Back to resultsHepatic Arterial Infusion in Treating Patients With Locally Advanced, Non-Metastatic Cholangiocarcinoma
Primary Purpose
Cholangiocarcinoma, Liver Neoplasms
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Floxuridine
Dexamethasone
Gemcitabine
Oxaliplatin
Sponsored by
About this trial
This is an interventional treatment trial for Cholangiocarcinoma
Eligibility 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
Sites / Locations
- Washington University School of Medicine
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Arm A (HAI FUDR alone)
Arm B (HAI FUDR + gemcitabine)
Arm C (HAI FUDR + gemcitabine + oxaliplatin)
Arm Description
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.
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.
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.
Outcomes
Primary Outcome Measures
Dose-limiting toxicities (DLTs)
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)
Describe median time to progression with a 95% confidence interval for each cohort.
Response rates
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
Number and grade of adverse events
Determine safety, tolerability and toxicities based on the number and grade of adverse events associated with this regimen.
Imaging biomarkers of tumor response
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 to progression (TTP)
Describe median time to progression with a 95% confidence interval for each cohort.
Full Information
NCT ID
NCT01525069
First Posted
January 25, 2012
Last Updated
August 8, 2022
Sponsor
Washington University School of Medicine
1. Study Identification
Unique Protocol Identification Number
NCT01525069
Brief Title
Hepatic Arterial Infusion in Treating Patients With Locally Advanced, Non-Metastatic Cholangiocarcinoma
Official Title
Pilot Study of Hepatic Arterial Infusion Therapy in Patients With Unresectable or Borderline Resectable Intrahepatic Cholangiocarcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Terminated
Why Stopped
Equipment that was used in the study was discontinued
Study Start Date
April 3, 2012 (Actual)
Primary Completion Date
August 8, 2018 (Actual)
Study Completion Date
August 2, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cholangiocarcinoma, Liver Neoplasms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A (HAI FUDR alone)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm B (HAI FUDR + gemcitabine)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm C (HAI FUDR + gemcitabine + oxaliplatin)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Floxuridine
Other Intervention Name(s)
5-FUDR, FdUrD, floxuridin, fluorodeoxyuridine, fluoruridine deoxyribose, FUdR
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
Aeroseb-Dex, Decaderm, Decadron, Decaspray, DM, DXM
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
dFdC, dFdCyd, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar, LY-188011
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
1-OHP, Dacotin, Dacplat, diaminocyclohexane oxalatoplatinum, Eloxatin, L-OHP
Primary Outcome Measure Information:
Title
Dose-limiting toxicities (DLTs)
Description
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
Time Frame
Completion of 2 cycles of treatment by all patients (approximately 4 years)
Secondary Outcome Measure Information:
Title
Time to progression (TTP)
Description
Describe median time to progression with a 95% confidence interval for each cohort.
Time Frame
12 months
Title
Response rates
Description
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
Time Frame
8 weeks
Title
Overall survival
Time Frame
12 months
Title
Number and grade of adverse events
Description
Determine safety, tolerability and toxicities based on the number and grade of adverse events associated with this regimen.
Time Frame
Beginning with pump placement and continuing for 30 days following the last day of study treatment (median length of treatment 3 months)
Title
Imaging biomarkers of tumor response
Description
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
Time Frame
Pre-treatment and then every 8 weeks during treatment (median length of treatment 3 months)
Title
Overall survival
Time Frame
Up to 5 years
Title
Time to progression (TTP)
Description
Describe median time to progression with a 95% confidence interval for each cohort.
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William Chapman, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
Citation
Valle JW WH, Palmer DD, Cunningham D, Anthoney DA, Maraveyas A, Hughes SK, Roughton JA, Bridgewater JA: Gemcitabine with or without cisplatin in patients (pts) with advanced or metastatic biliary tract cancer (ABC): Results of a multicenter, randomized phase III trial (the UK ABC-02 trial). J Clin Oncol 27:15s, 2009 (suppl, abstr 4503), 2009
Results Reference
background
PubMed Identifier
18534963
Citation
Tan BR, Brenner WS, Picus J, Marsh S, Gao F, Fournier C, Fracasso PM, James J, Yen-Revollo JL, McLeod HL. Phase I study of biweekly oxaliplatin, gemcitabine and capecitabine in patients with advanced upper gastrointestinal malignancies. Ann Oncol. 2008 Oct;19(10):1742-8. doi: 10.1093/annonc/mdn375. Epub 2008 Jun 4.
Results Reference
background
PubMed Identifier
19470932
Citation
Kemeny NE, Melendez FD, Capanu M, Paty PB, Fong Y, Schwartz LH, Jarnagin WR, Patel D, D'Angelica M. Conversion to resectability using hepatic artery infusion plus systemic chemotherapy for the treatment of unresectable liver metastases from colorectal carcinoma. J Clin Oncol. 2009 Jul 20;27(21):3465-71. doi: 10.1200/JCO.2008.20.1301. Epub 2009 May 26.
Results Reference
background
PubMed Identifier
15716576
Citation
Kemeny NE, Gonen M. Hepatic arterial infusion after liver resection. N Engl J Med. 2005 Feb 17;352(7):734-5. doi: 10.1056/NEJM200502173520723. No abstract available.
Results Reference
background
PubMed Identifier
19491285
Citation
Jarnagin WR, Schwartz LH, Gultekin DH, Gonen M, Haviland D, Shia J, D'Angelica M, Fong Y, DeMatteo R, Tse A, Blumgart LH, Kemeny N. Regional chemotherapy for unresectable primary liver cancer: results of a phase II clinical trial and assessment of DCE-MRI as a biomarker of survival. Ann Oncol. 2009 Sep;20(9):1589-1595. doi: 10.1093/annonc/mdp029. Epub 2009 Jun 2.
Results Reference
background
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
Learn more about this trial
Hepatic Arterial Infusion in Treating Patients With Locally Advanced, Non-Metastatic Cholangiocarcinoma
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