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

NCT ID: NCT03426371

Last Updated: 2018-02-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 570 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-28
• Study Completion Date: 2023-12-31

Brief 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.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Experimental

All eligible subjects will receive KL-140 in combination with mFOLFOX-6 chemotherapy regimen.

Group Type: EXPERIMENTAL

KL-140

Intervention Type: DRUG

KL-140 will be administered every 7 days at an initial dose of 400 milligram per square meter (mg/m^2) at 5 milligram per minute (mg/min) and 250 mg/m^2 at 10 mg/min for subsequent infusions until progression of disease, withdrawal of consent, or unacceptable toxicity to KL-140.

Drug: Oxaliplatin Oxaliplatin 85 mg/m^2 infusion over 120 minutes on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

Drug: Folinic Acid FA 200 mg/m^2 infusion over 120 minutes on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

Drug: 5Fluorouracil 5-FU as a bolus of 400 mg/m^2/day intravenously followed by 2400 mg/m^2/day infusion over 48 hours on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

Placebo Comparator

All eligible subjects will receive Placebo in combination with mFOLFOX-6 chemotherapy regimen.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be administered every 7 days at an initial dose of 400 milligram per square meter (mg/m^2) at 5 milligram per minute (mg/min) and 250 mg/m^2 at 10 mg/min for subsequent infusions until progression of disease, withdrawal of consent, or unacceptable toxicity Drug: Oxaliplatin Oxaliplatin 85 mg/m^2 infusion over 120 minutes on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

Drug: Folinic Acid FA 200 mg/m^2 infusion over 120 minutes on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

Drug: 5Fluorouracil 5-FU as a bolus of 400 mg/m^2/day intravenously followed by 2400 mg/m^2/day infusion over 48 hours on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

Interventions

KL-140

KL-140 will be administered every 7 days at an initial dose of 400 milligram per square meter (mg/m^2) at 5 milligram per minute (mg/min) and 250 mg/m^2 at 10 mg/min for subsequent infusions until progression of disease, withdrawal of consent, or unacceptable toxicity to KL-140.

Drug: Oxaliplatin Oxaliplatin 85 mg/m^2 infusion over 120 minutes on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

Drug: Folinic Acid FA 200 mg/m^2 infusion over 120 minutes on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

Drug: 5Fluorouracil 5-FU as a bolus of 400 mg/m^2/day intravenously followed by 2400 mg/m^2/day infusion over 48 hours on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

Intervention Type: DRUG

Placebo

Placebo will be administered every 7 days at an initial dose of 400 milligram per square meter (mg/m^2) at 5 milligram per minute (mg/min) and 250 mg/m^2 at 10 mg/min for subsequent infusions until progression of disease, withdrawal of consent, or unacceptable toxicity Drug: Oxaliplatin Oxaliplatin 85 mg/m^2 infusion over 120 minutes on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

Drug: Folinic Acid FA 200 mg/m^2 infusion over 120 minutes on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

Drug: 5Fluorouracil 5-FU as a bolus of 400 mg/m^2/day intravenously followed by 2400 mg/m^2/day infusion over 48 hours on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sichuan Kelun Pharmaceutical Research Institute Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

307 Hospital of PLA

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Facility Contacts

Jianming Xu

Role: primary

Hjc1126@sina.com

010-56943977

Other Identifiers

KL140-III-01

Identifier Type: -

Identifier Source: org_study_id