Hepatic Arterial Infusion in Treating Patients With Locally Advanced, Non-Metastatic Cholangiocarcinoma

August 8, 2022 updated by: Washington University School of Medicine

Pilot Study of Hepatic Arterial Infusion Therapy in Patients With Unresectable or Borderline Resectable Intrahepatic Cholangiocarcinoma

This pilot clinical trial studies the safety and effectiveness of continuous hepatic arterial infusion (HAI) of floxuridine (FUDR) alone or in combination with other chemotherapeutic drugs in treating patients with locally advanced cholangiocarcinoma that cannot be removed by surgery. HAI is a method to deliver higher concentrations of FUDR more directly to liver tumors and reduces side effects. HAI alone or in combination with oxaliplatin and/or gemcitabine may significantly improve clinical outcomes of patients with locally advanced cholangiocarcinoma.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
27

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patient must have suspected intrahepatic or hilar cholangiocarcinoma with minimal extrahepatic disease. Diagnosis must be histologically or cytologically confirmed for continued treatment on study after pump placement.
  • Patient must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan/MRI
  • Patient must have disease that is unresectable or borderline resectable with < 70% liver involvement by cancer
  • Patient must be >= 18 years old.
  • Patient's Eastern Cooperative Oncology Group (ECOG) performance status must be =< 2 (Karnofsky >= 60%)

  • Patient must have normal organ and marrow function as defined below:

    • Absolute neutrophil count >= 1,500/mcL
    • Platelets >= 75,000/mcL
    • Total bilirubin =< 2 mg/dL
    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 5 X institutional upper limit of normal
    • Creatinine <= institutional upper limit normal
  • Patient must be able to understand and willing to sign a written informed consent document

Exclusion Criteria:

  • Patients must not have had prior treatment with FUDR
  • Patient must not be receiving any other investigational agents
  • Patient must not have a diagnosis of Gilbert's disease
  • Patient must not have a diagnosis of hepatic encephalopathy
  • Patient must not have had prior external beam radiation to the liver
  • Patient must not have a diagnosis of sclerosing cholangitis
  • Patient must not have any 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
  • Patient must not be pregnant or breastfeeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm A (HAI FUDR alone)
  • 14-42 days after surgery for insertion of the HAI pump, floxuridine (FUDR) and dexamethasone plus heparin in normal saline to a total volume of 30 ml will be administered through the HAI pump.
  • This will be repeated on Day 1 of each 28 day cycle. FUDR administration will be a 14-day continuous infusion using the HAI pump.
  • The pump will be emptied and refilled with heparinized normal saline and dexamethasone on Day 15 of each cycle to be infused over the next 14 days.
Drug: Dexamethasone
Other Names:
  • Aeroseb-Dex, Decaderm, Decadron, Decaspray, DM, DXM
Drug: Floxuridine
Other Names:
  • 5-FUDR, FdUrD, floxuridin, fluorodeoxyuridine, fluoruridine deoxyribose, FUdR
Experimental: Arm B (HAI FUDR + gemcitabine)
  • Consists of Cohort B1, B2, and B3. Enrollment to specific cohorts will depend on the number of DLTs in each cohort. Each cohort has a different dose of FUDR and gemcitabine.
  • Gemcitabine IV will be given on Days 1, 8, and 15 of each 28 day cycle in Cohort B1
  • Gemcitabine IV will be given on Days 1 and 15 of each 28 day cycle in Cohort B2 & B3
  • 14-42 days after surgery for insertion of the HAI pump, floxuridine (FUDR) and dexamethasone plus heparin in normal saline to a total volume of 30 ml will be administered through the HAI pump.
  • This will be repeated on Day 1 of each 28 day cycle. FUDR administration will be a 14-day continuous infusion using the HAI pump.
  • The pump will be emptied and refilled with heparinized normal saline and dexamethasone on Day 15 of each cycle to be infused over the next 14 days.
Drug: Gemcitabine
Other Names:
  • dFdC, dFdCyd, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar, LY-188011
Drug: Dexamethasone
Other Names:
  • Aeroseb-Dex, Decaderm, Decadron, Decaspray, DM, DXM
Drug: Floxuridine
Other Names:
  • 5-FUDR, FdUrD, floxuridin, fluorodeoxyuridine, fluoruridine deoxyribose, FUdR
Experimental: Arm C (HAI FUDR + gemcitabine + oxaliplatin)
  • Consists of Cohort C1, C2, C3, and C4. Enrollment to specific cohorts will depend on the number of DLTs in each cohort. Each cohort has a different dose of FUDR, gemcitabine, and oxaliplatin.
  • Gemcitabine IV will be given on Days 1 and 15 of each 28 day cycle.
  • Oxaliplatin IV will be given on Days 1 and 15 of each 28 days cycle.
  • 14-42 days after surgery for insertion of the HAI pump, floxuridine (FUDR) and dexamethasone plus heparin in normal saline to a total volume of 30 ml will be administered through the HAI pump.
  • This will be repeated on Day 1 of each 28 day cycle. FUDR administration will be a 14-day continuous infusion using the HAI pump.
  • The pump will be emptied and refilled with heparinized normal saline and dexamethasone on Day 15 of each cycle to be infused over the next 14 days.
Drug: Gemcitabine
Other Names:
  • dFdC, dFdCyd, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar, LY-188011
Drug: Oxaliplatin
Other Names:
  • 1-OHP, Dacotin, Dacplat, diaminocyclohexane oxalatoplatinum, Eloxatin, L-OHP
Drug: Dexamethasone
Other Names:
  • Aeroseb-Dex, Decaderm, Decadron, Decaspray, DM, DXM
Drug: Floxuridine
Other Names:
  • 5-FUDR, FdUrD, floxuridin, fluorodeoxyuridine, fluoruridine deoxyribose, FUdR

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Dose-limiting toxicities (DLTs)
Time Frame: Completion of 2 cycles of treatment by all patients (approximately 4 years)
Document the frequency of grades 3-5 non-hematologic toxicities (dose-limiting toxicities) associated with the treatment regimen by patient and by type of toxicity for each cohort during the first 2 cycles of treatment
Completion of 2 cycles of treatment by all patients (approximately 4 years)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: Up to 5 years
Up to 5 years
Overall survival
Time Frame: 12 months
12 months
Time to progression (TTP)
Time Frame: 12 months
Describe median time to progression with a 95% confidence interval for each cohort.
12 months
Response rates
Time Frame: 8 weeks

The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started)

Using RECIST 1.1
8 weeks
Number and grade of adverse events
Time Frame: Beginning with pump placement and continuing for 30 days following the last day of study treatment (median length of treatment 3 months)
Determine safety, tolerability and toxicities based on the number and grade of adverse events associated with this regimen.
Beginning with pump placement and continuing for 30 days following the last day of study treatment (median length of treatment 3 months)
Imaging biomarkers of tumor response
Time Frame: Pre-treatment and then every 8 weeks during treatment (median length of treatment 3 months)
Using magnetic resonance diffusion-weighted imaging (DW-MRI) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) before and during the course of treatment with HAI therapy, validate imaging biomarkers of tumor response
Pre-treatment and then every 8 weeks during treatment (median length of treatment 3 months)
Time to progression (TTP)
Time Frame: 24 months
Describe median time to progression with a 95% confidence interval for each cohort.
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Washington University School of Medicine

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: William Chapman, M.D., Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 3, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 8, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 2, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 25, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 30, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 2, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 10, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 8, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 201111068

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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