Hepatic Artery Chemotherapy for Pancreatic Cancer

Overseen By Adi Molvin, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Duke University

Must be taking: FOLFIRINOX

Must not be taking: Systemic corticosteroids

Disqualifiers: Liver cirrhosis, Active hepatitis, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 32

Duration: 2 weeks

20 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on chronic systemic corticosteroids or immunosuppressive medications, you may need to adjust your treatment. It's best to discuss your specific medications with the trial team.

What data supports the idea that Hepatic Artery Chemotherapy for Pancreatic Cancer is an effective treatment?

The available research shows that Hepatic Artery Chemotherapy (HA Chemotherapy) is being studied for its effectiveness in treating pancreatic cancer that has spread to the liver. One study specifically looked at using a drug called floxuridine (FUDR) with other chemotherapy drugs for this purpose. While the research primarily focuses on liver metastases from colorectal cancer, it suggests that HA Chemotherapy could be beneficial for pancreatic cancer as well. This treatment is considered effective for liver metastases from colorectal cancer, which indicates potential for similar success in pancreatic cancer cases. ^{1 2 3 4 5}

What safety data exists for hepatic artery chemotherapy in pancreatic cancer?

The safety of hepatic artery infusion (HAI) chemotherapy for pancreatic cancer has been evaluated in several studies. One study assessed HAI chemotherapy after pancreatectomy for pancreatobiliary cancer, focusing on safety. Another study reported on HAI of floxuridine combined with systemic chemotherapy for pancreatic cancer liver metastases, noting that while there were some hematologic adverse events like leukocytopenia and anemia, no life-threatening toxicities were observed. However, catheter complications were common. Overall, HAI chemotherapy is considered useful and safe for treating liver-confined malignancies, with increased regional efficacy and lower systemic side effects. ^{1 6 7 8 9}

Is the treatment HA Chemotherapy a promising treatment for pancreatic cancer?

Yes, HA Chemotherapy, which involves delivering drugs directly to the liver, shows promise for treating pancreatic cancer that has spread to the liver. It has been effective in treating liver metastases from other cancers, like colorectal cancer, and is being tested for pancreatic cancer with positive results. ^{1 2 4 10 11}

What is the purpose of this trial?

This is a window-of-opportunity study which will evaluate the safety and feasibility of single-dose neoadjuvant Hepatic Artery (HA) chemotherapy (FUDR/oxaliplatin) in patients with localized pancreatic ductal adenocarcinoma (PDAC) eligible for surgical resection and systemic chemotherapy. Current standard-of-care therapy for patients with localized PDAC includes surgical resection and six months of systemic chemotherapy. Because the sequence of these treatments (surgery and chemotherapy) is not well established, we will include both patients planned to undergo surgery before chemotherapy, as well as patients planned to receive systemic chemotherapy before surgery. This will allow us to test the safety and feasibility of adding single-dose neoadjuvant HA chemotherapy prior to surgery across the real-world treatment strategies employed in typical clinical practice. Moreover, the window-of-opportunity design is intended to make sure that all patients receive HA chemotherapy in addition to standard-of-care surgery and systemic chemotherapy, so as not to withhold the treatment approach currently associated with best outcomes. The primary endpoint is safety and feasibility, and patients will be followed for 30 days after resection of their primary tumors to assess these outcomes. Following the short-term follow-up period, patients move to long-term follow-up, which will occur every three months after resection of the primary tumor, for a period of up to three years. Long-term secondary endpoints include disease free survival (DFS), liver metastasis-free survival (LMFS), and overall survival (OS).

Research Team

Daniel Nussbaum, MD

Principal Investigator

Duke Medical Center

Eligibility Criteria

This trial is for adults over 18 with localized pancreatic cancer who are fit (ECOG 0-1) and eligible for surgery and chemotherapy. They must have good organ function, agree to use contraception if fertile, and not be pregnant or breastfeeding. Exclusions include recent major surgeries, other interventional trials participation during the study period, severe medical conditions, liver cirrhosis, high CA 19-9 levels before surgery, history of certain cancers within two years or prior liver surgery.

Inclusion Criteria

I am using birth control and my pregnancy test was negative.

My doctor has approved me for FOLFIRINOX treatment.

My blood tests and organ functions are within normal ranges.

Exclusion Criteria

I do not have any severe or uncontrolled health conditions.

I have a serious wound or fracture that is not healing.

I have hepatitis B or C.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

0 to 4 weeks

1 visit (in-person)

Treatment

Participants receive neoadjuvant HA chemotherapy and undergo standard-of-care diagnostic laparoscopy and tumor resection

2 weeks

Multiple visits (in-person) including Day 1 laparoscopy, Day 2 chemotherapy, and Day 14 tumor resection

Short-term Follow-up

Participants are monitored for safety and feasibility outcomes for 30 days post-operatively

4 weeks

Outpatient follow-up at 30 days post-surgery

Long-term Follow-up

Participants are monitored every three months for disease-free survival, liver metastasis-free survival, and overall survival

Up to 3 years

Quarterly visits (in-person)

Treatment Details

Interventions

• HA Chemotherapy

Trial Overview The trial tests single-dose neoadjuvant Hepatic Artery (HA) chemotherapy using FUDR/oxaliplatin in patients with pancreatic cancer scheduled for resection and systemic chemo. It aims to determine the safety of adding HA chemo before standard treatments across different treatment sequences. Patients will be monitored short-term post-surgery then every three months up to three years for survival outcomes.

Participant Groups

Group I: PDAC with HA Chemotherapy Experimental Treatment 1 Intervention

Patients eligible to receive systemic chemotherapy and surgical resection will have the investigational treatment, which is neoadjuvant HA chemotherapy prior to resection.

HA Chemotherapy is already approved in United States for the following indications:

Approved in United States as FUDR/Oxaliplatin for:

• Colorectal cancer liver metastases
• Unresectable colorectal cancer

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

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]

In a study of 21 heavily pre-treated patients with liver metastases from colorectal cancer, hepatic arterial chemotherapy using oxaliplatin, folinic acid, and 5-fluorouracil showed a median overall survival of 36.1 months, with 62% and 52% survival rates at 2 and 3 years, respectively.

The treatment was feasible with low toxicity, where the main side effects included pain and transaminase elevation, and it resulted in tumor growth control in 52% of patients, indicating its potential as a viable option for those who have undergone multiple prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic arterial chemotherapy with oxaliplatin, folinic acid and 5-fluorouracil in pre-treated patients with liver metastases from colorectal cancer. Del Freo, A., Fiorentini, G., Sanguinetti, F., et al.[2022]

In a study involving 61 patients with advanced cancer primarily affecting the liver, hepatic arterial infusion (HAI) of oxaliplatin combined with capecitabine and bevacizumab showed promising results, with a 22% partial response rate and a median overall survival of 6.9 months for those receiving bevacizumab.

The treatment was generally well-tolerated, with the maximum tolerated doses identified as HAI oxaliplatin 140 mg/m2, capecitabine 750 mg/m2, and bevacizumab 10 mg/kg, although some patients experienced significant side effects like Grade 3 diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I clinical trial of hepatic arterial infusion of oxaliplatin and oral capecitabine, with or without intravenous bevacizumab, in patients with advanced cancer and predominant liver involvement. Fountzilas, E., Krishnan, E., Janku, F., et al.[2019]

In a review of 47 studies on hepatic artery infusion (HAI) for unresectable colorectal liver metastases, the fully implantable pump was associated with the lowest complication rate (15.8%) compared to surgical (34%) and radiological catheters (36.1%).

The fully implantable pump also allowed for a higher median number of chemotherapy cycles (12 cycles) compared to 8 cycles with surgical catheters and 6 cycles with radiological catheters, indicating its efficacy in delivering loco-regional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-arterial hepatic chemotherapy for unresectable colorectal liver metastases: a review of medical devices complications in 3172 patients. Bacchetti, S., Pasqual, E., Crozzolo, E., et al.[2021]

A study involving 170 patients with liver tumors and pancreatic or bile duct cancer successfully demonstrated a new technique for placing intra-arterial catheters using a transcutaneous subclavian access, eliminating the need for laparotomy.

While there were some complications, including 5 cases of subclavian artery aneurysms and 9 hepatic artery thromboses, the overall success rate of the procedure suggests that this method could expand the use of regional chemotherapy for various hepatic tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous implantation of arterial Port-a-cath via trans-subclavin access. Zanon, C., Grosso, M., Clara, R., et al.[2004]

Hepatic arterial infusion (HAI) chemotherapy after pancreatectomy is feasible and generally safe, with a successful catheter-port system placement in all 51 patients studied, although complications like hepatic artery stenosis occurred in 19.6% of cases.

