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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01525069
First received: January 25, 2012
Last updated: October 17, 2014
Last verified: October 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:
  • Dose-limiting toxicities (DLTs) [ Time Frame: Completion of 2 cycles of treatment by all patients (approximately 4 years) ] [ 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 during the first 2 cycles of treatment


Secondary Outcome Measures:
  • Time to progression (TTP) [ Time Frame: 12 months ] [ 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 ]

    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 ] [ Designated as safety issue: No ]
  • 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) ] [ 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 (median length of treatment 3 months) ] [ 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

  • Overall survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Time to progression (TTP) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Describe median time to progression with a 95% confidence interval for each cohort.


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: 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

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

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
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
Study First Received: January 25, 2012
Last Updated: October 17, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Cholangiocarcinoma
Liver Neoplasms
Adenocarcinoma
Carcinoma
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Floxuridine
Gemcitabine
Oxaliplatin
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Antiviral Agents
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents

ClinicalTrials.gov processed this record on October 23, 2014