Floxuridine for Pancreatic Cancer

Overseen By Esther Peariso, MSN, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Spectrum Health Hospitals

Disqualifiers: Primary tumor resected, MELD >20, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat pancreatic cancer that has spread to the liver. Researchers are testing Floxuridine, a chemotherapy drug, delivered directly to the liver through a special pump to determine its effectiveness in reducing liver metastases. Individuals with pancreatic cancer that has spread to the liver and who have already received some chemotherapy might be suitable candidates. Participants should be able to undergo surgery to place the pump and have specific levels of a cancer marker in their blood. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to potentially groundbreaking advancements in cancer care.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, since it mentions that patients will receive standard of care chemotherapy, it might be possible to continue some existing treatments. Please consult with the trial coordinators for specific guidance.

Is there any evidence suggesting that Floxuridine (FUDR) via hepatic artery infusion pump is likely to be safe for humans?

Research has shown that using Floxuridine (FUDR) directly in the liver safely treats liver tumors from colon cancer. Patients typically tolerated the treatment well without serious side effects. Although this trial focuses on pancreatic cancer, past studies with similar treatments suggest that FUDR can be used safely. However, as this trial is just beginning, the safety of the treatment remains under close monitoring. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pancreatic cancer?

Floxuridine (FUDR) for pancreatic cancer is unique because it uses a hepatic artery infusion (HAI) pump to deliver chemotherapy directly to the liver. This targeted delivery method aims to maximize the drug's efficacy while minimizing systemic side effects, which is a significant advantage over standard intravenous chemotherapy. Researchers are excited about this treatment because the direct infusion approach has shown promise in managing liver metastases from colorectal cancer, suggesting it might improve outcomes for pancreatic cancer patients as well.

What evidence suggests that Floxuridine via hepatic artery infusion pump might be an effective treatment for pancreatic cancer?

In this trial, participants will receive Floxuridine (FUDR) via a hepatic artery infusion (HAI) pump, which delivers the medicine directly to the liver. Research has shown that using an FUDR pump offers potential benefits for patients with pancreatic cancer that has spread to the liver. In one study, some patients experienced tumor shrinkage, known as a partial response, while others had stable disease without progression. On average, these patients lived for about 11.6 months. This suggests that FUDR can help control liver cancer in some patients. The treatment has been used safely in similar cases where cancer spread to the liver from the colon or rectum. ^{1 6 7 8 9}

Who Is on the Research Team?

G. Paul Wright, MD

Principal Investigator

Corewell Health

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with pancreatic cancer that has spread to the liver. They must have a specific tumor marker level (CA19-9 >37 U/mL), be able to undergo surgery for a chemo pump, and have had at least 2 months of stable disease on standard chemo.

Inclusion Criteria

I have pancreatic cancer that has spread to my liver.

I've had at least 2 months of chemotherapy with no worsening of my cancer.

I can safely undergo general anesthesia and have a pump placed inside me.

Exclusion Criteria

My liver disease is severe, with a MELD score over 20.

My primary tumor has been surgically removed.

My cancer has spread to the lining of my abdomen.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgical Placement and Initial Treatment

Surgical placement of the HAI pump and initial filling with FUDR to start the first cycle

3-5 days

1 hospital stay (3-5 days)

Treatment

Participants receive 6 cycles of FUDR via HAI pump, with each cycle lasting 4 weeks

24 weeks

6 cycles, each with 1 visit for pump refill

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Regular visits every 3 months for imaging studies

What Are the Treatments Tested in This Trial?

Interventions

• Floxuridine (FUDR)
• Hepatic Artery Infusion Pump

Trial Overview The study tests Floxuridine chemotherapy delivered directly into the liver through an infusion pump, alongside standard care. It's a phase II trial without placebo control, aiming to see how well this method works on liver metastases from pancreatic cancer.

How Is the Trial Designed?

Group I: Floxuridine (FUDR) via HAI pump Experimental Treatment 3 Interventions

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.

Who Is Running the Clinical Trial?

Spectrum Health Hospitals

Lead Sponsor

Trials

66

Recruited

553,000+

Published Research Related to This Trial

In a study of 258 patients with pancreatic cancer liver metastases, those receiving hepatic artery infusion (HAI) of floxuridine (FUDR) showed a significantly higher intrahepatic objective response rate (66.1%) compared to those who did not receive HAI (22.6%).

Patients treated with HAI also experienced a longer median overall survival of 14.0 months versus 10.8 months for those without HAI, indicating that HAI FUDR combined with systemic chemotherapy is an effective treatment option for improving outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic Artery Infusion of Floxuridine in Combination With Systemic Chemotherapy for Pancreatic Cancer Liver Metastasis: A Propensity Score-Matched Analysis in Two Centers. Peng, C., Xu, B., Xiao, J., et al.[2022]

In a phase II study involving 23 patients with metastatic pancreatic carcinoma, the combination of 5-fluorouracil, leucovorin, and interferon alpha-2a showed no objective clinical responses, with 14 out of 18 evaluable patients experiencing disease progression.

