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

14 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new way to treat pancreatic cancer that has spread to the liver. Patients will receive a special chemotherapy drug directly into their liver through a pump, along with their usual chemotherapy. The goal is to see if this method helps them live longer.

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.

What data supports the effectiveness of the drug Floxuridine (FUDR) for pancreatic cancer?

Research shows that using Floxuridine (FUDR) through the hepatic artery, combined with other chemotherapy, can be effective for treating liver metastases from pancreatic cancer. Additionally, a study found that Floxuridine with dexamethasone improved tumor response in colorectal cancer, suggesting potential benefits in similar treatments. ^{1 2 3 4 5}

Is Floxuridine (FUDR) generally safe for humans?

Floxuridine (FUDR) has been studied for safety in humans, with common side effects including gastrointestinal issues like nausea, vomiting, and diarrhea. In some cases, lung toxicity has been reported, but it is rare. The safety of FUDR depends on the dose, with higher doses leading to more side effects. ^{2 6 7 8 9}

How is the drug Floxuridine unique for treating pancreatic cancer?

Floxuridine is unique for treating pancreatic cancer because it is administered directly into the liver through hepatic artery infusion (HAI), which allows for higher concentrations of the drug to target liver metastases specifically, potentially improving its effectiveness compared to standard systemic chemotherapy. ^{1 5 10 11 12}

Research Team

G. Paul Wright, MD

Principal Investigator

Corewell Health

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

References

1. Switzerland 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. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

A phase II trial of FUdR in patients with advanced pancreatic cancer. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Association of Modified-FOLFIRINOX-Regimen-Based Neoadjuvant Therapy with Outcomes of Locally Advanced Pancreatic Cancer in Chinese Population. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Hepatic artery dexamethasone infusion inhibits colorectal hepatic metastases: a regional antiangiogenic therapy. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Treatment of advanced adenocarcinomas of the exocrine pancreas and the gallbladder with 5-fluorouracil, high dose levofolinic acid and oral hydroxyurea on a weekly schedule. Results of a multicenter study of the Southern Italy Oncology Group (G.O.I.M.). [2013]

6. United States 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. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

S-1 and 5-Fluorouracil-related adverse events in patients with advanced gastric cancer: A meta-analysis. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Steroid-responsive interstitial lung disease in patients receiving 2'-deoxy-5-fluorouridine-infusion chemotherapy. A report of three cases. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Phase I study of continuous venous infusion of floxuridine (5-FUDR) chemotherapy. [2013]

10. United States pubmed.ncbi.nlm.nih.gov

Chemoradiotherapy as preoperative treatment in locally advanced unresectable pancreatic cancer patients: results of a feasibility study. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Survival benefits of adjuvant chemotherapy with oral doxifluridine (5'-DFUR) following radiotherapy in patients with unresectable pancreatic cancer. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

A phase II study of combination therapy with 5'-deoxy-5-fluorouridine and cisplatin in the treatment of advanced gastric cancer with primary foci. [2019]