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Hepatic Arterial Infusion (HAI) With Floxuridine (FUDR) and Dexamethasone (Dex) Combined With Systemic Gemcitabine and Oxaliplatin in Patients With Unresectable Intrahepatic Cholangiocarcinoma (ICC)

Primary Purpose

Intrahepatic Cholangiocarcinoma, Peripheral Cholangiocarcinoma, Cholangiolar Carcinoma

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Floxuridine (FUDR)
dexamethasone
Gemcitabine
Oxaliplatin
MRI
Research blood draws
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Intrahepatic Cholangiocarcinoma focused on measuring Hepatic Arterial Infusion (HAI), Floxuridine (FUDR), Dexamethasone (DEX), Gemcitabine, Oxaliplatin, 13-066

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age ≥ 21 years
  • Histologically confirmed intrahepatic cholangiocarcinoma (also variously reported as peripheral cholangiocarcinoma, cholangiolar carcinoma or cholangiocellular carcinoma) (ICC). Confirmation of the diagnosis at MSKCC or at the enrolling institution must be obtained prior to initiation of protocol therapy.
  • Clinical or radiographic evidence of metastatic disease to regional lymph nodes will be allowed, provided it is amenable to resection.
  • Radiographically measurable disease. Measurable disease is defined as disease that can be assessed with 2-dimensional measurements on a cross-sectional imaging. Minimum lesion size is 2cm in greatest diameter as per RECIST criteria.
  • Disease must be considered unresectable at the time of preoperative evaluation.
  • Presence of less than 70% liver involvement by cancer.
  • Patients may have failed ablative therapy
  • Patient previously treated with systemic chemotherapy will be eligible
  • KPS ≥ 60% and be considered candidates for general anesthesia, abdominal exploration and hepatic artery pump placement
  • Patients with chronic hepatitis and/or cirrhosis are eligible, but must be Child-Pugh class A
  • Patients must be able to read, understand and sign informed consent
  • WBC ≥ 2,000 cells/mm3
  • Platelet count ≥ 75,000/mm3
  • Creatinine ≤ 1.8 mg/dl
  • Total bilirubin < 1.5 mg/dl

Exclusion Criteria:

  • Presence of distant metastatic disease. Patients will undergo radiographic evaluation to exclude the possibility of distant metastatic disease. For patients who have undergone pre- or postoperative biopsies that definitively diagnose ICC, the diagnostic studies may be modified at the discretion of the MSKCC Principal Investigator. Clinical or radiographic evidence of metastatic disease to regional lymph nodes will be allowed, provided it is amenable to resection.
  • Prior treatment with FUDR
  • Prior external beam radiation therapy to the liver
  • Diagnosis of sclerosing cholangitis
  • Clinical evidence or portal hypertension (ascites, gastroesophageal varices, or portal vein thrombosis) surgically related ascites does not exclude the patient)
  • Active infection
  • Pregnant or lactating women
  • History of other malignancy within the past 3 years (except non-melanoma skin cancer)
  • Life expectancy less than 12 weeks
  • Inability to comply with study and/or followup procedures
  • History of peripheral neuropathy (Note: this does not apply to Cohort 3)

Sites / Locations

  • Memorial Sloan Kettering Cancer Center
  • Memorial Sloan Kettering Monmouth
  • Memorial Sloan Kettering Commack
  • Memorial Sloan Kettering Westchester
  • Memorial Sloan Kettering Cancer Center
  • Memorial Sloan Kettering Nassau

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

No prior chemo or responded/stable with prior chemo

patients who have failed systemic therapy

pts who have had prior oxaliplatin & have existing neuropathy

Arm Description

All patients receive HAI FUDR ([0.12 mg/kg/day kg 30] / pump flow rate)& dexamethasone ({1 mg/m2/day30} pump flow rate) on Day 1 of each cycle. Chemotherapy with HAI FUDR/Dex will commence no sooner than 14 days postsurgical placement of HAI pump. All patients receive Gemcitabine (800 mg/m2 IV over 30 minutes) & Oxaliplatin (85 mg/m2 IV over 120 minutes) on Days 1 & 15 of each cycle, however initiation with systemic chemotherapy will not take place until 4 weeks post-surgery for pump placement, so the first doses of systemic chemotherapy will be given on Cycle 1, Day 15, & then every 2 weeks thereafter. Clinical MRI examinations of the abdomen & pelvis are obtained at baseline following surgery, prior to treatment initiation & 4 weeks after initiation of HAI FUDR. Subsequently, the patient will undergo MRI approximately at months 3, 6 & 9 thereafter A non-contrast CT of chest, abdomen & pelvis will also be obtained as part of routine clinical care.

