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

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

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.

Study Overview

• Status: Completed
• Conditions: Intrahepatic Cholangiocarcinoma; Peripheral Cholangiocarcinoma; Cholangiolar Carcinoma; Cholangiocellular Carcinoma) (ICC)
• Intervention / Treatment: Drug: DEXAMETHASONE; Procedure: Liver resection and placement of hepatic artery infusion pump; Drug: FLOXURIDINE; Drug: GEMCITABINE

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States
      • Memorial Sloan Kettering Cancer Center at Basking Ridge
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Cancer Center at Commack
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Rockville Centre, New York, United States, 11570
      • Memorial Sloan Kettering Cancer Center at Mercy Medical Center
    • Sleepy Hollow, New York, United States, 10591
      • Memorial Sloan Kettering Cancer Center Sleepy Hollow

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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

Drug: DEXAMETHASONE; Procedure: Liver resection and placement of hepatic artery infusion pump; Drug: FLOXURIDINE; Drug: GEMCITABINE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence Free Survival	we will evaluate the recurrence-free survival of patients in this trial using Kaplan-Meier methods.	1 year

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Washington University School of Medicine; Ohio State University; University of Texas Southwestern Medical Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 5, 2013
• Primary Completion (ACTUAL): September 10, 2020
• Study Completion (ACTUAL): September 10, 2020

Study Registration Dates

• First Submitted: September 5, 2013
• First Submitted That Met QC Criteria: September 5, 2013
• First Posted (ESTIMATE): September 10, 2013

Study Record Updates

• Last Update Posted (ACTUAL): September 11, 2020
• Last Update Submitted That Met QC Criteria: September 10, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: DEXAMETHASONE; GEMCITABINE; Pump; FLOXURIDINE; HEPATIC ARTERIAL INFUSION; 13-148
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Carcinoma; Cholangiocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Gemcitabine; Dexamethasone; Floxuridine
• Other Study ID Numbers: 13-148