Biomarker Directed Treatment in Metastatic Colorectal Cancer

Inclusion criteria

1.1 Inclusion criteria for pre-screening phase:

• Untreated advanced metastatic colorectal cancer patients
• Adequate tissue to evaluate for genotyping (10 x 10µm thick formalin fixed paraffin embedded tissue sections and one corresponding HE stained slide or a FFPE tumor block)

1.2 Inclusion criteria for treatment phase:

Patients must fulfill all criteria listed below prior to enrolment in the study:

• Untreated wild-type KRAS metastatic colorectal cancer
• Previous adjuvant therapy must have been completed > 6 months before therapy initiation on this study
• Age >18 years
• Measureable disease with CT or MRI
• ECOG performance status of 0-2
• Adequate organ function

• Hematologic:

• Absolute neutrophil count > 1,500/µL
• Hemoglobin >9 mg/dl
• Platelet count >100,000 /µl
• Renal:

• Serum creatinine <1.5 x Upper limit of normal (UPN) or estimated clearance > 30 ml/min
• Hepatic:

• Serum bilirubin < 1.5 mg/dl

Exclusion criteria

• Creatinine clearance below 30 ml/min
• Patients with a history of other malignancies within 2 years prior to study entry, except for adequately treated carcinoma in situ of the cervix; basal or squamous cell skin cancer; low grade, early stage localized prostate cancer treated surgically with curative intent; good prognosis DCIS of the breast treated with lumpectomy alone with curative intent.
• Patients with a history of severe cardiac disease; e.g. NYHA Functional Class III or IV heart failure, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, or unstable angina.
• Other known co-morbidity with the potential to dominate survival
• Hypersensitivity with anaphylactic reaction to humanized monoclonal antibodies or any of the applied drugs
• Pregnant or breast feeding women
• Any co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent.