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Liver and Intrahepatic Bile Duct CarcinomaPhase 2NCT04251715

mFOLFIRINOX Followed by Hepatic Arterial Infusion of Floxuridine and Dexamethasone With Systemic mFOLFIRI for Unresectable Liver-dominant Intrahepatic Cholangiocarcinoma

A Phase 2 study testing Dexamethasone, Floxuridine and Implanted Medical Device in people with Liver and Intrahepatic Bile Duct Carcinoma and Stage III Intrahepatic Cholangiocarcinoma AJCC v8, run by OHSU Knight Cancer Institute at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase II trial studies the efficacy and safety of systemic induction of mFOLFIRINOX, followed by hepatic arterial infusion (HAI) floxuridine-dexamethasone administered concurrently with systemic mFOLFIRI in treating patients with liver-dominant intrahepatic cholangiocarcinoma (ICC) that cannot be removed by… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Dexamethasone, Floxuridine and Implanted Medical Device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
1 siteUnited States
Study dates
28 Apr 2021to 20 Mar 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed intrahepatic cholangiocarcinoma (ICC; also variously reported as peripheral cholangiocarcinoma, cholangiolar carcinoma or cholangiocellular carcinoma) with confirmation of the pathologic diagnosis at Oregon Health \& Science University (OHSU)
  • Surgically unresectable liver-dominant ICC, or multifocal ICC considered surgically unresectable or resection is contraindicated
  • For liver-dominant ICC, disease must comprise < 70% of the liver parenchyma, as defined by computed tomography (CT) liver segmental volumetrics
  • Limited extrahepatic disease
  • Clinical or radiographic evidence of metastatic disease to regional lymph nodes and limited extrahepatic disease to the lungs is permitted at the discretion of the principal investigator (PI)
  • Radiographically measurable hepatic disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria
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  • Disease must be considered technically unresectable at the time of preoperative evaluation or radiographically multifocal as determined by hepatobiliary surgical oncologists
  • Participants should be treatment naive. Those previously treated with systemic chemotherapy (e.g., gemcitabine, cisplatin, or other investigational agents) may be eligible at the discretion of the PI
  • Participants with an Eastern Cooperative Oncology Group (ECOG) 0 or 1 status (Karnofsky >= 60), and can be considered candidates for general anesthesia, abdominal exploration and hepatic artery pump placement
  • Participants with treated chronic hepatitis (e.g., treated hepatitis B virus [HBV], treated hepatitis C virus [HCV]) are eligible, but must be Child-Pugh class A
  • White blood cell (WBC) >= 3000 cells/mm^3
  • Absolute neutrophil count (ANC) >= 1500 cells/mm^3
  • Platelet count >= 100,000/mm^3
  • International normalized ratio (INR) =< 1.5
  • Serum creatinine =< 1.5 x upper limit of normal (ULN) OR creatinine clearance >= 40 ml/min (> 0.675 ml/sec) using Cockcroft-Gault equation
  • Total bilirubin < 1.5 mg/dL
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • 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 and for the duration of study participation
  • Participants must be able to read, understand, and sign informed consent
  • Participants must be willing and able to fully comply with required post-operative visits associated with HAI chemotherapy

Who cannot join

  • Presence of extensive or multifocal metastatic extrahepatic or peritoneal disease. Clinical or radiographic evidence of metastatic disease to regional lymph nodes will be allowed, as will limited pulmonary disease at the discretion of the OHSU PI
  • Prior treatment with floxuridine, oxaliplatin, or irinotecan
  • Prior treatment with hepatic arterial infusion therapy
  • Known to have experienced an allergic reaction or other signs of intolerance to implanted devices
  • Body size that is insufficient to accommodate the physical size of the pump
  • Diagnosis of sclerosing cholangitis
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  • Diagnosis of hepatic encephalopathy
  • Clinical evidence of portal hypertension (ascites, gastroesophageal varices, or portal vein thrombosis) or hepatic venous wedge pressures > 8 mmHg if available
  • History of multiple abdominal operations that would preclude HAI pump placement
  • Active infection
  • Current biliary obstruction requiring placement of endoscopic or transhepatic stents for biliary decompression
  • Presence of aberrant or replaced hepatic arterial anatomy not amenable to placement of a hepatic arterial infusion pump catheter as judged by the operating surgeon
  • History of peripheral neuropathy > grade 1
  • Allergies to iodine contrast medium, that cannot be premedicated with steroids per institutional radiology guidelines (e.g., dexamethasone)
  • Uncontrolled severe coagulation disorders (INR > 1.5 in patients not on warfarin therapy)
  • Pregnant or lactating women
  • History of malignancy other than cholangiocarcinoma within 5 years prior to screening, with the exception of:
  • Malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival [OS] rate > 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, melanoma in situ, localized prostate cancer, ductal carcinoma in situ, or
  • Stage I uterine cancer or a malignancy whose natural history or treatment has, in the opinion of the principal investigator, the potential to interfere with the safety or efficacy assessment of the intervention under investigation
  • Life expectancy =< 12 weeks
  • Inability to comply with study and/or follow-up procedures
  • Emotional or psychiatric problems that would preclude successful participation in the hepatic arterial infusion program as judged by the one of the study investigators, and further corroborated by the mandatory interview and assessment with medical oncology social worker
  • Participants with radiographic evidence of extrahepatic disease
  • Evidence of extrahepatic disease found at laparoscopy during open surgical exploration for HAI pump implantation. Participants with extrahepatic disease found at time of laparoscopy or laparotomy will not undergo surgical placement of HAI pump

Trial locations and contacts

1 site in 1 country.

United States1 site

  • OHSU Knight Cancer Institute

    Portland, Oregon, 97239

Other trials in United States

About this study

Official title: A Phase II Study of Induction Systemic mFOLFIRINOX Followed by Hepatic Arterial Infusion of Floxuridine and Dexamethasone Given Concurrently With Systemic mFOLFIRI as a First-Line Therapy in Patients With Unresectable Liver-Dominant Intrahepatic Cholangiocarcinoma

This phase II trial studies the efficacy and safety of systemic induction of mFOLFIRINOX, followed by hepatic arterial infusion (HAI) floxuridine-dexamethasone administered concurrently with systemic mFOLFIRI in treating patients with liver-dominant intrahepatic cholangiocarcinoma (ICC) that cannot be removed by surgery (unresectable). Drugs used in chemotherapy regimens, such as mFOLFIRINOX and mFOLFIRI (Oxaliplatin, Irinotecan, Fluorouracil, Folinic acid, Floxuridine) work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Delivering chemotherapy via HAI (hepatic arterial infusion) can allow for liver-directed treatment while limiting toxic side effects typically seen with traditional chemotherapy.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Assess the toxicity, safety and tolerability of hepatic arterial infusion (HAI) floxuridine therapy.

II. Evaluate the efficacy of systemic induction of oxaliplatin, leucovorin calcium (folinic acid), irinotecan hydrochloride, and fluorouracil (modified [m] FOLFIRINOX), followed by HAI of floxuridine-dexamethasone (DEX) administered concurrently with systemic irinotecan hydrochloride, leucovorin calcium (folinic acid), and fluorouracil (mFOLFIRI).

SECONDARY OBJECTIVES:

  1. To evaluate tumor response to treatment and participant survival. II. Assess rate of post-operative complications. III. Evaluate serious post-operative complications following surgical placement of the HAI pump.

EXPLORATORY OBJECTIVES:

  1. To assess the radiographic response using diffusion weighted imaging (DWI) as part of an magnetic resonance imaging (MRI) examination.

II. Determine whether, compared to historical controls, induction mFOLFIRINOX combined with integrated HAI of floxuridine-DEX and systemic mFOLFIRI treatment will improve patient quality of life (QoL) including fatigue and depression.

III. Investigate molecular signature associated with intrahepatic cholangiocarcinoma (ICC).

IV. Generate a differential expression pattern of ribonucleic acid (RNA)s (microRNA [miR] and messenger RNA [mRNA]) in patients with ICC derived from tumor samples compared to adjacent normal liver samples as well as lymphatic tissue, blood and bile).

