epidermal growth factor receptor (egfr) antagonist chimeric anti-egfr monoclonal antibody trial

Conditions: Metastatic Colorectal Cancer

Summary: 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.


Eligibility criteria:
inclusion criteria: * 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 exclusion criteria: * 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