Codman Catheter/Synchromed Pump Hepatic Artery Chemotherapy for Unresectable Colorectal Metastases/Intrahepatic Cholangiocarcinoma

Feasibility Pilot of Hepatic Arterial Infusion Chemotherapy in a Rural Catchment Area, Using the Codman Vascular Catheter With the Synchromed II Pump, for Patients With Unresectable Colorectal Cancer Liver Metastases or Unresectable Intrahepatic Cholangiocarcinoma

Due to discontinuation of the Codman C3000 pump, an alternate device is necessary to continue serving patients in need of hepatic arterial infusion chemotherapy. This study aims to test the safety of hepatic artery infusion pump placement, a standard surgical procedure, and intraarterial chemotherapy initiation with the standard medication floxuridine (FUDR), using the Medtronic Synchromed II pump combined with the Codman arterial catheter in patients with unresectable (not removable by surgery) liver metastases from colorectal cancer and unresectable intrahepatic cholangiocarcinoma. This study will determine if complication and pump loss rates will be similar to previously published rates for the Codman system.

Study Overview

• Status: Terminated
• Conditions: Colorectal Neoplasms; Bile Duct Neoplasms
• Intervention / Treatment: Device: Hepatic artery infusion pump placement using the Synchromed II pump and the Codman tapered arterial catheter.; Drug: Hepatic artery infusion pump floxuridine and dexamethasone; Drug: Systemic chemotherapy for colorectal liver metastases; Drug: Systemic chemotherapy for intrahepatic cholangiocarcinoma

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients ≥ 18 years of age
• Histologically confirmed unresectable colorectal adenocarcinoma metastatic to the liver with no definitive clinical or radiographic evidence of extrahepatic disease. Clinical or radiographic evidence of metastatic disease to peri-hepatic lymph nodes will be allowed, provided it is amenable to resection.

(OR)

• Histologically confirmed unresectable non-metastatic intrahepatic cholangiocarcinoma, with presence of less than 70% liver involvement. Clinical or radiographic evidence of metastatic disease to peri-hepatic lymph nodes will be allowed, provided it is amenable to resection.
• ECOG Performance Status of 0 - 1
• Lab Values ≤ 14 days prior to study enrollment:

absolute neutrophil count ≥1,500/mcL AST/ALT < 2.5 x institutional upper limit of normal (ULN) Platelets ≥ 100,000/mcL Creatinine < 1.5 mg/dL HGB > 9 g/dL Total Bilirubin ≤ 1.5 mg/dL

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Prior chemotherapy is acceptable if last dose given ≥ 3 weeks prior to study enrollment.
• Any investigational agent is acceptable if last dose administered ≥ 3 months before study enrollment.

Exclusion Criteria:

