Epidermal Growth Factor Receptor (EGFR) Antagonist Chimeric Anti-EGFR Monoclonal Antibody Trial

• Status: Recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sichuan Kelun Pharmaceutical Research Institute Co., Ltd.
• Treatments: Cetuximab

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