The goal of this randomized clinical trial is to investigate induction treatment with Hepatic Arterial Infusion Pump therapy combined with systemic therapy (HAIP-SYST) in chemotherapy-naive patients with unresectable colorectal liver metastases without extrahepatic disease. The main question it aims to answer is if combined HAIP-SYST improves survival compared to induction treatment with systemic therapy alone. Patients in the control arm will receive systemic therapy according to standard of care.
Study procedures experimental arm
* Surgery for pump placement and resection of the primary tumor * Pre- and postoperative imaging (CT-anghiography, 99mTc-MAA scintigraphy) * Induction treatment with hepatic arterial infusion pump therapy with Floxuridine combined with systemic therapy
Study procedures both arms
* Evaluation of resectability status by a National Liver Panel with surgeons and radiologists * Questionnaires for Quality of Life
Age ≥ 18 years.
Histologically confirmed colorectal adenocarcinoma.
Unresectable synchronous CRLM according to a National Liver Panel (CT-scan obtained ≤ 4 weeks prior to registration).
No extrahepatic metastases. Patients with small (≤ 10 mm) extrahepatic lesions that are not clearly suspicious of metastases are eligible.
Prior hepatic radiation, resection, or ablation.
Any malignancy, comorbidity or condition that interferes with the planned study treatment or the prognosis of CRLM, determined by the treating physician.
History of prior malignancy except for the following: (a) malignancy treated with curative intent and with no evidence of active disease present within 3 years prior to inclusion, (b) curatively treated malignancies felt to be at low risk for recurrence by treating physician and MDT, (c) adequately controlled nonmelanomatous skin cancer, (d) adequately treated carcinoma in situ without current evidence of disease.
Obstructive primary tumour requiring emergency surgery, primary tumour necessitating a multivisceral resection/abdominoperineal resection or a rectal tumour requiring preoperative short-course radiotherapy or chemoradiotherapy for local tumour control.
Parallel
Intra arterial infusion Floxuridine (FUDR) combined with systemic therapy
DrugFloxuridine is administered via the hepatic arterial infusion pump directly to the hepatic artery with a continous flowrate for a period of 2 weeks. Intra arterial infusion of FUDR is combined with systemic therapy (FOLFOX/FOLFIRI) intravenously. Administration of FUDR via the chemopump is every 4 weeks and systemic therapy is administered every 2 weeks.
Hepatic arterial infusion pump (HAIP)
DeviceThe HAIP (pump) is implanted during surgery combined with resection of the primary tumor before start of induction treatment with Floxuridine and concomitant systemic therapy
Systemic therapy (standard of care)
DrugPatient included in the control arm will receive systemic therapy according to standard clinical practice. Induction therapy regimens include: CAPOX (3 weekly) or FOLFOX/FOLFIRI/FOLFOXIRI (2weekly) with optional addition of Bevacizumab (2 weekly)
Overall survival
Defined as the time between randomization and the event of death.
Progression-free survival
Defined as the time between randomization and the first event defined as recurrence or death, whichever comes first.
Hepatic progression-free survival
Defined as the time between randomization and the event of progression confined to the liver.
Conversion to resection rate
Defined as conversion surgery with intention of complete local treatment of all CRLM
Complete local treatment rate
R0/1 resection or ablation of all visible CRLM
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