Irinotecan -Eluting LC Bead-M1 (DEBIRI-M1) for Patients With Liver Metastases From Colorectal Cancer

Inclusion criteria

-Patients with a diagnosis of colorectal cancer with hepatic metastases who have failed or are intolerant to at least one systemic chemotherapy or liver directed therapy.

• The patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at study entry.
• The patient is age 18 years or older.
• The patient has a life expectancy of >12 weeks.
• Patients with liver dominant disease defined as >/=75% tumor body burden confined to the liver
• Less than 60% liver tumor replacement
• At least one month has elapsed since most recent prior cancer therapy with the following exception:

-Chemotherapy (excluding irinotecan based regimens) may continue if there is evidence of hepatic progression on treatment providing there is no change in the therapy in the 1 month prior to DEBIRI-TACE treatment and any immediate chemotherapeutic toxicity that will complicate DEBIRI-TACE is resolved. In this case, the chemotherapy may continue because it is continuing to control the extrahepatic disease.

• The patient has measurable disease that will be directly treated with intrahepatic therapy (as defined by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1).
• Patients with at least one measurable liver metastases> 2 cm.
• Patients with patent main portal vein
• The patient has adequate hematologic function as defined by the following criteria:

-An absolute neutrophil count (ANC) >/= 1500/mL, Hemoglobin >/= 9.5 g/dL, and a Platelet count >/=75,000/mL, INR </=1.3 prior to receiving DEBIRI-TACE.

• The patient has adequate hepatic function, as defined by the following criteria:

-Total bilirubin</= 2.0 mg/dL, Aspartate transaminase (AST) and alanine transaminase (ALT) </= 5 x the upper limit of normal (ULN), Albumin >2.

• The patient has adequate renal function, as defined by the following criteria:

-Serum creatinine</=2.0.

• The patient has a baseline international normalized ratio (INR)<1.5.
• The patient, if a woman of childbearing potential, has a negative pregnancy test.
• The patient is able to give written informed consent.
• The patient is willing and able to comply with study procedures, scheduled visits, and treatment plans.

Exclusion criteria

• The patient has a history of another primary cancer (ie, a primary cancer not associated with the patient's current liver tumor), with the exception of (a) curatively resected nonmelanomatous skin cancer; (b) curatively treated cervical carcinoma in situ; or (c) other primary solid tumor treated with curative intent, no known active disease present, and no treatment administered during the last 3 years prior to enrollment (date of informed consent).
• Any contraindication for hepatic embolization procedures:

• Large shunt as determined by the investigator (pretesting with TcMMA not required)
• Severe atheromatosis
• Hepatofugal blood flow
• Main portal vein occlusion (e.g. thrombus or tumor)
• Any patient eligible for curative treatment (i.e. resection or radiofrequency ablation)
• Patients' whose only measurable disease is within an area of the liver previously subject to radiotherapy
• Contraindications to irinotecan:

• Chronic inflammatory bowel disease and/or bowel obstruction
• History of severe hypersensitivity reactions to irinotecan hydrochloride trihydrate, lactic acid or to any of the excipients of Camptosar
• Severe bone marrow failure
• History of Gilbert Syndrome (specific testing not required)
• Concomitant use with St John's Wort (Hypericum)
• Marco-shunting noted on the hepatic angiogram.
• The patient has untreatable bleeding diathesis.
• The patient has complete main portal vein thrombosis with reversal of flow.
• The patient has evidence of clinically significant peripheral vascular disease.
• The patient has brain metastases
• The patient has clinically significant or symptomatic extrahepatic disease, for example, an uncontrolled intercurrent illness including, but not limited to:

• Ongoing or active infection requiring parenteral antibiotics
• Symptomatic congestive heart failure (class II to IV of the New York Heart Association classification for heart disease)
• Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months
• Uncontrolled hypertension (systolic blood pressure>150 mmHg, diastolic blood pressure>90 mmHg, found on 2 consecutive measurements separated by a 1-week period despite adequate medical support)
• Clinically significant cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or requires treatment [NCI-CTCAE Grade 3] or asymptomatic sustained ventricular tachycardia)
• The patient is pregnant or breast-feeding.
• Psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements
• There is evidence of substance abuse or medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of study results
• The patient is allergic to contrast media that cannot be readily prevented with premedication or managed.
• Other significant medical or surgical condition, or any medication or treatment, that would place the patient at undue risk and that would preclude the safe use of chemoembolization or would interfere with study participation
• The patient has peritoneal disease or ascites (greater than trace on imaging).