search
Back to results

Hepatic Arterial Infusion With Floxuridine and Dexamethasone in Combination With Gemcitabine as Adjuvant Treatment After Resection of Intrahepatic Cholangiocarcinoma

Primary Purpose

Intrahepatic Cholangiocarcinoma, Peripheral Cholangiocarcinoma, Cholangiolar Carcinoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Liver resection and placement of hepatic artery infusion pump
FLOXURIDINE
DEXAMETHASONE
GEMCITABINE
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, FLOXURIDINE, DEXAMETHASONE, GEMCITABINE, Pump, 13-148

Eligibility Criteria

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

Inclusion Criteria:

  • Histologically confirmed intrahepatic cholangiocarcinoma (also variously reported as peripheral cholangiocarcinoma, cholangiolar carcinoma or cholangiocellular carcinoma) (ICC). Confirmation of the diagnosis must be made at MSKCC or at the participating institution prior to initiating protocol therapy.
  • Technically resectable, single tumors of any size, tumors with satellite nodules within 2 cm of the primary tumor that are resectable. Limited and resectable multi-focal disease (less than 4 tumors technically resectable).
  • Patients with elevated liver function tests including jaundiced patients (due to tumor) can be selectively operated on without resolution of jaundice preoperatively according to the judgment of the operating surgeon
  • Patients must have a KPS > 80% and be considered candidates for general anesthesia, hepatic resection and hepatic artery pump placement.
  • Laboratory values within 14 days before registration must be:
  • Serum albumin must be >2.5 g/dl
  • Creatinine must be < 1.8 mg/dL
  • WBC must be >3500 cells/mm3
  • Platelet count must be >100,000/mm3
  • International normalized ratio (INR) must be less than 1.5 in patients not on Coumadin therapy
  • Technically resectable, single tumors of any size, tumors with satellite nodules within 2 cm of the primary tumor that are resectable. Limited and resectable multi- focal disease (less than 4 tumors technically resectable).
  • Patients with elevated liver function tests including jaundiced patients (due to tumor) can be selectively operated on without resolution of jaundice preoperatively according to the judgment of the operating surgeon
  • Age >18 years
  • Patients must be able to understand and sign informed consent
  • Prior chemotherapy is allowed

Exclusion Criteria:

  • Prior treatment with HAI chemotherapy
  • Extrahepatic metastases including nodal disease
  • Prior external beam radiation therapy to the liver
  • Diagnosis of sclerosing cholangitis
  • Diagnosis of Gilbert's disease
  • Clinical ascites
  • Hepatic encephalopathy
  • Patients who have radiographic evidence of esophageal varices or history of variceal hemorrhage
  • Patients with occlusion of the main portal vein or of the right and left portal branches
  • Patients that have concurrent malignancies (except localized basal cell or squamous cell skin cancers)
  • Female patients who are pregnant or lactating

Sites / Locations

  • Memorial Sloan Kettering Cancer Center at Basking Ridge
  • Memorial Sloan Kettering Cancer Center at Commack
  • Memorial Sloan Kettering Cancer Center
  • Memorial Sloan Kettering Cancer Center at Mercy Medical Center
  • Memorial Sloan Kettering Cancer Center Sleepy Hollow

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HAI with FLOXURIDINE & DEXAMETHASONE & GEMCITABINE

Arm Description

This is an open-label single arm study. multi-institution phase I dose escalating trial of adjuvant HAIP FUDR and Gemcitabine chemotherapy after curative resection of ICC. Hepatectomy with or without bile duct reconstruction and pump placement are performed. The patients will start therapy 4 weeks postoperatively. They will receive HAI FUDR/Dex and systemic gemcitabine in the following dose escalation levels of gemcitabine. The dose of HAI FUDR will be fixed. A classic 3+3 cohort dose escalation scheme will be used to identify the MTD of the combination. Level 1: Systemic gemcitabine 650mg/m^2 Day 1 and 15 and HAI FUDR/Dex 0.12mg/kg/day Day 1-14 Level 2.Systemic gemcitabine 800mg/m^2 Day 1 and 15 HAI FUDR/Dex 0.12 mg/kg/day Day 1-14 Level 3. Systemic gemcitabine 1000mg/m^2 Day 1 and 15 HAI FUDR/Dex 0.12 mg/kg/day Day 1-14

Outcomes

Primary Outcome Measures

Safety and Toxicity
All toxicities will be rated as per the NCI Common Toxicity Criteria (CTC AE version 4.0) except neurosensory and hepatic enzyme toxicities related to intrahepatic pump therapy.

Secondary Outcome Measures

Recurrence Free Survival
we will evaluate the recurrence-free survival of patients in this trial using Kaplan-Meier methods.

