Hepatic Artery Infusional Floxuridine to Treat Pancreatic Cancer Liver Metastases

Study Overview
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Brief Summary
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This is a single arm, phase II study without blinding. The purpose is to determine the impact of hepatic artery infusion Floxuridine (FUDR) on liver metastases from pancreatic adenocarcinoma. Patients at Spectrum Health will receive standard of care chemotherapy. They will also receive chemotherapy via surgically placed hepatic artery infusion (HAI) pump.

Detailed Description
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This study hypothesizes that the combination of Floxuridine (FUDR), a type of chemotherapy, delivered via a hepatic artery infusion (HAI) pump, with standard of care systemic chemotherapy will lead to improved survival in the treatment of pancreatic cancer liver metastases. Patients will receive 6 cycles of FUDR and will be followed for two years.

Official Title
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A Phase II Trial of Hepatic Artery Infusional Floxuridine With Systemic Chemotherapy in the Treatment of Pancreatic Cancer Liver Metastases

Conditions
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Pancreatic Adenocarcinoma, Liver Metastases

Intervention / Treatment
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* Drug: Floxuridine (FUDR)
* Device: Hepatic Artery Infusion Pump
* Drug: Heparinized Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy-proved pancreatic adenocarcinoma with synchronous liver metastases Elevated Cancer Antigen 19-9 (CA19-9) at diagnosis (>37 U/mL) Ages 18-75 years Karnofsky performance status ≥70 Ability to undergo general anesthesia and HAI pump placement procedure CT or MRI scan imaging of the abdomen demonstrating accessibility of the gastroduodenal artery within 2 months of enrollment Received a minimum of 2 months of systemic chemotherapy with stable tumor markers and imaging. Exclusion Criteria: Primary tumor resected Model for End Stage Liver Disease (MELD) score >20, using the variables of: Bilirubin, serum Sodium, International Normalized Ratio (INR), serum Creatinine, and Dialysis twice in the past week. Greater than 60% liver parenchymal involvement by tumor Evidence of peritoneal metastases Current alcohol abuse Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single arm study without blinding
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Floxuridine (FUDR) via HAI pump<br>Once enrolled, patients will undergo surgical placement of the HAI pump. This can be accomplished using minimally invasive or open techniques with an anticipated hospital stay of approximately 3-5 days. Prior to discharge from the hospital or at the first postoperative visit the pump is filled with FUDR according to the following equation: 0.12 mg/kg/d (using ideal body weight). This fill initiates day 1 of a 4-week cycle. The chemotherapy is infused by the pump continuously over 14 days. On day 15 (+/-4 days), the remaining chemotherapy is removed from the pump which is refilled with heparinized saline (30,000 units). This remains for an additional 2 weeks until the pump is refilled with FUDR at the start of the next cycle. Treatment is continued for a maximum of 6 cycles or as limited by toxicity. This regimen has been utilized with an acceptable safety profile in the setting of colorectal liver metastases. | Drug: Floxuridine (FUDR)<br>* Together the FUDR and the HAI pump are experimental because they are being used to treat hepatic liver metastases of Pancreatic adenocarcinoma. They have not yet been FDA approved for this indication, although they are both approved for other indications. The intervention is surgical placement of an HAI pump with subsequent delivery of FUDR via the pump in 28-day cycles. FUDR will be delivered via the HAI pump for 6 months, in 28 day cycles: 2 weeks of therapy, followed by 2 weeks of heparinized saline.<br>* Other names: FUDR;Device: Hepatic Artery Infusion Pump<br>* Together the FUDR and the HAI pump are experimental because they are being used to treat hepatic liver metastases of Pancreatic adenocarcinoma. They have not yet been FDA approved for this indication, although they are both approved for other indications. The intervention is surgical placement of an HAI pump with subsequent delivery of FUDR via the pump in 28-day cycles. The primary tumor will be resected or ablated with irreversible electroporation at the time of HAI pump placement. FUDR will be delivered via the HAI pump for 6 months, in 28 day cycles: 2 weeks of therapy, followed by 2 weeks of heparinized saline.<br>* Other names: Medtronic pump;Drug: Heparinized Saline<br>* Together the FUDR and the HAI pump are experimental because they are being used to treat hepatic liver metastases of Pancreatic adenocarcinoma. They have not yet been FDA approved for this indication, although they are both approved for other indications. FUDR will be delivered via the HAI pump for 6 months, in 28 day cycles: 2 weeks of therapy, followed by 2 weeks of heparinized saline.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hepatic progression-free survival | The length of time from the start of trial therapy to the time when target liver lesions show progression or new lesions appear. (Determined by RECIST criteria: ≥20% growth in target lesions and/or appearance of new lesions). | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | The length of time from diagnosis to death, measured as the proportion of patients surviving at specific time points (6, 12 and 18 months from diagnosis). | 2 years | 
| Progression-free survival at any site | The length of time from diagnosis to disease progression at any anatomical site (as determined by RECIST criteria) or death. | 2 years | 
| Rate of tumor response in the liver | Determined by RECIST criteria on imaging studies done every 3 months | 2 years | 
| EORTC Quality of Life Questionnaire | As measured by the EORTC Quality of Life Questionnaire Core 30 instrument | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic cancer, pancreatic ductal carcinoma, liver metastases, HAI, hepatic artery infusion pump, FUDR, Floxuridine