Induction Treatment for Initially Unresectable Colorectal Liver Metastases: Combined Hepatic Arterial Infusion Pump Therapy With Systemic Therapy

NCT06857773 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: M23PIT2023-506194-35-00
• Study Type: interventional
• Target: 306
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Colorectal Neoplasms; Floxuridine; Liver Metastases; Vascular Access Device

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Defined as the time between randomization and the event of death.

  Up to five years after randomization

Secondary Outcomes (11)

• Progression-free survival

  Up to five years after randomization

• Hepatic progression-free survival

  Up to five years after randomization

• Conversion to resection rate

  if CRLM convert to resectable, often at 3-6 months after start induction treatment

• Complete local treatment rate

  if CRLM convert to resectable, often at 3-6 months after start induction treatment

• Objective response rate (ORR)

  During protocol treatment, up to 6 months of induction treatment

Study Arms (2)

A: systemic therapy according to standard of care

ACTIVE COMPARATOR

Patients included in the control arm will receive systemic therapy according to standard of care

Drug: Systemic therapy (standard of care)

B: combined HAIP-therapy and systemic therapy

EXPERIMENTAL

Patients included in the experimental arm undergo surgery for pump placement and resection of the primary tumor. Followed by combined induction treatment with floxuridine via the hepatic arterial infusion pump (1cycle is 4 weeks) and systemic therapy (FOLFOX or FOLFIRI, 1 cycle is 2 weeks)

Drug: Intra arterial infusion Floxuridine (FUDR) combined with systemic therapy; Device: Hepatic arterial infusion pump (HAIP)

Interventions

Intra arterial infusion Floxuridine (FUDR) combined with systemic therapy DRUG

Floxuridine 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.

B: combined HAIP-therapy and systemic therapy

Hepatic arterial infusion pump (HAIP) DEVICE

The HAIP (pump) is implanted during surgery combined with resection of the primary tumor before start of induction treatment with Floxuridine and concomitant systemic therapy

B: combined HAIP-therapy and systemic therapy

Systemic therapy (standard of care) DRUG

Patient 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)

A: systemic therapy according to standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• No previous systemic therapy for colorectal cancer.
• Positioning of a catheter for HAIP chemotherapy is technically feasible based on imaging. The default site for the catheter insertion is the gastroduodenal artery (GDA). Accessory or aberrant hepatic arteries are no contra-indication for catheter implantation. The GDA should have at least one branch to the liver. Accessory or aberrant hepatic arteries should be ligated to allow for cross perfusion to the entire liver through intrahepatic shunts. Patients with celiac trunk stenosis are not eligible. Patients with both a replaced right and replaced left hepatic artery are not eligible.
• ECOG performance status 0 or 1.
• Life expectancy of at least 12 weeks.
• Known mutation status of RAS and BRAFV600E.
• Primary tumour in situ and resectable without neoadjuvant therapy.
• Patient is eligible for surgery.
• Patient is eligible for doublet chemotherapy.
• Laboratory requirements: i.e. adequate bone marrow, liver and renal function (obtained within 15 days prior to registration).
• Hb ≥ 5.5 mmol/L
• absolute neutrophil count (ANC) ≥1.5 x 109/L

You may not qualify if:

• 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.
• 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.
• MMR deficiency.
• DPD-deficiency.
• Pregnant or lactating women.
• 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).
• Known serious infections (uncontrolled or requiring treatment).
• History of psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance for HAIP-SYST or standard systemic therapy.
• 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.
• Underlying liver disease including liver fibrosis and cirrhosis

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead

Study Sites (1)

Antoni van Leeuwenhoek-Netherland Cancer Institute

Amsterdam, 1066CX, Netherlands

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Floxuridine; Standard of Care

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxyuridine; Uridine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Central Study Contacts

Koert FD Kuhlmann, MD PhD

CONTACT

+31205129111; pump@nki.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2024
• First Posted: March 4, 2025
• Study Start: November 21, 2024
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2035
• Last Updated: March 4, 2025

Record last verified: 2025-02

Locations

NL (1)