The treatment was associated with significant toxicity, primarily nausea and vomiting, leading to notable hospitalization rates, indicating that this regimen is ineffective and poses considerable risks even for patients with good performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of 5-fluorouracil, leucovorin, and interferon alpha 2A (IFN-alpha 2a) in metastatic pancreatic carcinoma: a Penn Cancer Clinical Trials Group (PCCTG) trial. David, AK., Vaughn, DJ., Holroyde, CP., et al.[2019]

In a study of 35 patients with locally advanced unresectable pancreatic cancer, those who received adjuvant chemotherapy with doxifluridine (5'-DFUR) after radiotherapy showed significantly improved survival rates compared to those who received radiotherapy alone, with 1-year survival rates of 50% versus 29%.

The addition of 5'-DFUR not only prolonged survival but also delayed tumor marker elevation and improved local control of the disease, indicating its potential as an effective treatment strategy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival benefits of adjuvant chemotherapy with oral doxifluridine (5'-DFUR) following radiotherapy in patients with unresectable pancreatic cancer. Tsuruta, K., Okamoto, A., Egawa, N., et al.[2019]

In a review of 8 randomized controlled trials involving 3,455 patients with advanced gastric cancer, S-1 was associated with fewer severe adverse events compared to 5-fluorouracil (5-FU), particularly showing lower rates of stomatitis, hypokalemia, mucosal inflammation, and hypophosphatemia.

Both S-1 and 5-FU have side effects, but the findings suggest that S-1 may be a safer option for patients, highlighting the need for healthcare providers to monitor and manage adverse events effectively to enhance patient compliance and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

S-1 and 5-Fluorouracil-related adverse events in patients with advanced gastric cancer: A meta-analysis. Hu, Q., Xu, J., Ke, J., et al.[2023]

Modified-FOLFIRINOX (mFOLFIRINOX) significantly improves safety and tolerability for Chinese patients with locally advanced pancreatic cancer (LAPC), with a response rate of 37.1% and common severe side effects including neutropenia and anemia.

Patients with LAPC who received neoadjuvant therapy with mFOLFIRINOX and subsequently underwent surgery had a median overall survival of 27.7 months, which is significantly better than the 8.9 months seen in patients who had upfront surgery without prior chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Modified-FOLFIRINOX-Regimen-Based Neoadjuvant Therapy with Outcomes of Locally Advanced Pancreatic Cancer in Chinese Population. Li, X., Guo, C., Li, Q., et al.[2023]

The combination of doxifluridine (5-DFUR) and radiotherapy improved the chances of surgical resection in patients with locally unresectable pancreatic cancer, achieving a 16% resectability rate in a study of 32 patients.

The median survival time for all patients was 9 months, with a 1-year survival rate of 31%, indicating that this treatment regimen is both feasible and potentially effective, with no severe toxic events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoradiotherapy as preoperative treatment in locally advanced unresectable pancreatic cancer patients: results of a feasibility study. Bajetta, E., Di Bartolomeo, M., Stani, SC., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12161780/

A phase II trial of FUdR in patients with advanced ... Four patients achieved partial response and 16 patients had stable disease. Median survival of patients treated with FUdR was 11.6 months with a range of 3–16 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03856658

NCT03856658 | Hepatic Artery Infusional Floxuridine to ... The purpose is to determine the impact of hepatic artery infusion Floxuridine (FUDR) on liver metastases from pancreatic adenocarcinoma. Patients at Spectrum ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/15449185/

A phase II trial of FUdR in patients with advanced ... Results: Four patients achieved partial response and 16 patients had stable disease. Median survival of patients treated with FUdR was 11.6 months with a range ...

4. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.652426/full

Hepatic Artery Infusion of Floxuridine in Combination With ... We evaluate the efficacy of HAI FUDR via a radiologically implanted pump in patients who had pancreatic cancer liver metastases (PCLM) in two centers.

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-03244

Hepatic Artery Chemotherapy for the Treatment of Patients ... This phase II trial tests the safety, side effects and effectiveness of hepatic artery (HA) chemotherapy with floxuridine (FUDR) and oxaliplatin before surgery ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8113695/

Hepatic Artery Infusion of Floxuridine in Combination With ... Herein, we evaluate the efficacy of HAI FUDR via a radiologically implanted pump in patients who had pancreatic cancer liver metastases (PCLM) ...

7. ctv.veeva.com ctv.veeva.com/study/hepatic-artery-infusional-floxuridine-to-treat-pancreatic-cancer-liver-metastases

Hepatic Artery Infusional Floxuridine to Treat Pancreatic ... This regimen has been utilized with an acceptable safety profile in the setting of colorectal liver metastases. Treatment: Drug: Floxuridine ( ...

8. asco.org asco.org/abstracts-presentations/ABSTRACT435994

Phase II study evaluating the efficacy of PDS0301 in ... Methods: This is a single center, non-randomized Phase II study to determine the safety and efficacy of PDS0301 in combination with floxuridine (FUDR) ...

9. clinicaltrial.be clinicaltrial.be/en/details/64985?per_page=100&only_recruiting=0&only_eligible=0&only_active=0

Hepatic Artery Infusional Floxuridine to Treat Pancreatic... Together the FUDR and the HAI pump are experimental because they are being used to treat hepatic liver metastases of Pancreatic adenocarcinoma.