Study to Evaluate the Efficacy and Safety of FOLFOX-4 Plus Cetuximab Versus UFOX Plus Cetuximab.
Condition: Previously Untreated Metastatic Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: UFOX + Cetuximab; FOLFOX4 + Cetuximab
Intervention description: Cetuximab infusion (400 mg/m^2 on day 1 of cycle 1 and 250 mg/m^2 at each subsequent day 1, as well as on days 8, 15 and 22)
Oxaliplatin infusion (85mg/m^2) on days 1 and 15 (every 2 weeks)
Oral UFT® (250mg/m^2 tegafur + 560 mg/m^2 uracil in 3 daily doses rounded to the nearest number of whole capsules) on days 1-21
Oral Folinic Acid (90 mg in 3 daily divided doses) on days 1-21; Cetuximab infusion (400 mg/m^2 on day 1 of cycle 1 and 250 mg/m^2 at each subsequent day 1, as well as on days 8, 15 and 22)
Oxaliplatin infusion (85 mg/m^2) on days 1 and 15 (every 2 weeks)
5-FU bolus + infusions (400 mg/m^2) on days 1, 2, 15 and 16
Folinic Acid infusions (200 mg/m^2) on days 1, 2, 15 and 16
Intervention MeSH terms: Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 302.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cancer; Colorectal; Metastatic; Untreated

Summary:

      This is an exploratory study to compare activity and safety in 400 patients with previously
      untreated metastatic carcinoma of the colon treated with UFOX (a combination regimen of UFT®
      (Tegafur plus Uracil), Oxaliplatin, Folinic Acid) plus Cetuximab or FOLFOX-4 (a combination
      regimen of 5 Fluorouracil (5-FU), Oxaliplatin and Folinic Acid) plus Cetuximab)
    

Eligibility criteria:

        Inclusion Criteria

          -  Signed written informed consent

          -  Inpatient or outpatient ≥ 18 years of age

          -  Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum

          -  First occurrence of metastatic disease (not curatively resectable)

          -  Presence of at least one lesion measurable uni dimensionally by computerised
             tomography (CT) scan or magnetic resonance imaging (MRI). (Target lesion(s) must not
             lie within an irradiated area)

          -  Life expectancy of ≥ 3 months

          -  Karnofsky performance status of ≥ 60, at study entry

          -  White blood cell count (WBC) ≥ 3 x 10^9/L, with neutrophils ≥ 1.5 x 10^9/L, platelets
             ≥ 100 x 10^9/L, and hemoglobin ≥ 9 g/dL

          -  Aspartate transaminase and alanine transaminase ≤ 2.5 x Upper Limit of Normal (ULN) (≤
             5 x ULN if liver metastasis are present)

          -  Normal serum creatinine (in case of elevated creatinine, labelled
             ethylenediaminetetraacetic acid clearance ≥ 65 mL/min is acceptable)

          -  Effective contraception for both male and female subjects if the risk of conception
             exists

          -  Tumor biopsy or archived sample available

        Exclusion criteria:

          -  Brain metastasis and/or leptomeningeal disease (known or suspected)

          -  Previous chemotherapy for colorectal cancer except adjuvant treatment with progression
             of disease documented > 6 months after end of adjuvant treatment.

          -  Previous oxaliplatin-based chemotherapy

          -  Surgery (excluding diagnostic biopsy) or irradiation within 4 weeks prior to
             randomization

          -  Concurrent or previous chronic systemic immune therapy, targeted therapy,
             anti-vascular epithelial growth factor (VEGF) therapy, epidermal growth factor
             receptor (EGFR) pathway targeting therapy not indicated in the study protocol

          -  Concurrent hormonal therapy not indicated in the study protocol except for physiologic
             replacement or contraception

          -  Clinically relevant coronary artery disease, history of myocardial infarction in the
             last 12 months, or high risk of uncontrolled arrhythmia

          -  Peripheral neuropathy >grade 1

          -  Known hypersensitivity reaction to any of the components of the treatment.

          -  Any concurrent malignancy other than basal cell cancer of the skin, or pre-invasive
             cancer of the cervix. (Subjects with a previous malignancy but without evidence of
             disease for ≥ 5 years will be allowed to enter the study)

          -  Pregnancy (absence to be confirmed by ß-human chorionic gonadotrophin test) or
             lactation period

          -  Known drug abuse/alcohol abuse

          -  Legal incapacity or limited legal capacity

          -  Medical or psychological condition which in the opinion of the investigator would not
             permit the subject to complete the study or sign meaningful informed consent

          -  Participation in another clinical study within the 30 days before randomization

          -  Significant disease which, in the investigator's opinion, would exclude the subject
             from the study