All patients receive HAI FUDR ([0.12 mg/kg/day kg 30] / pump flow rate)& dexamethasone ({1 mg/m2/day 30}/ pump flow rate) on day 1 of each cycle. Chemotherapy with HAI FUDR/Dex will commence no sooner than 14 days postsurgical placement of HAI pump. All patients receive Gemcitabine (800 mg/m2 IV over 30 minutes) & Oxaliplatin (85 mg/m2 IV over 120 minutes) on Days 1 & 15 of each cycle, however initiation with systemic chemotherapy will not take place until 4 weeks post-surgery for pump placement, so the first doses of systemic chemotherapy will be given on Cycle 1, Day 15, & then every 2 weeks thereafter. Clinical MRI examinations of the abdomen & pelvis are obtained at baseline following surgery, prior to treatment initiation & 4 weeks after initiation of HAI FUDR. Subsequently, the patient will undergo MRI approximately at months 3, 6 & 9 thereafter A non-contrast CT of chest, abdomen & pelvis will also be obtained as part of routine clinical care.

All patients receive will receive gemcitabine alone with HAI FUDR/Dex Gemcitabine (800 mg/m2 IV over 30 minutes) alone on Days 1 and 15 of each cycle, however initiation with systemic chemotherapy will not take place until 4 weeks post-surgery for pump placement, so the first doses of systemic chemotherapy will be given on Cycle 1, Day 15, and then every 2 weeks thereafter.

Outcomes

Primary Outcome Measures

progression free survival for Cohort 1
Treatment evaluation will be done using RECIST (version 1.1)
progression free survival for Cohort 2
Treatment evaluation will be done using RECIST (version 1.1)
response for Cohort 3
Treatment evaluation will be done using RECIST (version 1.1)

Secondary Outcome Measures

Correlative objective of of dynamic contrast enhanced (DCE)-MRI imaging of intrahepatic cholangiocarcinoma before treatment and early during the course of treatment.
This study will investigate DCE-MRI as potential imaging biomarkers and will measure tumor perfusion parameters and diffusion coefficients before initiating treatment and on follow-up MRI scans during treatment.
Correlative objective of of dynamic contrast enhanced DWI of intrahepatic cholangiocarcinoma before treatment and early during the course of treatment.
This study will investigate diffusion weighted imaging (DWI) as potential imaging biomarkers and will measure tumor perfusion parameters and diffusion coefficients before initiating treatment and on follow-up MRI scans during treatment.

Full Information

First Posted
May 20, 2013
Last Updated
June 28, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT01862315
Brief Title
Hepatic Arterial Infusion (HAI) With Floxuridine (FUDR) and Dexamethasone (Dex) Combined With Systemic Gemcitabine and Oxaliplatin in Patients With Unresectable Intrahepatic Cholangiocarcinoma (ICC)
Official Title
A Phase II Study of Hepatic Arterial Infusion (HAI) With Floxuridine (FUDR) and Dexamethasone (Dex) Combined With Systemic Gemcitabine and Oxaliplatin in Patients With Unresectable Intrahepatic Cholangiocarcinoma (ICC)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 2013 (undefined)
Primary Completion Date
May 2025 (Anticipated)
Study Completion Date
May 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center