• Presence of distant metastatic disease confirmed by radiographic evaluation. Clinical or radiographic evidence of metastatic disease to regional peri-hepatic lymph nodes will be allowed, provided it is amenable to resection.
• Prior radiation to the liver, including external beam, SBRT, Y90. Prior radiation therapy to the pelvis is acceptable.
• Active infection, hepatic encephalopathy
• Clinical evidence of portal hypertension (ascites, gastroesophageal varices or portal vein thrombosis; surgically-related ascites does not exclude the patient)
• Female patients who are pregnant or lactating - or planning to become pregnant within 6 months after the end of the treatment (female patients of child-bearing potential must have negative pregnancy test ≤72 hours before surgery)
• If in the opinion of the treating investigator a patient has any serious medical problems which may preclude receiving this type of treatment
• Patients with history or known presence of primary CNS tumors, seizures not well-controlled with standard medical therapy, or history of stroke
• Serious or non-healing active wound, ulcer, or bone fracture
• Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the HAIP chemotherapy (i.e., investigational regimen)
• Patients with psychiatric illness or social situations that would limit compliance with study requirements. Examples include: active substance abuse, active severe EtOH abuse, etc.
• Inability to reliably commit to traveling to Lexington, KY every 2 weeks for duration of the study treatment (6 months). Patient must have readily identifiable, reliable primary and back-up modes of transportation regardless of weather.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Colorectal liver metastases; Patients with unresectable colorectal liver metastases will undergo hepatic artery infusion pump placement using the Synchromed II pump and the Codman tapered arterial catheter. Patients will then receive hepatic artery infusion floxuridine as well as disease-appropriate systemic chemotherapy (FOLFOX, FOLRIRI, or oxaliplatin/irinotecan, or panitumumab if KRAS/NRAS wild type)	Device: Hepatic artery infusion pump placement using the Synchromed II pump and the Codman tapered arterial catheter.; Patients will undergo surgical hepatic artery infusion pump placement using the Synchromed II pump and the Codman tapered arterial catheter.; Drug: Hepatic artery infusion pump floxuridine and dexamethasone; Patients will receive infusion of floxuridine (FUDR) and dexamethasone via hepatic artery infusion through the implanted pump; Drug: Systemic chemotherapy for colorectal liver metastases; Patients will receive disease-appropriate systemic chemotherapy for colorectal liver metastases (FOLFOX, FOLFIRI, or irinotecan/oxaliplatin, or panitumumab if KRAS/NRAS wild type)
Experimental: Intrahepatic cholangiocarcinoma; Patients with unresectable intrahepatic cholangiocarcinoma will undergo hepatic artery infusion pump placement using the Synchromed II pump and the Codman tapered arterial catheter. Patients will then receive hepatic artery infusion floxuridine as well as disease-appropriate systemic chemotherapy (gemcitabine/oxaliplatin or gemcitabine alone)	Device: Hepatic artery infusion pump placement using the Synchromed II pump and the Codman tapered arterial catheter.; Patients will undergo surgical hepatic artery infusion pump placement using the Synchromed II pump and the Codman tapered arterial catheter.; Drug: Hepatic artery infusion pump floxuridine and dexamethasone; Patients will receive infusion of floxuridine (FUDR) and dexamethasone via hepatic artery infusion through the implanted pump; Drug: Systemic chemotherapy for intrahepatic cholangiocarcinoma; Patients will receive disease-appropriate systemic chemotherapy for intrahepatic cholangiocarcinoma (gemcitabine/oxaliplatin or gemcitabine alone)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Completion of 1st Cycle of Hepatic Artery Chemotherapy	The percent of patients who complete the 1st cycle of hepatic artery chemotherapy will be tabulated. This is a conglomerate safety endpoint which is a surrogate for any complication that prevents delivery of hepatic artery chemotherapy via the device combination.	approximately 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30-day Postoperative Serious Adverse Events Related to Pump Implantation	Tabulation of CTCAE serious adverse events attributed to pump implantation	30 days
30-day Catheter Malfunction Due to Tubing Disconnect	Quantify the percent of patients with inability to meet primary outcome due to catheter disconnects.	30 days
30-day Catheter Malfunction Due to Inability to Access Pump	Quantify the percent of patients with inability to meet primary outcome due to inability to access pump.	30 days
Percent of Patients That Require Secondary Intervention in Order to Obtain Primary Pump Function.	Percentage of patients who need secondary intervention (IR embolization, revision of pump or tubing) to achieve primary pump function.	Approximately 4 weeks
Percent of Screened Patients That Are Declined Due to High Risk of Failure as Determined by the Psychosocial Assessment Tool.	Patients are screen using a psychosocial assessment tool for high risk of hepatic artery pump loss/failure, percent declined will be tabulated.	Immediate, determined at screening visit
Percent Pump Loss Due to Inability to Attend Scheduled Followup Appointments.	Percent of patients that experience pump loss/failure due to inability to attend scheduled followup appointments will be tabulated.	Approximately 6 months
Number of Interventions (Phone Calls) to Assure Patients Attend Followup Appointments.	The number of staff contacts (phone calls) to assure patients keep their followup visits will be tabulated.	6 months
Overall Response Rate at 6 Months	RECIST v1.1 will be used to assess overall response rate at 6 months.	6 months
Percent of Patients Who Are Downstaged and Undergo Surgery	The percent of patients who are downstaged and undergo surgery will be tabulated.	6 months
Percent of Patients Who Remain on Hepatic Artery Infusion Pump Chemotherapy at 3 Months.	The percentage of patients who remain on pump chemotherapy at 3 months will be tabulated.	3 months
Percent of Patients Who Remain on Hepatic Artery Infusion Pump Chemotherapy at 6 Months.	The percentage of patients who remain on pump chemotherapy at 6months will be tabulated.	6 months

Collaborators and Investigators

• Sponsor: Michael J Cavnar, MD
• Investigators: Principal Investigator: Michael J Cavnar, MD, University of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2020
• Primary Completion (Actual): January 4, 2022
• Study Completion (Actual): June 14, 2022

Study Registration Dates

• First Submitted: February 16, 2020
• First Submitted That Met QC Criteria: February 16, 2020
• First Posted (Actual): February 19, 2020

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: July 12, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: intrahepatic cholangiocarcinoma; FUDR; colorectal liver metastases; hepatic artery infusion pump; floxuridine
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Biliary Tract Diseases; Bile Duct Diseases; Biliary Tract Neoplasms; Neoplasms; Colorectal Neoplasms; Neoplasm Metastasis; Cholangiocarcinoma; Bile Duct Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone; Floxuridine
• Other Study ID Numbers: MCC-19-GI-109-PMC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes