Hepatic arterial infusion pump chemotherapy combined with systemic therapy versus systemic therapy alone as induction treatment for initially unresectable colorectal liver metastases: a study protocol of the randomised controlled trial – PUMP-IT RCT

BACKGROUND: In patients with colorectal cancer liver metastases (CRLM), resection of the primary tumour and local treatment of liver metastases may offer a chance of cure or long-term survival. Most patients however present with unresectable CRLM. Hepatic arterial infusion pump (HAIP) therapy with floxuridine (FUDR) combined with systemic therapy (SYST) could enhance conversion to resectable CRLM, reduce recurrences and therefore, probably prolong survival. The aim of this trial is to investigate whether intensifying induction treatment with HAIP-SYST prolongs survival in chemotherapy-naive patients with initially unresectable CRLM as compared to systemic therapy alone. METHODS: This multicentre, phase 3 randomised controlled trial will be conducted in 20 Dutch liver centres and 306 patients will be included. Eligible participants are chemotherapy-naive patients with synchronous unresectable CRLM without extrahepatic disease and with suitable hepatic arterial anatomy to allow for potential pump placement. Unresectability is assessed by a liver expert panel of radiologists and surgeons based on predefined criteria. Patients randomised to the control arm receive induction systemic therapy according to standard clinical practice. Patients in the experimental arm undergo surgery for pump placement and resection of the primary tumour before start of HAIP-SYST. Treatment response and conversion to local treatment of CRLM is evaluated by the expert panel every 8-9 weeks during induction treatment. Primary endpoint is overall survival (OS). Secondary endpoints include progression-free survival (PFS), hepatic PFS, conversion-to-resection rates, R0/R1 resection rates, radiological and pathological response, surgical complications, toxicity, quality of life and cost-effectiveness. DISCUSSION: The PUMP-IT RCT is the first prospective randomised trial to investigate HAIP-SYST as first line treatment for initially unresectable CRLM. This Dutch multicentre trial is open for accrual as of November 2024. TRIAL REGISTRATION: PUMP-IT RCT is registered at EU Clinical Trials (EU CT): 2023-506,194-35-00, at CCMO: NL86326.041.24 and at ClinicalTrials.gov: NCT06857773, August 1, 2024. PROTOCOL VERSION: version 3.1, 29- 04-2026.