4. Oversight

5. Study Description

Brief Summary
The purpose of this study is to use both, liver pump treatment and systemic chemotherapy, to assess the effects this type of treatment has on the patient and the tumor. Liver pump treatment uses a metal pump that is surgically placed in the abdomen and gives chemotherapy directly to the liver. Systemic chemotherapy gives chemotherapy through a vein [intravenously (IV)] and treats the whole body. This type of treatment has been done before and had shown that people with both pump and systemic chemotherapy had improved results. The investigators hope that this combination of treatments improves the response to chemotherapy and reduces the spread of the disease. Another purpose of this study is to learn the clinical importance of a specific type of MRI scan. The investigators would like to see if this type of MRI will help predict the response to the treatment and see if they could help the physician with their treatment plan. These scans will be done at specific time points. The last purpose of this study is to learn more about how the tumor interacts with the chemotherapy. This will be done through a biopsy taken during surgery and blood draws at specific time points. Permission from patients entering the study will be obtained to take normal and tumor liver biopsies at the time of surgery. These samples are voluntary and optional.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intrahepatic Cholangiocarcinoma, Peripheral Cholangiocarcinoma, Cholangiolar Carcinoma, Cholangiocellular Carcinoma
Keywords
Hepatic Arterial Infusion (HAI), Floxuridine (FUDR), Dexamethasone (DEX), Gemcitabine, Oxaliplatin, 13-066

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
55 (Actual)

