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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT01938729

Collaborator

Ohio State University (Other), University of Texas Southwestern Medical Center (Other), Washington University School of Medicine (Other)

Enrollment

Locations

Arm

84.2

Actual Duration (Months)

1.6

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Intrahepatic Cholangiocarcinoma Peripheral Cholangiocarcinoma Cholangiolar Carcinoma Cholangiocellular Carcinoma) (ICC)	Procedure: Liver resection and placement of hepatic artery infusion pump Drug: FLOXURIDINE Drug: DEXAMETHASONE Drug: GEMCITABINE	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

8 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 5, 2013

Actual Primary Completion Date :

Sep 10, 2020

Actual Study Completion Date :

Sep 10, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HAI with FLOXURIDINE & DEXAMETHASONE & GEMCITABINE 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	Procedure: Liver resection and placement of hepatic artery infusion pump Drug: FLOXURIDINE Drug: DEXAMETHASONE Drug: GEMCITABINE

Arm

Intervention/Treatment

Experimental: HAI with FLOXURIDINE & DEXAMETHASONE & GEMCITABINE

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

Procedure: Liver resection and placement of hepatic artery infusion pump

Drug: FLOXURIDINE

Drug: DEXAMETHASONE

Drug: GEMCITABINE

Outcome Measures

Primary Outcome Measures

Safety and Toxicity [1 year]
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 [1 year]
we will evaluate the recurrence-free survival of patients in this trial using Kaplan-Meier methods.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Cancer Center at Basking Ridge	Basking Ridge	New Jersey	United States
2	Memorial Sloan Kettering Cancer Center at Commack	Commack	New York	United States	11725
3	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
4	Memorial Sloan Kettering Cancer Center at Mercy Medical Center	Rockville Centre	New York	United States	11570
5	Memorial Sloan Kettering Cancer Center Sleepy Hollow	Sleepy Hollow	New York	United States	10591