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

This study is currently recruiting participants.
Verified June 2017 by Washington University School of Medicine
Sponsor:
ClinicalTrials.gov Identifier:
NCT01525069
First Posted: February 2, 2012
Last Update Posted: July 2, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Washington University School of Medicine
  Purpose
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.

Condition Intervention Phase
Cholangiocarcinoma Liver Neoplasms Drug: Floxuridine Drug: Dexamethasone Drug: Gemcitabine Drug: Oxaliplatin Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of Hepatic Arterial Infusion Therapy in Patients With Unresectable or Borderline Resectable Intrahepatic Cholangiocarcinoma

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • Time to progression (TTP) [ Time Frame: 12 months ]
    Describe median time to progression with a 95% confidence interval for each cohort.

  • 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


  • Overall survival [ Time Frame: 12 months ]
  • 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.

  • 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

  • Overall survival [ Time Frame: 24 months ]
  • Time to progression (TTP) [ Time Frame: 24 months ]
    Describe median time to progression with a 95% confidence interval for each cohort.


Estimated Enrollment: 18
Actual Study Start Date: April 3, 2012
Estimated Study Completion Date: December 31, 2019
Estimated Primary Completion Date: December 31, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: Floxuridine
Other Name: 5-FUDR, FdUrD, floxuridin, fluorodeoxyuridine, fluoruridine deoxyribose, FUdR
Drug: Dexamethasone
Other Name: Aeroseb-Dex, Decaderm, Decadron, Decaspray, DM, DXM
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: Floxuridine
Other Name: 5-FUDR, FdUrD, floxuridin, fluorodeoxyuridine, fluoruridine deoxyribose, FUdR
Drug: Dexamethasone
Other Name: Aeroseb-Dex, Decaderm, Decadron, Decaspray, DM, DXM
Drug: Gemcitabine
Other Name: dFdC, dFdCyd, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar, LY-188011
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: Floxuridine
Other Name: 5-FUDR, FdUrD, floxuridin, fluorodeoxyuridine, fluoruridine deoxyribose, FUdR
Drug: Dexamethasone
Other Name: Aeroseb-Dex, Decaderm, Decadron, Decaspray, DM, DXM
Drug: Gemcitabine
Other Name: dFdC, dFdCyd, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar, LY-188011
Drug: Oxaliplatin
Other Name: 1-OHP, Dacotin, Dacplat, diaminocyclohexane oxalatoplatinum, Eloxatin, L-OHP

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01525069


Contacts
Contact: William Chapman, M.D. 314-362-7792 chapmanw@wustl.edu
Contact: Tracey Guthrie 314-747-4404 guthriet@wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: William Chapman, M.D.    314-362-7792    chapmanw@wustl.edu   
Contact: Tracey Guthrie    314-747-4404    guthriet@wustl.edu   
Sub-Investigator: William Chapman, M.D.         
Sub-Investigator: M.B. Majella Doyle, M.D.         
Sub-Investigator: William Hawkins, M.D.         
Sub-Investigator: Jeffrey Lowell, M.D.         
Sub-Investigator: Joel Picus, M.D.         
Sub-Investigator: Steven Strasberg, M.D.         
Sub-Investigator: Rama Suresh, M.D.         
Sub-Investigator: Andrea Wang-Gillam, M.D., Ph.D.         
Sub-Investigator: Kathryn J. Fowler, M.D.         
Sub-Investigator: Benjamin Tan, M.D.         
Sub-Investigator: John Kotyk, M.D.         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: William Chapman, M.D. Washington University School of Medicine
  More Information

Additional Information:
Publications:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01525069     History of Changes
Other Study ID Numbers: 201111068
First Submitted: January 25, 2012
First Posted: February 2, 2012
Last Update Posted: July 2, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
Cholangiocarcinoma
Liver Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Dexamethasone acetate
Dexamethasone
Gemcitabine
Oxaliplatin
Floxuridine
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors