A Trial to Compare Oxaliplatin, Folinic Acid (FA) and 5-Fluorouracil (5FU) Combination Chemotherapy (FOLFOX-4) With or Without Cetuximab in the 1st Line Treatment of Metastatic Colorectal Cancer (mCRC) in Chinese Rat Sarcoma Viral Oncogene Homolog (RAS) Wild-type Patients
Condition: Metastatic Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: Cetuximab; Oxaliplatin; Folinic Acid; 5Fluorouracil
Intervention description: Cetuximab was 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 cetuximab.; 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.; 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.; 5-FU as a bolus of 400 mg/m^2/day intravenously over 2-4 minutes followed by 600 mg/m^2/day infusion over 22 hours on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.
Intervention MeSH terms: Leucovorin; Folic Acid; Fluorouracil; Oxaliplatin; Cetuximab; Levoleucovorin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 553.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic colorectal cancer; RAS wild type; Cetuximab; First line treatment; First occurrence of metastatic colorectal cancer in Chinese subjects with RAS wildtype; status

Summary:

      The purpose of this study was to assess whether the progression free survival (PFS) time with
      FOLFOX-4 plus cetuximab is longer than that with FOLFOX-4 alone as first-line treatment for
      mCRC in Chinese subjects with RAS wild-type tumors.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed written informed consent (first and second)

          -  Chinese with Chinese citizenship

          -  Male or female subjects greater than or equal to (>=) 18 years of age

          -  Medically accepted effective contraception if procreative potential exists (applicable
             for both male and female subjects until at least 90 days after the last dose of trial
             treatment)

          -  Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum

          -  First occurrence of metastatic disease (not curatively resectable) RAS wild-type
             status in tumor tissue

          -  At least one measurable lesion by computer tomography (CT) or magnetic resonance
             imaging (MRI) according to RECIST (not in an irradiated area)

          -  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
             >= 100 × 10x9/L and hemoglobin >= 6.21 mmol/L (10 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

          -  Recovery from relevant toxicity due to previous treatment before trial entry

        Exclusion Criteria:

          -  Previous chemotherapy for CRC except adjuvant treatment if terminated > 9 months
             (oxaliplatin-based chemotherapy) or > 6 months (non-oxaliplatin-based chemotherapy)
             before the start of treatment in this trial

          -  Radiotherapy or surgery (excluding prior diagnostic biopsy) in the 30 days before
             trial treatment

          -  Previous treatment with monoclonal antibody therapy, vascular endothelial growth
             factor (VEGF) pathway-targeting therapy, epidermal growth factor receptor (EGFR)
             pathway-targeting therapy, or other signal transduction inhibitors

          -  History of organ allograft, autologous stem cell transplantation, or allogeneic stem
             cell transplantation

          -  Renal replacement therapy

          -  Intake of any investigational medication within 30 days before trial entry

          -  Concurrent chronic systemic immune therapy or hormone therapy except physiologic
             replacement

          -  Granulocyte colony stimulating factor (G-CSF) or granulocyte macrophage colony
             stimulating factor (GM-CSF) within 3 weeks of trial entry (these growth factors may be
             used during the trial thereafter)

          -  Other non-permitted concomitant anticancer therapies

          -  Known brain metastasis and/or leptomeningeal disease. Subjects with neurological
             symptoms should undergo a CT scan/MRI of the brain to exclude brain metastasis

          -  Previous malignancy other than CRC in the last 5 years except basal cell cancer of the
             skin or preinvasive cancer of the cervix

          -  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

          -  Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease

          -  Active clinically serious infections (> grade 2 National Cancer Institute-Common
             Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0), including active
             tuberculosis

          -  Known and declared history of human immunodeficiency virus (HIV) infection or chronic
             hepatitis B or C

          -  Peripheral neuropathy > grade 1

          -  Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family
             members who suffer(ed) from such

          -  Uncontrolled diabetes mellitus, pulmonary fibrosis, acute pulmonary disorder,
             interstitial pneumonia, or liver failure

          -  Known hypersensitivity or allergic reactions against any of the components of the
             trial treatments

          -  Pregnancy (absence to be confirmed by serum β-human chorionic gonadotropin test) or
             breastfeeding

          -  Ongoing alcohol or drug abuse

          -  Presence of a medical or psychological condition that would not permit the subject to
             complete the trial or sign informed consent

          -  Participation in another clinical trial within the past 30 days

          -  Other significant disease that in the investigator's opinion should exclude the
             subject from the trial

          -  Legal incapacity or limited legal capacity