Observational Study on Second Line Treatment of Liver Metastases With DEBIRI and Cetuximab

This is an observational study and the treatment is related to the experiences and economical availability of each center.

Primary objective: To collect data on time to progression (local and/or distant progression) after administration of Dc-Beads microspheres preloaded with Irinotecan 200 mgr via hepatic intra-arterial locoregional delivery (TACE) in/without association with standard weekly therapy with Cetuximab.

Secondary objectives: To collect data on tolerability of treatment and improvement of quality of life (Edmonton Symptom Assessment System (ESAS))

Treatment under observation :

Program A ( for all patients)

Day +1:

Lobar Infusion (lobe with dominant disease) of Irinotecan 100 mg preloaded into 2 ml of 70-150 µm M1 microspheres.

Second lobar infusion of Irinotecan 100 mg preloaded into 2 ml of 70-150 µm M1 microspheres can be administered at the same time contralaterally or in a further TACE.

Day +30: The above procedure is repeated. Day +90: In case of response, a third administration following the above procedures will be repeated

Program B ( for Centers in which Cetuximab is available) 5.2 Cetuximab administered as per standard scheme: Day -15: loading dose with 400 mg/mq i.v. over a 2-hour period Day +21 and subsequent weekly administrations: 250 mg/mq i.v. over a one hour period.

It is pointed out that administration of Cetuximab will be continued following the timeline of the first infusion relative to the intra-arterial administration.

Evaluation of response

Response must be assessed by repeating the following examinations at Day 30, Day 90 and Day 120 after start of treatment:

Chest-abdomen CAT scan with and without contrast medium (refer to Section 4). Evaluation will be based on the Response Evaluation Criteria In Solid Tumors (RECIST) cancer markers (CEA, Carbohydrate Antigen (CA) 19.9)

Assessment of quality of life The Edmonton Symptom Assessment System (ESAS) is used to monitor health conditions and quality of life.

The questionnaire must be filled in by the patient unaided by family members or by health care personnel, over a period of about 15 minutes. Assessment of quality of life will be performed during the baseline visit and at Day 30, Day 60 and Day 120 from start of treatment.

It is important for the questionnaire to be completed by the patient before undergoing the physical examination, in other words before discussing with the physician about any examinations which might give an indication of the favorable or unfavorable course of the disease. In providing the questionnaire to the patient, the physician will explain how to complete it without discussing the contents of the questions, and once the patient has completed the questionnaire, the physician will check that all questions have been answered.

Inclusion criteria

• Unresectable hepatic metastases from colorectal carcinoma (CRC-LM)
• Progression of disease after first line therapy containing Irinotecan completed at least one month previously
• Performance status (PS) 0-2
• Biochemistry parameters within normal limits (ALT and gamma glutamyl transpeptidase not exceeding three times the upper limit of normal, total bilirubin not exceeding 2.5 mg/ml)
• Adequate information and subsequent written informed consent
• Life expectancy > 3 months
• Patients K-RAS wild type

Exclusion criteria

• Extension of disease greater than 50% of the parenchymal liver (confirmed by CAT scan or MRI)
• Brain metastases
• Severe and confirmed vascular diseases
• Other concomitant malignancies except for cutaneous basal cell carcinoma or carcinoma in situ of the uterine cervix
• Evidence of significant diseases such as uncontrolled diabetes, congestive heart failure, chronic renal insufficiency (CRI)
• Known hypersensitivity reactions towards components of the study drugs
• Pregnant or breastfeeding women or women of childbearing potential not making use of effective contraceptives
• Family, psychological, social or geographical circumstances preventing the patient from undergoing follow-up and from complying with protocol procedures
• Patients K-RAS mutant