Optimal Control of Liver Metastases From Colorectal Cancer With Cetuximab and Hepatic Artery Infusion of Chemotherapy (OPTILIV)

• Histologically or cytologically confirmed carcinoma of the colon and/or rectum with evidence of liver metastases (new confirmation of metastatic disease is required in case the time interval from last histological diagnosis to enrolment exceeds 3 years).
• Patient with wild type (WT) KRAS tumor status

• Patient whose liver metastases are considered to be non resectable with curative intent in medico-surgical staff meeting. In particular patients with at least one of the following criteria, which prevent complete local treatment of liver metastasis with surgery alone or surgery plus radiofrequency ablation because:

  • less than 30% estimated residual liver after resection
  • disease in contact with liver main vessels
  • documented progressive disease on imaging documents or doubling of serum levels of carcino-embryonic antigen (CEA) or CA19.9 over the past 90 days or less
• Patient with up to three resectable extrahepatic nodules of <= 10 mm
• One, two or three prior chemotherapy lines for colorectal cancer.
• Written informed consent.
• Age >=18 years.
• Patient must be able to comply with the protocol.
• Life expectancy of at least 3 months.
• At least one measurable metastatic liver lesion (as per RECIST criteria).
• World Health Organization performance status of 0 or 1.
• Adequate hematological function: absolute neutrophil count (ANC) >=1.0 x 10^9/L; platelets >=75 x 10^9/L, hemoglobin (Hb) >=8.5 g/dL.
• International normalized ratio (INR) <=1.5 and activated partial thromboplastin time (aPTT) <=1.5 x upper limit of normal (ULN) within 7 days prior to starting study treatment, in the absence of anticoagulant therapy.
• Liver function: serum bilirubin <=1.5 x ULN; alkaline phosphatase and transaminases <5 x ULN (liver metastases).
• Serum creatinine <= 1.5 x ULN.
• Fertile women and men of childbearing potential (<2 years after last menstruation in women) must use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile).

Exclusion Criteria:

• Patient whose primary tumor or metastasis displays mutation of K-Ras (codon 12 and/or 13).
• Unresectable extrahepatic diseases.
• More than three resectable extrahepatic nodules.
• Size of extra hepatic nodules > 1 cm
• Prior HAI of the 3 drugs.
• More than 2 prior surgical attempts for metastatic disease
• Prior radiotherapy for metastatic disease
• Known documented intolerance or hypersensitivity to any of the drugs used.
• Sensory neuropathy grade 3 (National Cancer Institute-Common Terminology Criteria for Adverse Events -NCI-CTCAE, Version 3.0).
• Past or current history (within the last 2 years prior to treatment start) of malignancy other than colorectal cancer (patients with curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible).
• Serious, non healing wound, ulcer, or bone fracture.
• Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that puts the patient at high risk for treatment-related complications.
• Pregnancy or lactation
• Fertile women (< 2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception.

Prior systemic administration of cetuximab or other anti-EGFR agent is not an exclusion criterion.