  1. Characterize the changes in the population of circulating hybrid cells (CHCs) pre-, during, and post-treatment.

OUTLINE: This is a phase II, single arm, study that consists of a two-part treatment plan (Treatment Periods 1 and 2) of systemic induction of mFOLFIRINOX, followed by HAI floxuridine-DEX administered concurrently with systemic mFOLFIRI. The first 6 patients enrolled will be part of a safety run-in, after which enrollment could be expanded to additional 24.

After laparoscopic staging, eligible patients will receive a systemic regimen of mFOLFIRINOX with 25% dose reduction of oxaliplatin, irinotecan, and fluorouracil administered every 2-weeks for 4 cycles (8 weeks) (Treatment Period 1). After completing mFOLFIRINOX induction, participants' disease will be re-evaluated by MRI/CT imaging. Only those that achieve disease control based on RECIST criteria (v1.1) will be eligible for HAI therapy via a laparotomy and placement of a HAI pump. (Treatment Period 2).

After completing 2 cycles of HAI treatment with concurrent FOLFIRI, participants will undergo repeat MRI/CT imaging to assess disease response. An image-guided liver biopsy will be performed after completion of the 8 weeks of treatment of HAI floxuridine/dexamethasone combined with systemic mFOLFIRI of Treatment Period 2. Optional extrahepatic biopsies may be collected from participants demonstrating disease progression. Participants with controlled disease (as defined by RECIST criteria) may receive additional cycles of HAI-delivered floxuridine and dexamethasone, along with systemic administration of mFOLFIRI. Completion of QoL questionnaires and interviews will take place at baseline, at the end of treatment period 1 and prior to each HAI treatment cycle, and again at the end of study, and again from the End of Study up to 24 months post study.

Being tested
Dexamethasone, Floxuridine, Implanted Medical Device, Irinotecan, Leucovorin
Medical subject headings
Carcinoma, Hepatocellular, Cholangiocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DexamethasoneDrug

    Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex

    Given intraarterially via HAI pump

  • FloxuridineDrug

    Also called 2''-Deoxy-5-fluorouridine, 5-Fluoro-2''-deoxyuridine, 5-Fluorodeoxyuridine, 5-Fluorouracil deoxyriboside

    Given intraarterially via HAI pump

  • Implanted Medical DeviceDevice

    Also called IMPLANTED

    Implanted hepatic arterial infusion pump by surgical oncology, to deliver HAI therapy

  • IrinotecanDrug

    Given IV

  • LeucovorinDrug

    Also called Folinic acid

    Given IV

  • OxaliplatinDrug

    Also called 1-OHP, Ai Heng, Aiheng, Dacotin

    Given IV

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

Study groups in NCT04251715
Study groupRoleWhat they receive
mFOLFIRINOX, Floxuridine-DEX, mFOLFIRIExperimentalTreatment Period 1 - mFOLFIRINOX for 4 cycles (cycle = 14 days) Cycle 1 * Oxaliplatin 85 mg/m2 intravenously (iv) over 2 hours * Folinic acid 400 mg/m2 iv over 2 hours * Irinotecan 144 mg/m2 iv over 90 minutes * Fluorouracil 2,400 mg/m2 continuous infusion over 46 hours Dosages on Cycle 2, 3, and 4 will be reduced by 25% Treatment Period 2 - HAI delivery of floxuridine + mFOLFIRI for 2 cycles (cycle = 28 days) * Floxuridine-DEX (with heparin and saline) - 0.12 mg/kg/day; via HAI pump, adjusted for weight and flow rate * mFOLFIRI on Day 15 * Irinotecan 150 mg/m2 iv over 30 minutes to 1 hour * Folinic acid 400mg/m2 iv over 30 minutes to 1 hour * 5-FU 1200 mg/m2 continuous infusion over 46 hours
Receives: Drug: Dexamethasone; Drug: Floxuridine; Device: Implanted Medical Device; Drug: Irinotecan; Drug: Leucovorin; Drug: Oxaliplatin; Other: Quality-of-Life Assessment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Frequency of Abnormal Liver Function

    Defined by unacceptable elevation in liver enzymes, or radiographic evidence of biliary sclerosis on computed tomography (CT)/magnetic resonance imaging (MRI) (as measured following the completion of 2 cycles of hepatic arterial infusion [HAI] in Treatment Period 2).

