With or withoutA140 + mFOLFOX6 Treat 1st Line mCRC in RAS Wide Type, Multicenter, Double-blind, Randomized, Controlled Phase III Trial
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Progression Free Survival (PFS) Time
研究概览
简要总结
The study is an double blind, randomized, multicenter phase 3 trial. The efficacy analyses are based on 570 Chinese patients with RAS wt mCRC treated with mFOLFOX-6 ± cetuximab. Study treatment continues until disease progression or unacceptable toxicity (ie, not for a fixed number of courses). The primary endpoint of the study is progression-free survival (PFS) time according to RECIST 1.0; key secondary endpoints include overall survival (OS) time, overall response rate (ORR), and safety/tolerability.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Signed written informed consent
- •Male or female subjects， 18-75 years of age
- •Medically accepted effective contraception if procreative potential exists
- •Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum
- •RAS wild-type and BRAF-V600E wild-type status in tumor tissue
- •At least one measurable lesion by computer tomography (CT) or magnetic resonance imaging (MRI) according to RECIST
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at trial entry
- •Life expectancy of at least 12 weeks
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at trial entry
- •White blood cell count >= 3 × 10x9/L with neutrophils >= 1.5 × 10x9/L, platelet count >=75 × 10x9/L and hemoglobin >= 8 g/dL； 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；Serum creatinine <= 1.5 × upper limit of reference range
排除标准
- •Known hypersensitivity or allergic reactions against any of the components of the trial treatments
- •Radiotherapy or surgery (excluding prior diagnostic biopsy) in the 28 days before trial treatment
- •Known brain metastasis and/or leptomeningeal disease. Subjects with neurological symptoms should undergo a CT scan/MRI of the brain to exclude brain metastasis
- •Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease，except the patient with fistulation or stenting
- •Active clinically serious infections (> grade 2 National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0), including active tuberculosis
- •Uncontrolled diabetes mellitus, pulmonary fibrosis, acute pulmonary disorder, interstitial pneumonia, or liver failure
- •Clinically significant cardiovascular disease, e.g. cardiac failure of New York Heart Association classes III-IV, uncontrolled coronary artery disease, cardiomyopathy, uncontrolled arrhythmia, uncontrolled hypertension, or history of myocardial infarction in the last 5 years, or left ventricular ejection fraction below the institutional range of normal on a baseline multiple gated acquisition scan or echocardiogram
- •Renal replacement therapy
- •Peripheral neuropathy > grade 1
- •History of organ allograft, autologous stem cell transplantation, or allogeneic stem cell transplantation
- •Previous malignancy other than CRC in the last 5 years except basal cell cancer of the skin or preinvasive cancer of the cervix
- •Known and declared history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
- •Known severe coagulation disorders
- •Previous chemotherapy for CRC except adjuvant treatment if terminated > 12 months (oxaliplatin-based chemotherapy) or > 6 months (non-oxaliplatin-based chemotherapy) before the start of treatment in this trial
- •Previous treatment with anti-EGFR monoclonal antibody therapy
- •Other non-permitted concomitant anticancer therapies, chronic systemic immune therapy or hormone therapy
- •Granulocyte colony stimulating factor (G-CSF) or granulocyte macrophage colony stimulating factor (GM-CSF) within 3 weeks of trial entry，blood transfusion，or blood components transfusion
- •Pregnancy (absence to be confirmed by serum β-human chorionic gonadotropin test) or breastfeeding
- •Ongoing alcohol or drug abuse
- •Known neurological or psychiatric diseases
- •Participation in another clinical trial within the past 4 weeks
- •Legal incapacity or limited legal capacity
- •Other significant disease that in the investigator's opinion should exclude the subject from the trial
研究组 & 干预措施
Experimental
All eligible subjects will receive KL-140 in combination with mFOLFOX-6 chemotherapy regimen.
干预措施: KL-140 (Drug)
Placebo Comparator
All eligible subjects will receive Placebo in combination with mFOLFOX-6 chemotherapy regimen.
干预措施: Placebo (Drug)
结局指标
主要结局
Progression Free Survival (PFS) Time
时间窗: Time Frame: Baseline up to 128 weeks
PFS was defined as the duration (in months) from randomization until the first progressive disease (PD) observation as assessed by the investigators according to Response Evaluation Criteria for Solid Tumors (RECIST) version 1.0, or death due to any cause when death occurred within 90 days of randomization or the last tumor assessment, whichever was later. PD was defined as at least a 20% increase in the sum of longest diameter (LD) of the target lesions, taking as references the smallest sum LD since the treatment started (including baseline), or appearance of one or more new lesions, and/or unequivocal progression of existing non-target lesions.
次要结局
- Overall Survival (OS) Time(Time Frame: Baseline up to 258 weeks)
- Best Overall Response Rate (ORR)(Time Frame: Baseline up to 128 weeks)
- Time to Treatment Failure (TTF)(Time Frame: Baseline up to 128 weeks)
- quality of life score(Time Frame: Baseline up to 258 weeks)