Full Information

First Posted
September 5, 2013
Last Updated
September 10, 2020
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Ohio State University, University of Texas Southwestern Medical Center, Washington University School of Medicine
search

1. Study Identification

Unique Protocol Identification Number
NCT01938729
Brief Title
Hepatic Arterial Infusion With Floxuridine and Dexamethasone in Combination With Gemcitabine as Adjuvant Treatment After Resection of Intrahepatic Cholangiocarcinoma
Official Title
Phase I Study of Hepatic Arterial Infusion With Floxuridine and Dexamethasone in Combination With Gemcitabine as Adjuvant Treatment After Resection of Intrahepatic Cholangiocarcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
September 5, 2013 (Actual)
Primary Completion Date
September 10, 2020 (Actual)
Study Completion Date
September 10, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Ohio State University, University of Texas Southwestern Medical Center, Washington University School of Medicine

4. Oversight

5. Study Description

Brief Summary
This is a Phase I study, which means we want to find out what effects, good and/or bad, this combination of drugs may have on the patient and the liver cancer at different dose levels. All patients will have an operation to remove tumors in the liver and may have a pump placed in their abdomen. On this study, both drugs given have been used in other patients for treatment of cholangiocarcinoma and other gastrointestinal cancers. Both drugs are approved by the food and drug administration (FDA) for treatment of liver cancer, but the two drugs have only been combined in a few patients. That means that in this trial we also want to find out if this combination is safe. The study will also evaluate if this treatment works in delaying or stopping the cancer from coming back after surgery.

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) (ICC)
Keywords
HEPATIC ARTERIAL INFUSION, FLOXURIDINE, DEXAMETHASONE, GEMCITABINE, Pump, 13-148

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HAI with FLOXURIDINE & DEXAMETHASONE & GEMCITABINE
Arm Type
Experimental
Arm Description
This is an open-label single arm study. multi-institution phase I dose escalating trial of adjuvant HAIP FUDR and Gemcitabine chemotherapy after curative resection of ICC. Hepatectomy with or without bile duct reconstruction and pump placement are performed. The patients will start therapy 4 weeks postoperatively. They will receive HAI FUDR/Dex and systemic gemcitabine in the following dose escalation levels of gemcitabine. The dose of HAI FUDR will be fixed. A classic 3+3 cohort dose escalation scheme will be used to identify the MTD of the combination. Level 1: Systemic gemcitabine 650mg/m^2 Day 1 and 15 and HAI FUDR/Dex 0.12mg/kg/day Day 1-14 Level 2.Systemic gemcitabine 800mg/m^2 Day 1 and 15 HAI FUDR/Dex 0.12 mg/kg/day Day 1-14 Level 3. Systemic gemcitabine 1000mg/m^2 Day 1 and 15 HAI FUDR/Dex 0.12 mg/kg/day Day 1-14
Intervention Type
Procedure
Intervention Name(s)
Liver resection and placement of hepatic artery infusion pump
Intervention Type
Drug
Intervention Name(s)
FLOXURIDINE
Intervention Type
Drug
Intervention Name(s)
DEXAMETHASONE
Intervention Type
Drug
Intervention Name(s)
GEMCITABINE
Primary Outcome Measure Information:
Title
Safety and Toxicity
Description
All toxicities will be rated as per the NCI Common Toxicity Criteria (CTC AE version 4.0) except neurosensory and hepatic enzyme toxicities related to intrahepatic pump therapy.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Recurrence Free Survival
Description
we will evaluate the recurrence-free survival of patients in this trial using Kaplan-Meier methods.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed intrahepatic cholangiocarcinoma (also variously reported as peripheral cholangiocarcinoma, cholangiolar carcinoma or cholangiocellular carcinoma) (ICC). Confirmation of the diagnosis must be made at MSKCC or at the participating institution prior to initiating protocol therapy. Technically resectable, single tumors of any size, tumors with satellite nodules within 2 cm of the primary tumor that are resectable. Limited and resectable multi-focal disease (less than 4 tumors technically resectable). Patients with elevated liver function tests including jaundiced patients (due to tumor) can be selectively operated on without resolution of jaundice preoperatively according to the judgment of the operating surgeon Patients must have a KPS > 80% and be considered candidates for general anesthesia, hepatic resection and hepatic artery pump placement. Laboratory values within 14 days before registration must be: Serum albumin must be >2.5 g/dl Creatinine must be < 1.8 mg/dL WBC must be >3500 cells/mm3 Platelet count must be >100,000/mm3 International normalized ratio (INR) must be less than 1.5 in patients not on Coumadin therapy Technically resectable, single tumors of any size, tumors with satellite nodules within 2 cm of the primary tumor that are resectable. Limited and resectable multi- focal disease (less than 4 tumors technically resectable). Patients with elevated liver function tests including jaundiced patients (due to tumor) can be selectively operated on without resolution of jaundice preoperatively according to the judgment of the operating surgeon Age >18 years Patients must be able to understand and sign informed consent Prior chemotherapy is allowed Exclusion Criteria: Prior treatment with HAI chemotherapy Extrahepatic metastases including nodal disease Prior external beam radiation therapy to the liver Diagnosis of sclerosing cholangitis Diagnosis of Gilbert's disease Clinical ascites Hepatic encephalopathy Patients who have radiographic evidence of esophageal varices or history of variceal hemorrhage Patients with occlusion of the main portal vein or of the right and left portal branches Patients that have concurrent malignancies (except localized basal cell or squamous cell skin cancers) Female patients who are pregnant or lactating
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrea Cercek, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center at Basking Ridge
City
Basking Ridge
State/Province
New Jersey
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center at Commack
City
Commack
State/Province
New York
ZIP/Postal Code
11725
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 Cancer Center at Mercy Medical Center
City
Rockville Centre
State/Province
New York
ZIP/Postal Code
11570
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center Sleepy Hollow
City
Sleepy Hollow
State/Province
New York
ZIP/Postal Code
10591
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 With Floxuridine and Dexamethasone in Combination With Gemcitabine as Adjuvant Treatment After Resection of Intrahepatic Cholangiocarcinoma

We'll reach out to this number within 24 hrs