Hepatic Arterial Infusion Chemotherapy in Patients With Inoperable Colorectal Cancer Liver Metastasis (HAIP-6192)

A Phase II Study of Hepatic Arterial Infusion With Floxuridine and Dexamethasone in Combination With Best Systemic Chemotherapy in Patients With Inoperable Hepatic Metastasis From Colorectal Cancer

The goal of this clinical trial is to assess how many patients with initially inoperable colorectal liver metastasis are able to have a liver surgery after treatment with hepatic artery infusion chemotherapy and standard of care systemic chemotherapy.

Study Overview

• Status: Recruiting
• Conditions: Liver Metastasis Colon Cancer; Liver Metastases From Colorectal Cancer; Colorectal Adenocarcinoma Metastatic in the Liver; Liver Metastases of Colorectal Cancer
• Intervention / Treatment: Drug: Floxuridine (FUDR)

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N3M5
      • Recruiting
      • Sunnybrook Health Sciences Centre
      • Principal Investigator: Paul Karanicolas, MD, PhD
      • Contact: Rachel Roke, BSc (Hons.), MSc; Phone Number: 685391 416-480-6100; Email: rachel.roke@sunnybrook.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. History of histologically confirmed colorectal adenocarcinoma metastatic to the liver with no clinical or radiographic evidence of extrahepatic disease. Patients with resectable or ablatable lung metastasis are eligible.
2. Physically able to tolerate major partial hepatectomy.
3. The primary tumor may be in place at the time of registration if not obstructing the intestinal lumen or significantly bleeding. If present, the primary tumor will be resected at the time of pump placement.
4. Chest, Abdominal and Pelvic CT scan with CT angiogram within 6 weeks prior to registration. (MRI angiogram with contrast of the abdomen may be substituted for CT of the abdomen).
5. The patient must have inoperable liver metastases as agreed upon by any two hepatobiliary surgeons and the assigned radiologist. In the event that two hepatobiliary surgeons cannot agree, a third surgeon will be consulted. Continued discrepancy will result in the patient's case being presented at weekly hepatobiliary conference for consensus opinion. Inoperable metastases are defined as: requiring a resection that leaves less than 2 hepatic segments (not including the caudate lobe) behind with adequate arterial/portal inflow, venous outflow and biliary drainage. * A patient is considered resectable if the procedure includes a minor wedge or thermo-ablation encompassing 10% or less of the volume of the remaining 2 segments.
6. Patient's liver metastases must comprise <70% of the liver parenchyma.
7. Female patients of child-bearing age must undergo a pregnancy test and have a negative result.
8. A patient must have had prior chemotherapy.
9. ECOG PS < 2.
10. Within 14 days of registration: o WBC >3X10E9/L; ANC ≥ 1.5X10E9/L; Platelet count >100X10E9/L; INR < 1.5; HGB ≥ 90 g/L; Estimated creatinine clearance ≥30 ml/min (using Cockcroft and Gault formula); Total serum bilirubin <25.6 umol/L.
11. Age ≥ 18 years.
12. Signed informed consent.
13. Subject's willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
14. Patients with limited/responding lung metastases on Physician's discretion.

Exclusion Criteria:

1. Prior radiation to the liver (prior radiation therapy to the pelvis is acceptable if completed at least 4 weeks prior to registration).
2. Patient may not have received prior treatment with FUDR.
3. Active infection, ascites, hepatic encephalopathy.
4. Active concurrent malignancies, except a patient's potentially resectable colorectal primary.
5. Extrahepatic metastases except for resectable or ablatable lung metastasis.
6. Patient must not have obstruction of GI or GU tract.
7. Female patients who are pregnant or lactating.
8. Patients may not be receiving any other investigational agents.
9. Patients with history of primary CNS tumors, seizures not well-controlled with standard medical therapy, or history of stroke will also be excluded (history of stroke or transient ischemic attack within 6 months prior to Day 1).
10. Serious or non-healing active wound, ulcer, or bone fracture.
11. Chronic daily treatment with aspirin (> 325 mg/d) or nonsteroidal anti- inflammatory medications known to inhibit the platelet function.
12. Presence of bleeding diathesis or coagulopathy.
13. History of serious systemic disease, including myocardial infarction within the last 6 months, uncontrolled hypertension (blood pressure of > 150/100 mmHg on medication), unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e. atrial fibrillation or paroxysmal supraventricular tachycardia are eligible), or peripheral vascular disease (Grade II or greater).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hepatic arterial infusion pump therapy; Hepatic arterial infusion pump therapy with floxuridine (FUDR) and dexamethasone will be administered on Day 1 of each cycle. The pump will be emptied and filled with normal saline on Day 15. Standard of care systemic chemotherapy will be administered on Day 1 and Day 15 as per the treating medical oncologist.	Drug: Floxuridine (FUDR); Floxuridine will be administered at a recommended dose of 0.12 mg/kg/day and adjusted as per participants weight and lab results.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants that undergo liver resection following treatment with FUDR	To assess the rate of conversion to liver resection in patients with initially inoperable hepatic-metastases due to colorectal cancer after treatment with hepatic artery infusion pump therapy and standard of care systemic therapy.	From time of consent to approximately 42 days from last treatment with hepatic artery infusion pump therapy.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to disease progression in all participants	To evaluate time to progression (TTP).	From time of consent to approximately 42 days from last treatment with hepatic artery infusion pump therapy.
Time prior to disease progression in all participants	To evaluate disease-free survival (DFS).	From time of consent to approximately 42 days from last treatment with hepatic artery infusion pump therapy.
Time to intrahepatic disease progression in all participants	To evaluate time to disease progression in liver.	From time of consent to approximately 42 days from last treatment with hepatic artery infusion pump therapy.
Time to death in all participants	Overall survival	From time of consent to approximately 42 days from last treatment with hepatic artery infusion pump therapy.
Number of participants with complete response, partial response, progressive disease, or stable disease as per RECIST Version 1.1	To determine the response rate to systemic chemotherapy and FUDR.	From time of consent to approximately 42 days from last treatment with hepatic artery infusion pump therapy.
Number of participants with grade 3 or higher adverse events as per CTCAE Version 4.03	To evaluate the safety and tolerability of hepatic arterial infusion pump therapy and standard of care systemic therapy.	From time of consent to approximately 42 days from last treatment with hepatic artery infusion pump therapy

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2014
• Primary Completion (Estimated): December 1, 2036
• Study Completion (Estimated): December 1, 2036

Study Registration Dates

• First Submitted: June 23, 2026
• First Submitted That Met QC Criteria: August 11, 2026
• First Posted (Actual): August 14, 2026

Study Record Updates

• Last Update Posted (Actual): August 14, 2026
• Last Update Submitted That Met QC Criteria: August 11, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Deoxyribonucleosides; Deoxyuridine; Uridine; Floxuridine
• Other Study ID Numbers: HAIP-6192

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: To be determined on a case by case basis and appropriate participant consent, research ethics board review, and execution of legal agreements.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes