Hepatic Artery Infusion Pump Chemotherapy With Floxuridine and Dexamethasone in Combination With Systemic Chemotherapy for Patients With Colorectal Cancer Metastatic to the Liver

NCT03366155 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 18002418-C-0024
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Many people with colorectal cancer get liver metastases. Standard treatment for this is a combination of chemotherapy drugs. Directing the chemotherapy to the liver may be effective. A device that does this a pump that delivers drugs over 2 weeks at constant rate into the hepatic artery. The person's body temperature causes the drug to flow from the pump. Researchers want to see if this helps people with colorectal metastases to the liver. Objective: To study the effectiveness of a hepatic artery infusion pump at treating colorectal metastases to the liver. Eligibility: Adults at least 18 years old with colorectal metastases to the liver Design: Participants will be screened with: Medical history Physical exam Heart, blood, and urine tests Scans Participants will stay in the hospital a few days. A small plastic tube (catheter) will be inserted in an artery into the liver. The catheter will be attached to the pump. That will lie under the skin on the abdomen. It will be small and participants will be able to feel it. Participants will get treatment in 28-day cycles. Every Day 1, they will have physical exam, symptom review, and blood tests. Every 2 weeks, they will come to the clinic to get chemotherapy by a catheter or port. Every 12 weeks, they will have a scan. Tissue samples may be taken during the study. When they finish the drug, participants may have the pump removed. They will repeat the Day 1 tests. They will be called every 6 months to see how they are doing.

Conditions

Colorectal Cancer; Liver Metastases; Colorectal Adenocarcinoma; Colorectal Cancer With Hepatic Metastases; Colorectal Carcinoma

Keywords

Unresectable Liver Tumor; Response Rates; Progression-Free Survival; Patient Survival

Outcome Measures

Primary Outcomes (3)

• Response Rate (RR) Reported With an 80% Confidence Interval

  Response rate is defined as the number of participants who experience a partial response (PR) or complete response (CR) using the study treatment was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) and reported with an 80% confidence interval. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Complete Response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.

  6 months

• Response Rate (RR) Reported With a 95% Confidence Interval

  Response rate is defined as the percentage of participants who experience a partial response (PR) or complete response (CR) using the study treatment determined by dividing the number of responders by the total evaluable participants. RR was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and reported with an 95% confidence interval. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Complete Response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.

  6 months

• Number of Grade 1, 2, 3, 4, and/or 5 Serious and/or Non-serious Adverse Events Reported With Type and Frequency

  Safety was determined by grade 1, 2, 3, 4, and/or 5 serious and/or non-serious adverse events with type and frequency assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.

  30 days

Secondary Outcomes (3)

• Overall Survival

  Date of Hepatic Artery Infusion Pump (HAIP) insertion through death or study completion, up to 63.1 months

• Intra-Hepatic Progression-free Survival (PFS)

  Date of hepatic artery infusion pump (HAIP) insertion through either the date of first hepatic progression or study completion, up to 63.1 months

• Extra-hepatic Progression-free Survival (PFS)

  Date of hepatic artery infusion pump (HAIP) insertion through either the date of first extra-hepatic progression or study completion, up to 63.1 months

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  Adverse Events were monitored/assessed from the time of operation through 30 days after the participant was taken off treatment, up to 27.7 months

Study Arms (1)

1/ Arm 1: Hepatic Artery Infusion Pump (HAIP) Chemotherapy + Systemic Chemotherapy

EXPERIMENTAL

HAIP chemotherapy + Systemic chemotherapy

Device: Codman 3000 constant flow pump catheter; Drug: Panitumumab; Drug: FUDR-Dex; Drug: Oxaliplatin; Drug: 5FU; Drug: Irinotecan; Procedure: HAIP installation; Drug: cetuximab; Device: Medtronic SynchroMed II Pump; Drug: Floxuridine; Drug: Dexamethasone; Diagnostic Test: EKG; Diagnostic Test: CT C/A/P; Diagnostic Test: CT Angiogram (abdomen); Procedure: Tumor and normal liver biopsy; Drug: Leucovorin

Interventions

Codman 3000 constant flow pump catheter DEVICE

Implanted Medtronic SynchroMed II Pump with codman 3000 Constant Flow Pump Catheter

1/ Arm 1: Hepatic Artery Infusion Pump (HAIP) Chemotherapy + Systemic Chemotherapy

Panitumumab DRUG

6 mg/kg, intravenous (IV)

Also known as: Vectibix

1/ Arm 1: Hepatic Artery Infusion Pump (HAIP) Chemotherapy + Systemic Chemotherapy

