Hepatic Artery Infusion (HAI) Program at Duke University

The Duke HAI program was implemented in November 2018 and treated 30 patients in its first 17 months using the Medtronic Synchromed II device (only commercially available device suitable for HAI for cancer patients). The Duke HAI program has demonstrated safety of HAI with an overall complication rate was 19%, similar to prior published data, with all but one complication (extrahepatic perfusion) salvaged. The Investigator has also demonstrated feasibility and efficacy of a new HAI program, with 95% of patients initiating therapy with promising hepatic response and disease control rates. This protocol will enable the team to continue this program. All eligible patients will receive the synchromed II pump with a Codman catheter and chemotherapy including FUDR, dexamethasone and heparin. Systemic chemotherapy will be given per standard of care.

Study Overview

• Status: Withdrawn
• Conditions: Intrahepatic Cholangiocarcinoma; Liver Cancer; Metastatic Colon Cancer
• Intervention / Treatment: Device: Medtronic Synchromed II pump

Detailed Description

This protocol is an interventional study for HAI therapy at Duke. The protocol is essentially for clinical treatment and the Investigator is not collecting safety and effectiveness data on the device itself. There are three primary indications for the hepatic artery infusion pump. The first are patients with unresectable, metastatic, liver-only or -dominant colorectal cancer. Although conversion to resection is a primary goal in these patients, most of these patients will die of liver disease and therefore controlling liver disease is a secondary goal to improve survival. The second group of patients are those with resectable, but high risk metastatic, liver-only or -dominant colorectal cancer. These patients are at high risk for liver recurrence, and HAI has demonstrated significant improvement in outcomes. The last group are patients with unresectable primary liver cancer, primarily intrahepatic cholangiocarcinoma. These patients have central tumors that are rarely resectable.

Eligible patients will have the following procedures performed during this study.

1. On the day of surgery, the Synchromed II pump will be implanted and the Codman® catheter placed for chemotherapy infusion.

2. During the hospital stay, patients will have:

   • Daily physical examination to evaluate for the development of complications
   • Daily blood tests to evaluate blood cell counts and liver function
   • Initiation of a proton-pump inhibitor, if not already a home medication, which will continue indefinitely
   • Assessment of side effects

Follow-Up Visits

Clinic visits and study activities will take place every 2 weeks after surgery, and include:

• Routine blood tests for blood cell counts, kidney function, and liver function
• Nuclear medicine SPECT/CT scan to confirm the pump and catheter are working properly. This is a type of scan where the images or pictures from two different types of scans are combined together.
• Start hepatic artery infusion (HAI) chemotherapy (at 2 week post-op).

HAI includes:

• Floxuridine (FUDR)
• Dexamethasone
• Heparin: (If heparin allergy, fondaparinux will be added)
• Normal saline

• Evaluation and treatment, including blood work and refilling the pump, every 2 weeks, until treatment is discontinued.

  • Systemic chemotherapy (every 2 weeks after HAI started)

• Patients with metastatic colorectal cancer will receive systemic chemotherapy that will consist of either FOLFIRI, FOLFOX, or Irinotecan/oxaliplatin.
• Patients with cholangiocarcinoma will receive Gemcitabine/Oxaliplatin or Gemcitabine alone

When the chemotherapy regimen has completed, the Synchromed II pump will be reprogrammed every 4 weeks indefinitely.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients age 18-80
• Eastern Cooperative Oncology Group score 0-1
• Fit for major surgery
• Without evidence of cirrhosis or portal hypertension
• Labs within 14 days of surgery: White blood cells ≥3 k/uL, Absolute Neutrophil Count ≥ 1.5 k/uL, Platelets ≥ 100K /uL, Creatinine ≤ 1.5 mg/dL, Total bilirubin ≤1.5 mg/dL
• Disease should be liver-only or liver-dominant
• Arterial anatomy must be suitable, determined by the surgeon
• Primary tumor may be in place in the case of colorectal liver metastases. Patients may have colorectal liver metastases (unresectable, borderline resectable, resectable), or unresectable intrahepatic cholangiocarcinoma.
• Chemotherapy completed at least 3 weeks prior to surgery.

Exclusion Criteria:

• Patients younger than 18 or older than 80 years
• Eastern Cooperative Oncology Group score 2+
• Unfit for major surgery
• Inherent liver disease with evidence of cirrhosis or portal hypertension
• Widely metastatic disease is absolutely contraindicated
• Pregnant women (Women of childbearing potential who have not completed menopause, had a hysterectomy and/or both tubes and/or both ovaries removed and have a partner who is able to father children will have a blood or urine pregnancy test performed, and it must be negative in order to continue in the study.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Hepatic Artery Infusion (HAI); The Medtronic Synchromed II pump with the Codman® Catheter will be used to create the investigational device. The Medtronic Synchromed II pump is a surgically implantable device that allows for the delivery of high doses of chemotherapy directly to the liver, in order to treat cancer. The device is surgically implanted into a subcutaneous pocket in the abdominal wall, and the catheter is inserted into the arterial system of the liver, allowing for chemotherapeutic delivery.

Device: Medtronic Synchromed II pump; The pump will be placed during surgery and the pump will be filled with a combination of floxuridine (FUDR), dexamethasone, heparin, and saline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients Treated	Number of patients who completed HAI therapy	Surgery to 6 months post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious Adverse Events	SAEs experienced by patients receiving the synchromed II pump and HAI therapy	Surgery to one year post-surgery

Collaborators and Investigators

• Sponsor: Michael Lidsky, M.D.
• Investigators: Principal Investigator: Michael Lidsky, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2020
• Primary Completion (Anticipated): June 30, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: August 11, 2020
• First Submitted That Met QC Criteria: August 11, 2020
• First Posted (Actual): August 13, 2020

Study Record Updates

• Last Update Posted (Actual): July 19, 2021
• Last Update Submitted That Met QC Criteria: July 13, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma
• Other Study ID Numbers: Pro00106190

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