Clinical trial NCT03426371: Epidermal Growth Factor Receptor (EGFR) Antagonist Chimeric Anti-EGFR Monoclonal Antibody Trial
Official title: With or withoutA140 + mFOLFOX6 Treat 1st Line mCRC in RAS Wide Type, Multicenter, Double-blind, Randomized, Controlled Phase III Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Sichuan Kelun Pharmaceutical Research Institute Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-02-08
Enrollment: 570
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: multicenter, double-blind, randomized, controlled phase III trial
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Progression Free Survival (PFS) Time
timeFrame: Time Frame: Baseline up to 128 weeks
Secondary outcomes:
measure: Overall Survival (OS) Time
timeFrame: Time Frame: Baseline up to 258 weeks
measure: Best Overall Response Rate (ORR)
timeFrame: Time Frame: Baseline up to 128 weeks
measure: Time to Treatment Failure (TTF)
timeFrame: Time Frame: Baseline up to 128 weeks
measure: quality of life score
timeFrame: Time Frame: Baseline up to 258 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: 307 Hospital of PLA
state: Beijing
Study officials:
References: