Hepatic arterial infusion pump chemotherapy in patients with unresectable intrahepatic cholangiocarcinoma

• Age ≥ 18 years.

• ECOG performance status 0 or 1 (Appendix A).

• Histologically confirmed diagnosis of intrahepatic cholangiocarcinoma (ICC).

• Unresectable ICC confined to the liver (<70% of the liver involved) with or without limited regional lymph node disease (portal) at initial presentation, as confirmed by HPB surgeons. Regional lymph nodes will be allowed, provided it is potentially amenable to resection. Unresectability confirmed:
o Radiologically
o Or during surgical exploration in patients initially considered candidates for resection

• Patient is able to undergo a laparotomy or minimal-invasive surgery for pump placement.

• Positioning of a catheter for HAIP chemotherapy is technically feasible (see chapter 5) based on a CT with excellent arterial phase. The default site for the catheter insertion is the gastroduodenal artery (GDA). Accessory or aberrant hepatic arteries are no contraindication for catheter placement.

• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 30 days prior to inclusion:
o Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
o White blood cell count (WBC) ≥ 2.5 x 109/L
o Platelets ≥ 100 x 109/L
o Glomerular filtration rate (GFR) ≥ 60 ml/min
o Haemoglobin (HB) ≥ 5.5 mmol/L
o Total bilirubin ≤ 25 μmol/L

• Written informed consent must be given according to ICH/GCP, and national/local regulations.

• Presence of extrahepatic disease at the time of first presentation. Patients with limited (portal) lymph node disease, patients with small (≤ 1 cm) extrahepatic lesions that are too small to characterize are eligible.

• Second primary malignancy, except for adequately treated non-melanoma skin cancer, or other malignancy treated at least 3 years previously without evidence of recurrence or with a life expectancy longer than 5 years.

• Known DPYD deficiency.

• Prior hepatic radiation, ablation, or resection for cholangiocarcinoma.

• Life expectancy of less than 12 weeks.

• Clinical evidence of portal hypertension (ascites, gastroesophageal varices, or portal vein thrombosis). Surgically related ascites is allowed.

• (Partial) portal vein thrombosis.

• Pregnant or lactating women.

• History of psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance for HAIP chemotherapy.

• Serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator.

• Organ allografts requiring immunosuppressive therapy.

• Serious, non-healing wound, ulcer, or bone fracture.

• Chronic treatment with corticosteroids (dose of ≥ 10 mg/day methylprednisolone equivalent excluding inhaled steroids).

• Serious infections (uncontrolled or requiring treatment).

• Participation in another interventional study for ICC with survival as outcome.

• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.