    Measured: Up to 6 months after starting HAI with floxuridine

  2. Disease Control Rate (DCR) - During HAI+SYS

    DCR is defined as the percentage of patients who have achieved complete response (CR), partial response (PR), or stable disease (SD). Measured from beginning of Treatment Period 2 to end of Treatment Period 2 during treatment with HAI + systemic chemotherapy (SYS).

    Measured: Up to 6 months after starting HAI with floxuridine

Secondary outcomes (9)

  1. DCR - Entire Treatment

    Measured from beginning of Treatment Period 1 to end of Treatment Period 2 (i.e., from the beginning of the entire treatment protocol until the end).

    Measured: Up to 2 years

  2. DCR - FOLFIRINOX

    Measured from beginning of Treatment Period 1 to end of Treatment Period 1 (i.e., during the treatment with oxaliplatin, irinotecan, and fluorouracil [FOLFIRINOX] alone).

    Measured: Up to 6 months after starting study intervention

  3. Overall Response Rate (ORR)

    Measured from beginning of Treatment Period 1 to end of Treatment Period 2 (i.e., from the beginning of the entire treatment protocol until the end).

    Measured: Up to 2 years

  4. Percentage of Participants With Progression Free Survival (PFS) at End of Treatment Period 1

    Measured from beginning of Treatment Period 1 to end of Treatment Period 1 (i.e., treatment with FOLFIRINOX alone).

    Measured: Up to 3 months after starting study intervention

  5. Percentage of Participants With Progression Free Survival (PFS) at End of Treatment Period 2

    Measured from beginning of Treatment Period 2 to up to 1 year after the end of Treatment Period 2 (i.e., treatment with HAI Floxuridine + mFOLFIRI).

    Measured: Up to 13.9 months after beginning of Treatment Period 2

  6. Progression Free Survival (PFS)

    Measured from start of study intervention up to 2 years after after starting starting study intervention

    Measured: Up to 24 months after starting study intervention

  7. Overall Survival (OS)

    Measured from start of study intervention up to 3 years after after starting starting study intervention

    Measured: Up to 3 years after starting study intervention

  8. Proportion of Liver Toxicity in Participants Receiving HAI Floxuridine + Dexamethasone Therapy

    Measured: Up to 1 year

  9. Frequency of Serious Post-operative Complications

    Defined as complications occurring within 9 weeks following surgery and >= grade III per the Clavien-Dindo classification system.

    Measured: Up to 9 weeks after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Feb 2020
  2. Study start28 Apr 2021
  3. Primary completion20 Mar 2024
  4. Study completion20 Mar 2024

Why it stopped: change in standard-of-care systemic therapy

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04251715
Sponsor's protocol ID
STUDY00016033
Other IDs
NCI-2020-00477, STUDY00016033, HELIX-1
Status last verified
May 2026
First submitted
30 Jan 2020
Last updated
25 Jun 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes

Publications

  • Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. doi: 10.1097/01.sla.0000133083.54934.ae.

    PubMed 15273542

  • Blair AB, Alobuia WM, Palta M, Raman SS, Levine MH, Benson AB 3rd, D'Angelica MI, Cloyd JM. Locoregional Treatment Options for Locally Advanced Intrahepatic Cholangiocarcinoma. J Natl Compr Canc Netw. 2025 Aug 14;23(9):e257085. doi: 10.6004/jnccn.2025.7085.

    PubMed 40812353

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dexamethasone, Floxuridine and Implanted Medical Device in people with Liver and Intrahepatic Bile Duct Carcinoma and Stage III Intrahepatic Cholangiocarcinoma AJCC v8, run by OHSU Knight Cancer Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency of Abnormal Liver Function (time frame: Up to 6 months after starting HAI with floxuridine). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04251715, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2026.

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