Hepatic Artery Infusional Floxuridine to Treat Pancreatic Cancer Liver Metastases

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

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.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Adenocarcinoma; Liver Metastases
• Intervention / Treatment: Drug: Floxuridine (FUDR); Device: Hepatic Artery Infusion Pump; Drug: Heparinized Saline

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: G. Paul Wright, MD; Phone Number: 616-486-6333; Email: paul.wright@spectrumhealth.org
• Study Contact Backup: Name: Esther Peariso, MSN, RN; Phone Number: 6164860358; Email: esther.peariso@corewellhealth.org

Study Locations

• United States
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Recruiting
      • Spectrum Health
      • Contact: Murwarid M Assifi, MD; Phone Number: 616-267-8540; Email: mura.assifi@spectrumhealth.org
      • Contact: Esther L Peariso, BSN; Phone Number: 616-486-0358; Email: esther.peariso@corewellhealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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: Floxuridine (FUDR) via HAI pump; 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); 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.; Other Names: FUDR; Device: Hepatic Artery Infusion Pump; 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.; Other Names: HAI pump; Medtronic pump; Drug: Heparinized Saline; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Spectrum Health Hospitals
• Investigators: Principal Investigator: G. Paul Wright, MD, Corewell Health

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2019
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: February 25, 2019
• First Submitted That Met QC Criteria: February 25, 2019
• First Posted (Actual): February 27, 2019

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: January 5, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: pancreatic cancer, pancreatic ductal carcinoma, liver metastases, HAI, hepatic artery infusion pump, FUDR, Floxuridine
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Liver Diseases; Neoplastic Processes; Pancreatic Diseases; Neoplasm Metastasis; Pancreatic Neoplasms; Liver Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Floxuridine
• Other Study ID Numbers: 2017-349

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes