Included patients must fulfil the following criteria
1. Primary histology: verified adenocarcinoma in colon or rectum
2. Liver metastases
a. Not possible or feasible to resect at time of inclusion.
b. Resection will require 10 % or more response in index lesions.
c. And one of the following:
- Insufficient response on current line chemotherapy and in need of next line systemic chemotherapy or major change of active agents as judget by treating oncologist.
- Treatment stopped due to toxicity, and hence in need of next line systemic chemotherapy.
a. Patients must have received at least one line of systemic chemotherapy at time of inclusion in the study. Planned for next line chemotherapy.
b. If patients have commenced next line chemotherapy, randomization can only be allowed prior to first evaluation on next line chemotherapy regimen.
4. The patient
a. Good performance status, ECOG 0 or 1.
b. Satisfactory blood tests: Hb >9 g/dl, neutrophiles >1.0 (after any G-CSF), TRC >75, Bilirubin<1.5 x upper normal level, ASAT, ALAT<5 x upper normal level, Creatinine <1.25 x upper normal level. Albumin above lower normal level.
5. Signed informed consent and expected cooperation of the patients for treatment and follow up must be obtained and documented according to GCP, and national/local regulations.
Any of the following criteria will exclude participation in the trial:
1. Arterial anatomy not suited for HAI pump-line insertion.
2. A primary tumour in situ that is either a
a. Rectal tumour scheduled for radiation therapy with fractionation 2 Gy x 25, or
b. A right-sided or transverse colonic tumour
3. Previous or current bone or CNS metastatic disease.
4. Patients with known intolerance or allergy to any ingredient of the IMP to be used as standard therapy for that patient
5. Breastfeeding women
6. Patients with a psychiatric condition that makes participation in the trial impossible or unethical
7. Patients in a poor nutritional state, those with depressed bone marrow function or those with potentially serious infections must be excluded.
8. Any other reason why, in the opinion of the investigators, the patient should not participate.
Stratification of Excalibur 2:
For patients eligible for Excalibur 2, randomization will be in stratum:
2a for patients with none of the following features
2b for patients with any of the following features
1. Non-curable pulmonary disease
2. Non-hilar, non-regional lymph node metastases
3. Limited and resectable peritoneal disease