FUDR-Dex DRUG

Hepatic Artery Infusion Pump (HAIP) will be filled with mixture of Floxuridine and Dexamethasone. Pump will perfuse drugs to liver for 14 days. Floxuridine (0.12 mg/kg X pump volume X pump flow rate), Dexamethasone (1 mg/day X pump volume (30) X pump flow rate)

Also known as: Floxuridine and Dexamethasone

1/ Arm 1: Hepatic Artery Infusion Pump (HAIP) Chemotherapy + Systemic Chemotherapy

Floxuridine DRUG

Floxuridine 0.12 mg/kg X pump volume X pump flow rate

Also known as: 5-fluorodeoxyuridine

1/ Arm 1: Hepatic Artery Infusion Pump (HAIP) Chemotherapy + Systemic Chemotherapy

Dexamethasone DRUG

1 mg/day X pump volume (30) X pump flow rate

Also known as: Decadron

1/ Arm 1: Hepatic Artery Infusion Pump (HAIP) Chemotherapy + Systemic Chemotherapy

EKG DIAGNOSTIC_TEST

Screening and baseline.

Also known as: Electrocardiogram

1/ Arm 1: Hepatic Artery Infusion Pump (HAIP) Chemotherapy + Systemic Chemotherapy

CT C/A/P DIAGNOSTIC_TEST

Screening, baseline and Cycle 1. One cycle is 28 (+/- 2 days).

Also known as: Computed tomography chest, abdomen, pelvis

1/ Arm 1: Hepatic Artery Infusion Pump (HAIP) Chemotherapy + Systemic Chemotherapy

CT Angiogram (abdomen) DIAGNOSTIC_TEST

Screening

Also known as: Computed tomography angiogram (abdomen)

1/ Arm 1: Hepatic Artery Infusion Pump (HAIP) Chemotherapy + Systemic Chemotherapy

Tumor and normal liver biopsy PROCEDURE

For research: During surgery to install pump, time of progression per principal investigator discretion if safe, and end of treatment.

Also known as: Tumor and normal liver bx

1/ Arm 1: Hepatic Artery Infusion Pump (HAIP) Chemotherapy + Systemic Chemotherapy

Leucovorin DRUG

400 mg/m\^2, intravenous (IV), (Day15, Day1)

Also known as: folinic acid

1/ Arm 1: Hepatic Artery Infusion Pump (HAIP) Chemotherapy + Systemic Chemotherapy

Oxaliplatin DRUG

85 mg/m\^2, intravenous (IV)

Also known as: Eloxatin

1/ Arm 1: Hepatic Artery Infusion Pump (HAIP) Chemotherapy + Systemic Chemotherapy

5FU DRUG

2000 mg/m\^2, intravenous (IV) 46-hour infusion of 5-Fluorouracil + 400 mg/m\^2, IV of Leucovorin

Also known as: 5-Fluorouracil

1/ Arm 1: Hepatic Artery Infusion Pump (HAIP) Chemotherapy + Systemic Chemotherapy

Irinotecan DRUG

150 mg/m\^2, intravenous (IV)

Also known as: Camptosar, Onivyde

1/ Arm 1: Hepatic Artery Infusion Pump (HAIP) Chemotherapy + Systemic Chemotherapy

HAIP installation PROCEDURE

Hepatic Artery Infusion (HAI) pump installation

Also known as: Hepatic Artery Infusion Pump (HAIP) installation

1/ Arm 1: Hepatic Artery Infusion Pump (HAIP) Chemotherapy + Systemic Chemotherapy

cetuximab DRUG

500 mg/m\^2, intravenous (IV)

Also known as: Erbitux

1/ Arm 1: Hepatic Artery Infusion Pump (HAIP) Chemotherapy + Systemic Chemotherapy

Medtronic SynchroMed II Pump DEVICE

Implanted Medtronic SynchroMed II Pump with Codman 3000 Constant Flow Pump Catheter

1/ Arm 1: Hepatic Artery Infusion Pump (HAIP) Chemotherapy + Systemic Chemotherapy

