Open, Randomized, Controlled, Multicenter Phase III Study Comparing CMAB009 Plus FOLFIRI Versus FOLFIRI Alone as First-line Treatment for Epidermal Growth Factor Receptor-expressing, RAS/BRAF Wild-type, Metastatic Colorectal Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 520
- 试验地点
- 2
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
Drugs used against cancer work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as CMAB009, can block tumor growth in different ways. Giving combination chemotherapy together with CMAB009 as first treatment after diagnosis of a metastatic colorectal cancer（first-line treatment）may improve the treatment efficacy. However, it is not yet known whether giving combination chemotherapy together with CMAB009 is more effective than combination chemotherapy alone. This open-label trial investigates the effectiveness of CMAB009 in combination with a standard and effective chemotherapy FOLFIRI（5-Fluorouracil /Folinic acid plus Irinotecan）for RAS/BRAF wild-type, metastatic colorectal cancer in first-line setting, compared to the same chemotherapy alone.
详细描述
Patients will be randomly assign in one of the two groups to either receive the combination chemotherapy alone or with CMAB009 and will then be treated until progression of the disease or unacceptable toxicity occurred. Regular efficacy assessments（every 8 weeks）based on imaging will be performed throughout the study together with regular safety assessments.
After participant discontinuation from the trial, regular updates on further treatments and survival status will be requested from the investigator.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females, Aged ≥18 years and ≤75 years
- •Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum
- •First occurrence of metastatic disease(not curatively resected)
- •RAS/BRAF wild-type status in tumor tissue
- •At least one measurable lesion by computer tomography(CT) or magnetic resonance imaging (MRI)according to RECIST1.1 criteria (not in an irradiated area)
- •Eastern Cooperative Oncology Group(ECOG)performance status of 0 or 1 at trial entry
- •Life expectancy of at least 3 months
- •Medically accepted effective contraception if procreative potential exists(applicable for both male and female subjects until at least 90 days after the last dose of trial treatment)
- •Recovery from relevant toxicity due to previous treatment before trial entry
- •Signed the informed consent form voluntarily
排除标准
- •Radiotherapy or surgery（excluding prior diagnostic biopsy）in the 30 days before trial treatment
- •Hepatic, marrow, liver and renal function as follows:
- •Marrow: white blood cell count <3.0 × 109/L with neutrophils<1.5 × 109/L, platelet count<100×109/L and hemoglobin<90 g/L; Liver function: Total bilirubin >1.5 × upper limit of reference range; Aspartate transaminase (AST) and alanine transaminase (ALT) > 2.5 × upper limit of reference range , or> 5 × upper reference range in subjects with liver metastasis; Renal function: Serum creatinine >1.5 × upper limit of reference range, or creatinine clearance<50 mL/min
- •Previous chemotherapy for CRC adjuvant treatment if terminated <12 months before diagnosis of recurrence or metastatic disease
- •Previous treatment with anti-EGFR monoclonal antibody, epidermal growth factor receptor tyrosine kinase inhibitor, or other EGFR targeted inhibitors(such as cetuximab, Nimotuzumab, or panitumumab)
- •Known hypersensitivity or allergic reactions against any of the components of the trial treatments
- •History of organ allograft, autologous stem cell transplantation, or allogeneic stem cell transplantation
- •Other non-permitted concomitant anti-cancer therapies
- •Known brain metastasis and/or leptomeningeal disease
- •Previous malignancy other than CRC in the last 5 years except basal cell cancer of the skin or preinvasive cancer of the cervix
- •Participation in another clinical trial within the past 30 days
- •Concurrent chronic systemic immune therapy or hormone therapy except physiologic replacement
- •Any unstable systemic disease, such as active infection, uncontrolled hypertension, unstable angina pectoris, angina in the last 3 months, cardiac failure of New York Heart Association classes ≥II, history of myocardial infarction, serious cardiac arrhythmias that require drug treatment, liver, kidney or metabolic disease in the last 6 months
- •Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease
- •severe bone marrow function failure
- •Any disease, metabolic disorders, or physical/laboratory examination suspected, or patients with high risk of complications
- •Known and declared history of human immunodeficiency virus(HIV)infection
- •HBV-DNA >1.0 × 103copy
- •Pregnancy or breastfeeding
- •Alcohol or drug abuse
- •Legal incapacity or limited legal capacity
研究组 & 干预措施
CMAB009 + FOLFIRI
Drug: CMAB009(recombinant chimeric anti-EGFR monoclonal antibody injection), will be administered every 7 days at an initial dose of 400mg/m^2 and 250mg/m^2 for subsequent infusions until progression of disease , withdrawal of consent, or unacceptable toxicity.
Drug: Irinotecan bi-weekly irinotecan infusion of 180mg/m^2 on Day 1. Drug: Folinic Acid infusion 400mg/m^2 of folinic acid in on Day 1. Drug: 5-Fluorouracil bolus 5-Fluorouracil bolus of 400mg/m^2 followed by a 46-48 h continuous infusion of 2400mg/m^2.
every 2 weeks until progression of disease , withdrawal of consent, or unacceptable toxicity.