8. Arms, Groups, and Interventions

Arm Title
No prior chemo or responded/stable with prior chemo
Arm Type
Experimental
Arm Description
All patients receive HAI FUDR ([0.12 mg/kg/day kg 30] / pump flow rate)& dexamethasone ({1 mg/m2/day30} pump flow rate) on Day 1 of each cycle. Chemotherapy with HAI FUDR/Dex will commence no sooner than 14 days postsurgical placement of HAI pump. All patients receive Gemcitabine (800 mg/m2 IV over 30 minutes) & Oxaliplatin (85 mg/m2 IV over 120 minutes) on Days 1 & 15 of each cycle, however initiation with systemic chemotherapy will not take place until 4 weeks post-surgery for pump placement, so the first doses of systemic chemotherapy will be given on Cycle 1, Day 15, & then every 2 weeks thereafter. Clinical MRI examinations of the abdomen & pelvis are obtained at baseline following surgery, prior to treatment initiation & 4 weeks after initiation of HAI FUDR. Subsequently, the patient will undergo MRI approximately at months 3, 6 & 9 thereafter A non-contrast CT of chest, abdomen & pelvis will also be obtained as part of routine clinical care.
Arm Title
patients who have failed systemic therapy
Arm Type
Experimental
Arm Description
All patients receive HAI FUDR ([0.12 mg/kg/day kg 30] / pump flow rate)& dexamethasone ({1 mg/m2/day 30}/ pump flow rate) on day 1 of each cycle. Chemotherapy with HAI FUDR/Dex will commence no sooner than 14 days postsurgical placement of HAI pump. All patients receive Gemcitabine (800 mg/m2 IV over 30 minutes) & Oxaliplatin (85 mg/m2 IV over 120 minutes) on Days 1 & 15 of each cycle, however initiation with systemic chemotherapy will not take place until 4 weeks post-surgery for pump placement, so the first doses of systemic chemotherapy will be given on Cycle 1, Day 15, & then every 2 weeks thereafter. Clinical MRI examinations of the abdomen & pelvis are obtained at baseline following surgery, prior to treatment initiation & 4 weeks after initiation of HAI FUDR. Subsequently, the patient will undergo MRI approximately at months 3, 6 & 9 thereafter A non-contrast CT of chest, abdomen & pelvis will also be obtained as part of routine clinical care.
Arm Title
pts who have had prior oxaliplatin & have existing neuropathy
Arm Type
Experimental
Arm Description
All patients receive will receive gemcitabine alone with HAI FUDR/Dex Gemcitabine (800 mg/m2 IV over 30 minutes) alone on Days 1 and 15 of each cycle, however initiation with systemic chemotherapy will not take place until 4 weeks post-surgery for pump placement, so the first doses of systemic chemotherapy will be given on Cycle 1, Day 15, and then every 2 weeks thereafter.
Intervention Type
Drug
Intervention Name(s)
Floxuridine (FUDR)
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Type
Other
Intervention Name(s)
MRI
Intervention Type
Other
Intervention Name(s)
Research blood draws
Intervention Description
These are optional
Primary Outcome Measure Information:
Title
progression free survival for Cohort 1
Description
Treatment evaluation will be done using RECIST (version 1.1)
Time Frame
6 months
Title
progression free survival for Cohort 2
Description
Treatment evaluation will be done using RECIST (version 1.1)
Time Frame
3 months
Title
response for Cohort 3
Description
Treatment evaluation will be done using RECIST (version 1.1)
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Correlative objective of of dynamic contrast enhanced (DCE)-MRI imaging of intrahepatic cholangiocarcinoma before treatment and early during the course of treatment.
Description
This study will investigate DCE-MRI as potential imaging biomarkers and will measure tumor perfusion parameters and diffusion coefficients before initiating treatment and on follow-up MRI scans during treatment.
Time Frame
1 year
Title
Correlative objective of of dynamic contrast enhanced DWI of intrahepatic cholangiocarcinoma before treatment and early during the course of treatment.
Description
This study will investigate diffusion weighted imaging (DWI) as potential imaging biomarkers and will measure tumor perfusion parameters and diffusion coefficients before initiating treatment and on follow-up MRI scans during treatment.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 21 years Histologically confirmed intrahepatic cholangiocarcinoma (also variously reported as peripheral cholangiocarcinoma, cholangiolar carcinoma or cholangiocellular carcinoma) (ICC). Confirmation of the diagnosis at MSKCC or at the enrolling institution must be obtained prior to initiation of protocol therapy. Clinical or radiographic evidence of metastatic disease to regional lymph nodes will be allowed, provided it is amenable to resection. Radiographically measurable disease. Measurable disease is defined as disease that can be assessed with 2-dimensional measurements on a cross-sectional imaging. Minimum lesion size is 2cm in greatest diameter as per RECIST criteria. Disease must be considered unresectable at the time of preoperative evaluation. Presence of less than 70% liver involvement by cancer. Patients may have failed ablative therapy Patient previously treated with systemic chemotherapy will be eligible KPS ≥ 60% and be considered candidates for general anesthesia, abdominal exploration and hepatic artery pump placement Patients with chronic hepatitis and/or cirrhosis are eligible, but must be Child-Pugh class A Patients must be able to read, understand and sign informed consent WBC ≥ 2,000 cells/mm3 Platelet count ≥ 75,000/mm3 Creatinine ≤ 1.8 mg/dl Total bilirubin < 1.5 mg/dl Exclusion Criteria: Presence of distant metastatic disease. Patients will undergo radiographic evaluation to exclude the possibility of distant metastatic disease. For patients who have undergone pre- or postoperative biopsies that definitively diagnose ICC, the diagnostic studies may be modified at the discretion of the MSKCC Principal Investigator. Clinical or radiographic evidence of metastatic disease to regional lymph nodes will be allowed, provided it is amenable to resection. Prior treatment with FUDR Prior external beam radiation therapy to the liver Diagnosis of sclerosing cholangitis Clinical evidence or portal hypertension (ascites, gastroesophageal varices, or portal vein thrombosis) surgically related ascites does not exclude the patient) Active infection Pregnant or lactating women History of other malignancy within the past 3 years (except non-melanoma skin cancer) Life expectancy less than 12 weeks Inability to comply with study and/or followup procedures History of peripheral neuropathy (Note: this does not apply to Cohort 3)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William Jarnagin, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
Basking Ridge
State/Province
New Jersey
Country
United States
Facility Name
Memorial Sloan Kettering Monmouth
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Facility Name
Memorial Sloan Kettering Commack
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Facility Name
Memorial Sloan Kettering Westchester
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Memorial Sloan Kettering Nassau
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mskcc.org/
Description
Memorial Sloan-Kettering Cancer Center

Learn more about this trial

Hepatic Arterial Infusion (HAI) With Floxuridine (FUDR) and Dexamethasone (Dex) Combined With Systemic Gemcitabine and Oxaliplatin in Patients With Unresectable Intrahepatic Cholangiocarcinoma (ICC)

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