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

Kelun Pharmaceutical

Status and phase

Enrolling

Phase 3

Conditions

Metastatic Colorectal Cancer

Treatments

Drug: Placebo

Drug: KL-140

Study type

Interventional

Funder types

Industry

Identifiers

NCT03426371

KL140-III-01

Details and patient eligibility

About

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.

Enrollment

570 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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