干预措施: CMAB009 (Drug)
CMAB009 + FOLFIRI
Drug: CMAB009(recombinant chimeric anti-EGFR monoclonal antibody injection), will be administered every 7 days at an initial dose of 400mg/m^2 and 250mg/m^2 for subsequent infusions until progression of disease , withdrawal of consent, or unacceptable toxicity.
Drug: Irinotecan bi-weekly irinotecan infusion of 180mg/m^2 on Day 1. Drug: Folinic Acid infusion 400mg/m^2 of folinic acid in on Day 1. Drug: 5-Fluorouracil bolus 5-Fluorouracil bolus of 400mg/m^2 followed by a 46-48 h continuous infusion of 2400mg/m^2.
every 2 weeks until progression of disease , withdrawal of consent, or unacceptable toxicity.
干预措施: Irinotecan (Drug)
CMAB009 + FOLFIRI
Drug: CMAB009(recombinant chimeric anti-EGFR monoclonal antibody injection), will be administered every 7 days at an initial dose of 400mg/m^2 and 250mg/m^2 for subsequent infusions until progression of disease , withdrawal of consent, or unacceptable toxicity.
Drug: Irinotecan bi-weekly irinotecan infusion of 180mg/m^2 on Day 1. Drug: Folinic Acid infusion 400mg/m^2 of folinic acid in on Day 1. Drug: 5-Fluorouracil bolus 5-Fluorouracil bolus of 400mg/m^2 followed by a 46-48 h continuous infusion of 2400mg/m^2.
every 2 weeks until progression of disease , withdrawal of consent, or unacceptable toxicity.
干预措施: Folinic acid (Drug)
CMAB009 + FOLFIRI
Drug: CMAB009(recombinant chimeric anti-EGFR monoclonal antibody injection), will be administered every 7 days at an initial dose of 400mg/m^2 and 250mg/m^2 for subsequent infusions until progression of disease , withdrawal of consent, or unacceptable toxicity.
Drug: Irinotecan bi-weekly irinotecan infusion of 180mg/m^2 on Day 1. Drug: Folinic Acid infusion 400mg/m^2 of folinic acid in on Day 1. Drug: 5-Fluorouracil bolus 5-Fluorouracil bolus of 400mg/m^2 followed by a 46-48 h continuous infusion of 2400mg/m^2.
every 2 weeks until progression of disease , withdrawal of consent, or unacceptable toxicity.
干预措施: 5-fluorouracil (Drug)
FOLFIRI
FOLFIRI Drug: Irinotecan bi-weekly irinotecan infusion of 180mg/m^2 on Day 1. Drug: Folinic Acid infusion 400mg/m^2 of folinic acid in on Day 1. Drug: 5-Fluorouracil bolus 5-Fluorouracil bolus of 400mg/m^2 followed by a 46-48 h continuous infusion of 2400mg/m^2.
every 2 weeks until progression of disease , withdrawal of consent, or unacceptable toxicity.
干预措施: Irinotecan (Drug)
FOLFIRI
FOLFIRI Drug: Irinotecan bi-weekly irinotecan infusion of 180mg/m^2 on Day 1. Drug: Folinic Acid infusion 400mg/m^2 of folinic acid in on Day 1. Drug: 5-Fluorouracil bolus 5-Fluorouracil bolus of 400mg/m^2 followed by a 46-48 h continuous infusion of 2400mg/m^2.
every 2 weeks until progression of disease , withdrawal of consent, or unacceptable toxicity.
干预措施: Folinic acid (Drug)
FOLFIRI
FOLFIRI Drug: Irinotecan bi-weekly irinotecan infusion of 180mg/m^2 on Day 1. Drug: Folinic Acid infusion 400mg/m^2 of folinic acid in on Day 1. Drug: 5-Fluorouracil bolus 5-Fluorouracil bolus of 400mg/m^2 followed by a 46-48 h continuous infusion of 2400mg/m^2.
every 2 weeks until progression of disease , withdrawal of consent, or unacceptable toxicity.
干预措施: 5-fluorouracil (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Tumor assessments are conducted every 8 weeks after randomization until the end of the study, an average of 1 year.
The PFS duration (in months) is determined by a specially authorized Independent Radiology Review Committee (IRaC) through blinded review of imaging data. It is defined as the time from randomization to the first confirmed progression of disease by imaging or death from any cause within 90 days after the last tumor assessment or randomization, whichever is later (equivalent to 1.5 times the interval between two consecutive tumor assessments).
次要结局
- Quality of Life Assessment Indicators(Assessments are conducted at baseline and subsequent visits every 8 weeks until withdrawal from the study and entry into the follow-up period.)
- Resection Rate of Hepatic Metastasis(From randomization to the end of study)
- Safety Endpoint(From enrollment to the end of study)
- Objective Response Rate (ORR)(Tumor assessments are conducted every 8 weeks after randomization until the end of the study, an average of 1 year.)
- Overall Survival（OS）(From randomization until the end of the study, an average of 1 year.)
- Disease Control Rate (DCR)(Tumor assessments are conducted every 8 weeks after randomization until the end of the study, an average of 1 year.)
- Time to Response (TTR)(Tumor assessments are conducted every 8 weeks after randomization until the end of the study, an average of 1 year.)