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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

January 25, 2012
October 17, 2014
April 2012
April 2016   (final data collection date for primary outcome measure)
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
Toxicity of HAI alone or in combination with systemic oxaliplatin and/or gemcitabine [ Time Frame: 8 weeks ] [ 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.
Complete list of historical versions of study NCT01525069 on ClinicalTrials.gov Archive Site
  • 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.
  • 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: 13 months ] [ Designated as safety issue: Yes ]
    Determine safety, tolerability and toxicities based on the number and grade of adverse events associated with this regimen.
Not Provided
Not Provided
 
Hepatic Arterial Infusion in Treating Patients With Locally Advanced, Non-Metastatic Cholangiocarcinoma
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.

Not Provided
Interventional
Phase 0
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Cholangiocarcinoma
  • Liver Neoplasms
  • 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
  • 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.
    Interventions:
    • Drug: Floxuridine
    • Drug: Dexamethasone
  • 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.
    Interventions:
    • Drug: Floxuridine
    • Drug: Dexamethasone
    • Drug: Gemcitabine
  • 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.
    Interventions:
    • Drug: Floxuridine
    • Drug: Dexamethasone
    • Drug: Gemcitabine
    • Drug: Oxaliplatin

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
18
April 2016
April 2016   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01525069
201111068
No
Washington University School of Medicine
Washington University School of Medicine
Not Provided
Principal Investigator: William Chapman, M.D. Washington University School of Medicine
Washington University School of Medicine
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP