Maintenance Therapy With 5-FU/FA Plus Panitumumab vs. 5-FU/FA Alone After Prior Induction and Re-induction After Progress for 1st-line Treatment of Metastatic Colorectal Cancer

Inclusion criteria

• Signed written informed consent
• Male or female ≥ 18 years of age
• Histologically proven metastatic colorectal cancer
• Molecular testing showing RAS wild-type in colorectal carcinoma cells
• Life expectancy > 12 weeks
• At least one measurable lesion according to RECIST 1.1
• Adequate bone marrow, liver, kidney, organ and metabolic function
• Bone marrow function:

• leukocyte count ≥ 3.0 × 109/L
• ANC ≥ 1.5 × 109/L
• platelet count ≥ 100 × 109/L
• hemoglobin ≥ 9 g/dL or 5.59 mmol/L (may be transfused or treated with erythropoietin to maintain/ exceed this level)
• Hepatic function:

• Total bilirubin ≤ 1.5 × UNL
• ALT and AST ≤ 2.5 × UNL (or ≤ 5 × UNL in presence of liver metastases)
• AP ≤ 5 × UNL
• Renal function:

• Creatinine clearance ≥ 50 mL/min according to Cockcroft-Gault formula or serum creatinine ≤ 1.5 × UNL
• Metabolic function:

• Magnesium ≥ lower limit of normal
• Calcium ≥ lower limit of normal
• ECOG performance status 0 - 1
• Women of child-bearing potential must have a negative pregnancy test

Exclusion criteria

• Previous treatment for colorectal cancer in the metastatic setting
• Previous EGFR-targeting therapy < 6 months after end of adjuvant therapy
• Known brain metastases unless adequately treated (surgery or radiotherapy) with no evidence of progression and neurologically stable off anticonvulsants and steroids
• Chronic inflammatory bowel disease
• Peripheral neuropathy ≥ NCI-CTCAE V 4.03 grade 2
• Other previous malignancies with the exception of a history of previous curatively treated basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix or other curatively treated malignant disease without recurrence after at least 5 years of follow-up
• Significant disease that, in the investigator's opinion, would exclude the patient from the study
• History of cardiac disease; defined as:

• Congestive heart failure > New York Heart Association (NYHA) class 2
• Active coronary artery disease (myocardial infarction more than 6 months prior to start of study treatment is allowed)
• Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted)
• Uncontrolled hypertension (defined as blood pressure ≥ 160 mmHg systolic and/or ≥ 90 mmHg diastolic on medication)
• Patients with interstitial lung disease, e.g., pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan
• Known HIV, hepatitis B or C infection
• Known hypersensitivity reaction to any of the study components
• Radiotherapy, major surgery or any investigational drug 30 days before registration
• Pregnancy or lactation or planning to be pregnant during treatment and within 6 months after the end of treatment
• Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for at least an additional 6 months after the end of treatment
• Known alcohol or drug abuse
• Any condition that is unstable or could jeopardize the safety of the patient and his compliance in the study