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed diagnosis of colorectal adenocarcinoma.
• Patients must have measurable liver metastatic disease.
• Patients must have progressed on, been intolerant of or have residual disease after oxaliplatin- or irinotecan-containing, fluorouracil-based, chemotherapeutic regimen.
• Age greater than or equal to 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1
• Patients must have adequate organ and marrow function as defined below:
• leukocytes \> 3,000/mcL
• absolute neutrophil count \> 1,500/mcL
• platelets \> 90,000/mcL
• total bilirubin \< 1.5 X institutional upper limit of normal
• Aspartate aminotransferase (AST) Serum glutamic oxaloacetic transaminase (SGOT)/Alanine transaminase (ALT) Serum glutamic-pyruvic transaminase (SGPT) \< 2.5 X institutional upper limit of normal
• creatinine within normal institutional limits OR estimated glomerular filtration rate (eGFR) within normal as predicted by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation \> 60 mL/min/1.73 m\^2.
• The hepatic artery infusion pump chemotherapy has potential teratogenic and/or abortifacient effects. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and after completion of study treatment : 3 months after the last study drug for men; 6 months after the last study drug for women. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• Arterial anatomy on computed tomography (CT) angiogram amenable to placement of the Hepatic Artery Infusion Pump (HAIP).
• Ability of subject to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Patients with liver metastases amenable to resection to No Evidence of Disease (NED) in one stage.
• Patients who are receiving any other investigational agents.
• Patients with incontrovertible radiographic evidence of disease outside of the colon/rectum (primary) and liver given unlikelihood of benefit from liver-directed therapy.
• Patients who have undergone extra-hepatic metastasectomy and have a documented disease-free interval less than or equal to 4 months.
• Microsatellite Instability (MSI)-high patients who need to be treated with check-point inhibitors
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. This also includes any condition, including the presence of laboratory abnormalities, which in the opinion of the Principal Investigator places the subject at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study.
• Active concurrent malignancies within the last five years other than colorectal primary except basal cell skin carcinoma and thyroid carcinoma.
• Prior radiation to liver.
• Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects of the HAIP chemotherapy. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with HAIP, breast-feeding should be discontinued if the mother is treated. These potential risks may also apply to other agents used in this study. Lactating women must-not breastfeed during study treatment and until at least 7 days after the final dose of study drug(s).
• Patients with active Hepatitis B or C infection because of the potential for increased liver toxicity given the damaging effects of the virus.
• History of allergic reactions attributed to compounds of similar chemical composition to floxuridine (FUDR) or heparin.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Ammori JB, Kemeny NE, Fong Y, Cercek A, Dematteo RP, Allen PJ, Kingham TP, Gonen M, Paty PB, Jarnagin WR, D'Angelica MI. Conversion to complete resection and/or ablation using hepatic artery infusional chemotherapy in patients with unresectable liver metastases from colorectal cancer: a decade of experience at a single institution. Ann Surg Oncol. 2013 Sep;20(9):2901-7. doi: 10.1245/s10434-013-3009-3. Epub 2013 Jun 15.

  PMID: 23771246 BACKGROUND

• D'Angelica MI, Correa-Gallego C, Paty PB, Cercek A, Gewirtz AN, Chou JF, Capanu M, Kingham TP, Fong Y, DeMatteo RP, Allen PJ, Jarnagin WR, Kemeny N. Phase II trial of hepatic artery infusional and systemic chemotherapy for patients with unresectable hepatic metastases from colorectal cancer: conversion to resection and long-term outcomes. Ann Surg. 2015 Feb;261(2):353-60. doi: 10.1097/SLA.0000000000000614.

  PMID: 24646562 BACKGROUND

• Cercek A, D'Angelica M, Power D, Capanu M, Gewirtz A, Patel D, Allen P, Fong Y, DeMatteo RP, Jarnagin WR, Kemeny NE. Floxuridine hepatic arterial infusion associated biliary toxicity is increased by concurrent administration of systemic bevacizumab. Ann Surg Oncol. 2014 Feb;21(2):479-86. doi: 10.1245/s10434-013-3275-0. Epub 2013 Oct 24.

  PMID: 24154839 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Panitumumab; Floxuridine; Dexamethasone; Oxaliplatin; Fluorouracil; Irinotecan; irinotecan sucrosofate; Cetuximab; Calcium Dobesilate; Electrocardiography; Tumor Burden; Leucovorin

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxyuridine; Uridine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Camptothecin; Alkaloids; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis; Body Weights and Measures; Anthropometry; Investigative Techniques; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Results Point of Contact

• Title: Dr. Jonathan M. Hernandez
• Organization: National Cancer Institute

jonathan.hernandez@nih.gov

240-760-6072

Study Officials

• Jonathan M Hernandez, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 7, 2017
• First Posted: December 8, 2017
• Study Start: June 24, 2019
• Primary Completion: November 13, 2025
• Study Completion: November 13, 2025
• Last Updated: August 28, 2026
• Results First Posted: August 28, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

Locations

US (1)