Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Cholangiocarcinoma

Liver Neoplasms

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Bile Duct Cancer

Intrahepatic Cholangiocarcinoma

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Fibrinolytic Agents

Anticoagulants

Hematinics

Dexamethasone

Heparin

Dexamethasone acetate

Liver Extracts

Calcium heparin

Floxuridine

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.

The pump will be placed during surgery and the pump will be filled with a combination of floxuridine (FUDR), dexamethasone, heparin, and saline.

Medtronic Synchromed II pump

Michael Lidsky, MD

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.

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.

Hepatic Artery Infusion (HAI) Program at Duke University

Number of patients who completed HAI therapy

SAEs experienced by patients receiving the synchromed II pump and HAI therapy

Michael Lidsky, M.D.

Assistant Professor of Surgery

Symptoms and General Pathology

Neoplasm Metastasis

Disease Progression

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplastic Processes

Micronutrients

Irinotecan

Cetuximab

Leucovorin

Fluorouracil

Oxaliplatin

Panitumumab

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Immunological

HAIP chemotherapy + Systemic chemotherapy

implanted Medtronic SynchroMed II Pump with codman 3000 Constant Flow Pump Catheter

Codman 3000 constant flow pump catheter

HAIP will be filled with mixture of Floxuridine and Dexamethasone. Pump will perfuse drugs to liver for 14 days. Floxuridine (0.12 mg/kg X pump volume X pump flow rate),Dexamethasone (1 mg/day X pump volume (30) X pump flow rate)

FUDR-Dex

2000 mg/m2, IV 46-hour infusion of 5-Fluorouracil + 400 mg/m2, IV of Leucovorin

HAIP installation

cetuximab

implanted Medtronic SynchroMed II Pump with Codman 3000 Constant Flow Pump Catheter

Medtronic SynchroMed II Pump

Kathleen M Smith, R.N.

Jonathan M Hernandez, M.D.

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

Background:

Many people with colorectal cancer get liver metastases. Standard treatment for this is a combination of chemotherapy drugs. Directing the chemotherapy to the liver may be effective. A device that does this a pump that delivers drugs over 2 weeks at constant rate into the hepatic artery. The person s body temperature causes the drug to flow from the pump. Researchers want to see if this helps people with colorectal metastases to the liver.

Objective:

To study the effectiveness of a hepatic artery infusion pump at treating colorectal metastases to the liver.

Eligibility:

Adults at least 18 years old with colorectal metastases to the liver

Design:

Participants will be screened with:

Medical history

Physical exam

Heart, blood, and urine tests

Scans

Participants will stay in the hospital a few days. A small plastic tube (catheter) will be inserted in an artery into the liver. The catheter will be attached to the pump. That will lie under the skin on the abdomen. It will be small and participants will be able to feel it.

Participants will get treatment in 28-day cycles.

Every Day 1, they will have physical exam, symptom review, and blood tests.

Every 2 weeks, they will come to the clinic to get chemotherapy by a catheter or port.

Every 12 weeks, they will have a scan.

Tissue samples may be taken during the study.

When they finish the drug, participants may have the pump removed. They will repeat the Day 1 tests. They will be called every 6 months to see how they are doing.

Background:

* Nearly 60% of patients with colorectal cancers will develop liver metastases over the course of their disease.
* Of patients with metastatic colorectal cancer, the liver will be the sole site of recurrence or the survival-limiting site of disease for 20%.
* Liver directed therapy, which has taken many forms over the last several decades, is a potential means to prolong survival for properly selected patients and delay progression at that site.
* Hepatic artery infusion of floxuridine (FUDR) via an implantable hepatic artery infusion pump (HAIP) induces objective clinical response rates of nearly 50% in heavily pre-treated patients with metastatic colorectal cancer to the liver.
* The identification of patients likely to respond to HAIP and those likely to suffer pumprelated adverse events is currently unknown, and has limited the wide-spread adoption of this otherwise well tolerated intervention.

Objective:

* To assess the safety of hepatic artery infusion therapy using the Medtronic pump with the Codman catheter.
* To determine the response rate in patients with unresectable metastatic colorectal cancer treated with HAIP chemotherapy as measured by RECIST.

Eligibility:

* Histologically or cytologically confirmed colorectal adenocarcinoma metastatic to the liver.
* Patients with liver metastases not amenable to resection to No Evidence of Disease (NED) in one stage.
* Patients must have received systemic chemotherapy.
* Age greater than or equal to 18 years.

Design:

- Single arm, Phase II study of HAIP chemotherapy.

Hepatic Artery Infusion Pump Chemotherapy With Floxuridine and Dexamethasone in Combination With Systemic Chemotherapy for Patients With Colorectal Cancer Metastatic to the Liver

A Single-Arm Phase II Study of Hepatic Artery Infusion Pump Chemotherapy With Floxuridine and Dexamethasone in Combination With Systemic Chemotherapy for Patients With Colorectal Cancer Metastatic to the Liver

.All IPD recorded in the medical record will be shared with intramural investigators upon request.

The fraction of patients who experience a PR or CR using the study treatment

Median amount of time subject survives after therapy

The fraction of patients whose tumors in liver shrunk after therapy

The fraction of patients whose tumors outside liver shrunk after therapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Hepatic Artery Infusion (HAI) Program at Duke University	NCT04511793	Metastatic Colo... Liver Cancer Intrahepatic Ch...	Medtronic Synch...	18 Years - 80 Years	Duke University
Hepatic Artery Infusion (HAI) Program at Duke University	NCT04511793	Metastatic Colo... Liver Cancer Intrahepatic Ch...	Medtronic Synch...	18 Years - 80 Years	Duke University
Hepatic Artery Infusion Pump Chemotherapy With Floxuridine and Dexamethasone in Combination With Systemic Chemotherapy for Patients With Colorectal Cancer Metastatic to the Liver	NCT03366155	Colorectal Canc... Liver Metastase... Colorectal Aden... Colorectal Canc... Colorectal Carc...	Codman 3000 con... Panitumumab FUDR-Dex Oxaliplatin 5FU Irinotecan HAIP installati... cetuximab Medtronic Synch...	18 Years -	National Institutes of Health Clinical Center (CC)
Hepatic Artery Infusion Pump Chemotherapy With Floxuridine and Dexamethasone in Combination With Systemic Chemotherapy for Patients With Colorectal Cancer Metastatic to the Liver	NCT03366155	Colorectal Canc... Liver Metastase... Colorectal Aden... Colorectal Canc... Colorectal Carc...	Codman 3000 con... Panitumumab FUDR-Dex Oxaliplatin 5FU Irinotecan HAIP installati... cetuximab Medtronic Synch...	18 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for medtronic synchromed ii pump