vermiform appendix cancer and anal canal cancer.
- •Age ≥18 years at the time of informed consent
- •ECOG performance status (PS) of 0-2
- •Written informed consent prior to study-specific screening procedures
- •Life expectancy of at least 90 days
- •Withdrawal from first-line chemotherapy (regardless of containing molecular-targeted drugs) for metastatic colorectal cancer due to intolerable toxicity or progressive disease, or relapse within 180 days after the last dose of adjuvant chemotherapy.
- •Adequate organ function according to following laboratory values obtained within 14 days before enrolment (excluding patients who received blood transfusions or hematopoietic growth factors within 14 days before the laboratory test) Neutrophil count: ≥1500/mm3 Platelet count: ≥10.0 x 104/mm3 Hemoglobin: ≥9.0 g/dL Total bilirubin: ≤1.5 mg/dL AST, ALT: ≤100 IU/L (≤200 IU/I if liver metastases present) Serum creatinine: ≤1.5 mg/dL
排除标准
- •History of other malignancy with a disease-free interval <5 years (other than curatively treated cutaneous basal cell carcinoma, curatively treated carcinoma in situ of the cervix, and gastroenterological cancer confirmed to be cured by endoscopic mucosal resection)
- •With massive pleural effusion or ascites requiring intervention
- •Radiological evidence of brain tumor or brain metastases
- •Active infection including hepatitis
- •Any of the following complication:
- •i) Gastrointestinal bleeding or gastrointestinal obstruction (including paralytic ileus) ii) Symptomatic heart disease (including unstable angina, myocardial infarction, and heart failure) iii) Interstitial pneumonia or pulmonary fibrosis iv) Uncontrolled diabetes mellitus v) Uncontrolled diarrhea (that interferes with daily activities despite adequate therapy)
- •Any of the following medical history:
- •Myocardial infarction: History of one episode within one year before enrollment or two or more lifetime episodes i) Serious hypersensitivity to any of the study drugs ii) History of adverse reaction to fluoropyrimidines suggesting dihydropyrimidine dehydrogenase (DPD) deficiency
- •Previous treatment with irinotecan hydrochloride
- •Current treatment with atazanavir sulfate
- •Previous treatment with tegafur, gimeracil, and oteracil potassium within seven days before enrollment
- •Pregnant or lactating females, and males and females unwilling to use contraception
- •Requires continuous treatment with systemic steroids
- •Psychiatric disability that would preclude study compliance
- •Otherwise determined by the investigator to be unsuitable for participation in the study
- •Concurrent gastrointestinal perforation or history of gastrointestinal perforation with 1 year before enrollment
- •History of pulmonary hemorrhage/hemoptysis ≥ Grade 2 (defined as bright red blood of at least 2.5mL) within 1 month prior to enrollment.
- •History of laparotomy, thoracotomy, or intestinal resection within 28 days before enrollment
- •Unhealed wound (except suture wounds from implantation of a central venous port), gastrointestinal ulcer, or traumatic fracture
- •Current or recent (within 1 year) thromboembolism or cerebrovascular disease
- •Currently receiving or requires anticoagulation therapy (> 325 mg/day of aspirin)
- •Bleeding diathesis, coagulopathy, or coagulation factor abnormality (INR ≥1.5 within 14 days before enrollment)
- •Uncontrolled hypertension
- •Urine dipstick for proteinuria >+2
研究组 & 干预措施
CPT-11 +/- Bevacizumab
Bevacizumab 5 mg/kg IV 90-30 min Day 1; CPT-11 180 mg/m2 IV 90 min Day 1
干预措施: Bevacizumab (Biological)
FOLFIRI +/- Bevacizumab
Bevacizumab 5 mg/kg IV 90-30 min Day 1; CPT-11 180 mg/m2 IV 90 min Day 1; l-LV (dl-LV) 200 mg/m2 (400 mg/m2) IV 120 min Day 1; 5-FU - bolus 400 mg/m2 IV bolus Day 1; 5-FU - infusional 2400 mg/m2 IV continuous (46 hours) Day 1 - 3
干预措施: CPT-11 (Drug)
FOLFIRI +/- Bevacizumab
Bevacizumab 5 mg/kg IV 90-30 min Day 1; CPT-11 180 mg/m2 IV 90 min Day 1; l-LV (dl-LV) 200 mg/m2 (400 mg/m2) IV 120 min Day 1; 5-FU - bolus 400 mg/m2 IV bolus Day 1; 5-FU - infusional 2400 mg/m2 IV continuous (46 hours) Day 1 - 3
干预措施: l-LV (dl-LV) (Drug)
FOLFIRI +/- Bevacizumab
Bevacizumab 5 mg/kg IV 90-30 min Day 1; CPT-11 180 mg/m2 IV 90 min Day 1; l-LV (dl-LV) 200 mg/m2 (400 mg/m2) IV 120 min Day 1; 5-FU - bolus 400 mg/m2 IV bolus Day 1; 5-FU - infusional 2400 mg/m2 IV continuous (46 hours) Day 1 - 3
干预措施: Bevacizumab (Biological)
FOLFIRI +/- Bevacizumab
Bevacizumab 5 mg/kg IV 90-30 min Day 1; CPT-11 180 mg/m2 IV 90 min Day 1; l-LV (dl-LV) 200 mg/m2 (400 mg/m2) IV 120 min Day 1; 5-FU - bolus 400 mg/m2 IV bolus Day 1; 5-FU - infusional 2400 mg/m2 IV continuous (46 hours) Day 1 - 3
干预措施: 5-FU Bolus (Drug)
FOLFIRI +/- Bevacizumab
Bevacizumab 5 mg/kg IV 90-30 min Day 1; CPT-11 180 mg/m2 IV 90 min Day 1; l-LV (dl-LV) 200 mg/m2 (400 mg/m2) IV 120 min Day 1; 5-FU - bolus 400 mg/m2 IV bolus Day 1; 5-FU - infusional 2400 mg/m2 IV continuous (46 hours) Day 1 - 3
干预措施: 5-FU Infusion (Drug)
CPT-11 +/- Bevacizumab
Bevacizumab 5 mg/kg IV 90-30 min Day 1; CPT-11 180 mg/m2 IV 90 min Day 1
干预措施: CPT-11 (Drug)
结局指标
主要结局
Overall survival
时间窗: Assessed until 1.5 years after the last patient enrolment
Time from the date of enrollment to death from any cause
次要结局
- Overall Response Rate (ORR)(Assessed at 6, 12 week and thereafter every 8 weeks, from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks)
- Incidence of Adverse Events (Adverse Reactions)(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks)
- Progression-free survival (PFS)(Assessed until 1.5 years after the last patient enrolment)
- Time to treatment failure (TTF)(Assessed until 1.5 years after the last patient enrolment)
- Disease Control Rate (DCR)(Assessed at 6, 12 week and thereafter every 8 weeks, from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks)
研究者
Rui-hua Xu, MD, PhD
Professor and President
Sun Yat-sen University