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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Washington University School of Medicine
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01525069
First received: January 25, 2012
Last updated: May 27, 2014
Last verified: May 2014
  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 0

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: 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:
  • Toxicity of HAI alone or in combination with systemic oxaliplatin and/or gemcitabine [ Time Frame: From first receiving study treatment until a 30-day follow up after the conclusion of treatment or death ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Time to progression [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Describe median time to progression with a 95% confidence interval for each cohort.

  • Response rates [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Describe the overall response rate and the response rate within each cohort with 95% confidence intervals.

  • Overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Describe median overall survival with a 95% confidence interval and estimate the overall survival rate at 12 and 24 months with 95% confidence intervals.

  • Number and grade of adverse events post HAI treatment [ Time Frame: From first receiving study treatment until a 30-day follow up after the conclusion of treatment or death ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 18
Study Start Date: April 2012
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort A (HAI)

14-42 days after surgery for insertion of the HAI pump, 0.16 mg/kg/day floxuridine (FUDR) and 20 mg dexamethasone plus 30,000 units of 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 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: Cohort B (HAI + gemcitabine)

Gemcitabine 1000 mg/m2 IV will be given on Days 1, 8, and 15 of each 28 day cycle.

14-42 days after surgery for insertion of the HAI pump, 0.12 mg/kg/day floxuridine (FUDR) and 20 mg dexamethasone plus 30,000 units of 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 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: Cohort C (HAI + gemcitabine + oxaliplatin)

Gemcitabine 800 mg/m2 IV will be given on Days 1 and 15 of each 28 day cycle.

Oxaliplatin 85 mg/m2 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, 0.12 mg/kg/day floxuridine (FUDR) and 20 mg dexamethasone plus 30,000 units of 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 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient must have histologically or cytologically confirmed intrahepatic or hilar cholangiocarcinoma with minimal extrahepatic disease
  • 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 within normal institutional limits
  • 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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01525069

Contacts
Contact: William Chapman, M.D. 314-362-7792 chapmanw@wustl.edu
Contact: Casey Rowe, MS, BS 314-362-8547 rowec@wudosis.wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: William Chapman, M.D.    314-362-7992    chapmanw@wustl.edu   
Contact: Casey Rowe, MS, BS    314-362-8547    rowec@wudosis.wustl.edu   
Sub-Investigator: Benjamin Tan, M.D.         
Sub-Investigator: Maria Doyle, M.D.         
Sub-Investigator: William Hawkins, M.D.         
Sub-Investigator: David Linehan, M.D.         
Sub-Investigator: A. Craig Lockhart, M.D.         
Sub-Investigator: Jeffrey Lowell, M.D.         
Sub-Investigator: Joel Picus, M.D.         
Sub-Investigator: Steven Sorscher, 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.         
Principal Investigator: William Chapman, M.D.         
Sponsors and Collaborators
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
Study First Received: January 25, 2012
Last Updated: May 27, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Cholangiocarcinoma
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Gemcitabine
Oxaliplatin
Floxuridine
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on July 29, 2014