Intervention: Irinotecan
Trial phase: Phase 1 | Phase 2
ATC code: L01CE02 | L01XX19
SMILES: CCc1c2c(nc3ccc(OC(=O)N4CCC(N5CCCCC5)CC4)cc13)-c1cc3c(c(=O)n1C2)COC(=O)[C@]3(O)CC
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 4
Group description: Irinotecan monotherapy: 250mg/m2 repeated every 3 weeks

Irinotecan: Irinotecan monotherapy: 250mg/m2 repeated every 3 weeks
Eligibility criteria:
Inclusion Criteria:

Patients with confirmed diagnosis of stage IV colorectal cancer with unresectable liver metastases (primary tumor may be present)
Patients with at least one measurable liver metastases, with size > 1cm (RECIST criteria)
Patients with liver dominant disease defined as ≥50% tumor body burden confined to the liver
Patients with patent main portal vein
Performance status ≤ 2 ECOG
Life expectancy > 6 months
Aged ≥18 years
Patient has failed (discontinued for progression or toxicity) one prior line of chemotherapy for metastatic disease, preferably oxaliplatin-based (e.g. FOLFOX, CAPOX). Note that substitutions of oral versus IV 5-FU formulations, changes in 5-FU schedules, or discontinuations/re-starting of the same chemotherapy drugs will not be considered as separate lines of therapy, nor will the addition of "biologics" such as bevacizumab, cetuximab, or panitumumab
Patient has no previous treatment with irinotecan
At least 4 weeks since last administration of last chemotherapy and /or radiotherapy
Hematologic function: ANC ≥ 1.5 x 109/L, platelets ≥75 x10-9/L, INR <1.5 (patients on therapeutic anticoagulants are not eligible)
Adequate liver function as measured by: Total bilirubin ≤ 2.0mg/dl, ALT, AST ≤5 times ULN, albumin ≥2.5g/dl,
Adequate renal function (creatinine ≤ 2.0mg/dl)
Women of child bearing potential and fertile men are required to use effective contraception (negative serum βHCG/urine test for women of child-bearing age)
Signed, written informed consent

Exclusion Criteria:

Patient eligible for curative treatment (i.e. resection or radiofrequency ablation). Note: resectability is defined as a single tumor <5cm with adequate liver function defined: Total bilirubin ≤ 2.0mg/dl, ALT, AST ≤5 times ULN, albumin ≥2.5g/dl
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)
Active bacterial, viral or fungal infection within 72 hours of study entry
Women who are pregnant or breast feeding
Previous irinotecan based therapy for metastatic disease
Patients' whose only measurable disease is within an area of the liver previously subject to radiotherapy
Allergy to contrast media that cannot be managed with standard care (e.g. steroids)
Presence of another malignancy with the exception of cervical carcinoma in situ and stage I basal or squamous carcinoma of the skin
Contraindicated for MRI or CT
Patients previously treated with transarterial embolization (with or without chemotherapy)
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)
Other significant medical or surgical condition, or any medication or treatment, that would place the patient at undue risk, that would preclude the safe use of chemoembolization or would interfere with study participation