Phase II Trial of FOLFOXIRI + Bevacizumab in Patients With Untreated Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 45
- 试验地点
- 7
- 主要终点
- Response rate (RR) by response evaluation criteria in solid tumors (RECIST v1.1)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of fluorouracil (5-FU), levofolinate calcium (l-LV), oxaliplatin (L-OHP) and irinotecan hydrochloride hydrate (CPT-11) (FOLFOXIRI) plus bevacizumab in untreated metastatic colorectal cancer patients who harbor Uridine diphosphate (UDP)-glucuronosyl transferase 1A1 (UGT1A1) *1/*1, *1/*6 or *1/*28.
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
- 20 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed adenocarcinoma of the colon or rectum.
- •Unresectable or recurrent colorectal cancer patient.
- •One or more measurable lesion in RECIST ver.1.1 criteria.
- •No prior chemotherapy, immunotherapy, and radiotherapy.
- •Life expectancy at least 3 months.
- •Patients who harbor UGT1A1*1/*1, *1/*6 or *1/*
- •The Eastern Cooperative Oncology Group (ECOG) performance status of =<
- •Vital organ functions (listed below) are preserved within 14 days prior to entry.
- •White blood cell count (WBC): >= 3,000 per cubic millimeter Neu: >= 1,500 per cubic millimeter Platelet count (PLT): >= 100,000 per cubic millimeter Aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT): <= 100 IU/L, <= 150 IU/L in cases with liver metastasis T-bil: <= 1.5 mg/dL Serum creatinine: <= 1.50 mg/dL Proteinuria: <= 1+ Prothrombin time-international normalized ratio (PT-INR): < 1.5
- •Written informed consent.
排除标准
- •Vermiform appendix cancer and anal canal cancer.
- •Administration of blood products/ granulocyte-colony stimulating factor (G-CSF), and blood transfusion within 14 days prior to enrollment.
- •Synchronous multiple malignancy or metachronous multiple malignancy less than 5 years disease free interval.
- •Hepatitis B virus antigen (HBs-Ag)(+), or hepatitis C virus antibody (HCV-Ab)(+).
- •History of severe allergy.
- •Sensory alteration or paresthesia interfering with function.
- •Prior radiotherapy for ilium and abdomen.
- •Infectious disease.
- •Uncontrolled diarrhea.
- •Ileus or bowel obstruction.
- •Interstitial lung disease or pulmonary fibrosis.
- •Malignant coelomic fluid required drainage.
- •Administration of atazanavir sulfate.
- •Heart disease to be clinically problem.
- •Major surgical procedure or intestinal resection within 28 days prior to enrollment or colostomy within 14 days prior to enrollment.
- •Known brain metastasis or strongly suspected of brain metastasis.
- •History of a thromboembolic disease.
- •Receiving anti-platelet drugs.
- •Poorly controlled gastrointestinal ulcer.
- •History of intestinal perforation within the past 12 months.
- •Poorly controlled hypertension.
- •Poorly controlled diabetes mellitus.
- •Severe mental disorders.
- •Women who are pregnant or nursing, men and women who wish to conceive a child or with no intention to contraception.
- •Any other cases who are regarded as inadequate for study enrollment by investigators.
研究组 & 干预措施
Treatment Arm
Patients receive FOLFOXIRI plus bevacizumab [oxaliplatin (L-OHP): 85 mg/sq.m., irinotecan hydrochloride hydrate (CPT-11): 165 mg/sq.m., continuous intravenous infusion of fluorouracil (CIV 5-FU): 3,200 mg/sq.m., Levofolinate calcium (l-LV): 200 mg/sq.m., bevacizumab: 5 mg/kg]. The treatment will be repeated every 2 weeks, for up to 12 cycles, unless the disease progression, unacceptable toxicity, tumor resection or consent withdrawal.
干预措施: Oxaliplatin (L-OHP) (Drug)
Treatment Arm
Patients receive FOLFOXIRI plus bevacizumab [oxaliplatin (L-OHP): 85 mg/sq.m., irinotecan hydrochloride hydrate (CPT-11): 165 mg/sq.m., continuous intravenous infusion of fluorouracil (CIV 5-FU): 3,200 mg/sq.m., Levofolinate calcium (l-LV): 200 mg/sq.m., bevacizumab: 5 mg/kg]. The treatment will be repeated every 2 weeks, for up to 12 cycles, unless the disease progression, unacceptable toxicity, tumor resection or consent withdrawal.
干预措施: Irinotecan hydrochloride hydrate (CPT-11) (Drug)
Treatment Arm
Patients receive FOLFOXIRI plus bevacizumab [oxaliplatin (L-OHP): 85 mg/sq.m., irinotecan hydrochloride hydrate (CPT-11): 165 mg/sq.m., continuous intravenous infusion of fluorouracil (CIV 5-FU): 3,200 mg/sq.m., Levofolinate calcium (l-LV): 200 mg/sq.m., bevacizumab: 5 mg/kg]. The treatment will be repeated every 2 weeks, for up to 12 cycles, unless the disease progression, unacceptable toxicity, tumor resection or consent withdrawal.
干预措施: Continuous intravenous infusion of fluorouracil (CIV 5-FU) (Drug)
Treatment Arm
Patients receive FOLFOXIRI plus bevacizumab [oxaliplatin (L-OHP): 85 mg/sq.m., irinotecan hydrochloride hydrate (CPT-11): 165 mg/sq.m., continuous intravenous infusion of fluorouracil (CIV 5-FU): 3,200 mg/sq.m., Levofolinate calcium (l-LV): 200 mg/sq.m., bevacizumab: 5 mg/kg]. The treatment will be repeated every 2 weeks, for up to 12 cycles, unless the disease progression, unacceptable toxicity, tumor resection or consent withdrawal.
干预措施: Levofolinate calcium (l-LV) (Drug)
Treatment Arm
Patients receive FOLFOXIRI plus bevacizumab [oxaliplatin (L-OHP): 85 mg/sq.m., irinotecan hydrochloride hydrate (CPT-11): 165 mg/sq.m., continuous intravenous infusion of fluorouracil (CIV 5-FU): 3,200 mg/sq.m., Levofolinate calcium (l-LV): 200 mg/sq.m., bevacizumab: 5 mg/kg]. The treatment will be repeated every 2 weeks, for up to 12 cycles, unless the disease progression, unacceptable toxicity, tumor resection or consent withdrawal.
干预措施: Bevacizumab (Bmab) (Drug)
结局指标
主要结局
Response rate (RR) by response evaluation criteria in solid tumors (RECIST v1.1)
时间窗: Up to 18 months
RR will be calculated as the ratio of the number of eligible patients who experienced a confirmed Complete response(CR) or Partial response(PR) by RECIST v1.1.
次要结局
- Overall survival (OS)(Up to 3 years)
- Incidence of adverse events(Up to 3 years)
- Progression-free survival (PFS)(Up to 3 years)
- Time to treatment failure (TTF)(Up to 18 months)
- R0 resection rate(Up to 18 months)
- Relative dose intensity (RDI)(Up to 18 months)