The study found a tumor response rate of 44.4% for liver metastases treated with HAI chemotherapy, indicating its potential efficacy, especially considering the low hepatic recurrence rate of 7.1% with adjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and optimal management of hepatic arterial infusion chemotherapy after pancreatectomy for pancreatobiliary cancer. Hashimoto, A., Nishiofuku, H., Tanaka, T., et al.[2013]

In a phase III trial involving 262 patients with advanced hepatocellular carcinoma (HCC), hepatic arterial infusion chemotherapy (HAIC-FO) significantly improved overall survival (OS) compared to sorafenib, with median OS of 13.9 months for HAIC-FO versus 8.2 months for sorafenib.

HAIC-FO also demonstrated tumor downstaging in 12.3% of patients, leading to a median OS of 20.8 months for those who underwent curative surgery or ablation, highlighting its potential effectiveness even in patients with high disease burden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Arterial Chemotherapy of Oxaliplatin Plus Fluorouracil Versus Sorafenib in Advanced Hepatocellular Carcinoma: A Biomolecular Exploratory, Randomized, Phase III Trial (FOHAIC-1). Lyu, N., Wang, X., Li, JB., et al.[2022]

In a study of 41 patients with advanced hepatocellular carcinoma (HCC), repetitive hepatic arterial infusion chemotherapy (HAIC) using high-dose 5-fluorouracil and cisplatin resulted in a partial response in 22% of patients and stable disease in 34%, indicating its efficacy as a treatment option.

The median overall survival for patients who achieved disease control was significantly longer at 14 months compared to 6 months for those with disease progression, suggesting that HAIC can improve survival outcomes in advanced HCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive short-course hepatic arterial infusion chemotherapy with high-dose 5-fluorouracil and cisplatin in patients with advanced hepatocellular carcinoma. Park, JY., Ahn, SH., Yoon, YJ., et al.[2022]

In a pilot study involving 5 patients with liver metastases from pancreatic cancer, hepatic arterial infusion (HAI) chemotherapy using gemcitabine and 5-fluorouracil resulted in a 100% response rate, with 2 patients showing partial response and 3 achieving stable disease.

HAI chemotherapy demonstrated a decrease in the tumor marker CA19-9 in 4 out of 5 patients, and while there were some hematologic side effects, no severe non-hematologic toxicities were reported, indicating that HAI is a promising and safe treatment option for liver-confined malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of hepatic arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for patients with postoperative liver metastases from pancreatic cancer. Tajima, H., Ohta, T., Kitagawa, H., et al.[2022]

Hepatic artery infusion chemotherapy is becoming more popular for treating nonresectable liver cancer, but understanding the liver's arterial blood supply is crucial for effective treatment.

A review of 70 hepatic artery angiograms highlighted the importance of accurate anatomical knowledge to ensure proper liver perfusion and avoid affecting other organs during chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic artery infusion: surgical approach. Albano, WA., Durr, M., Gutierrez, AR., et al.[2019]

Hepatic artery infusion chemotherapy can lead to serious complications, including gastric perforation, as demonstrated in a reported case.

The study highlights how variations in hepatic artery branching and catheter placement can contribute to the risk of such life-threatening complications during this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastric perforation from hepatic artery infusion chemotherapy. Choplin, RH., Gelfand, DW., Hunt, TH.[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. Greece pubmed.ncbi.nlm.nih.gov

Hepatic arterial chemotherapy with oxaliplatin, folinic acid and 5-fluorouracil in pre-treated patients with liver metastases from colorectal cancer. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

A phase I clinical trial of hepatic arterial infusion of oxaliplatin and oral capecitabine, with or without intravenous bevacizumab, in patients with advanced cancer and predominant liver involvement. [2019]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Intra-arterial hepatic chemotherapy for unresectable colorectal liver metastases: a review of medical devices complications in 3172 patients. [2021]

5. Greece pubmed.ncbi.nlm.nih.gov

Percutaneous implantation of arterial Port-a-cath via trans-subclavin access. [2004]

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

Safety and optimal management of hepatic arterial infusion chemotherapy after pancreatectomy for pancreatobiliary cancer. [2013]

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

Arterial Chemotherapy of Oxaliplatin Plus Fluorouracil Versus Sorafenib in Advanced Hepatocellular Carcinoma: A Biomolecular Exploratory, Randomized, Phase III Trial (FOHAIC-1). [2022]

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

Repetitive short-course hepatic arterial infusion chemotherapy with high-dose 5-fluorouracil and cisplatin in patients with advanced hepatocellular carcinoma. [2022]

9. Greece pubmed.ncbi.nlm.nih.gov

Pilot study of hepatic arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for patients with postoperative liver metastases from pancreatic cancer. [2022]

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

Hepatic artery infusion: surgical approach. [2019]

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

Gastric perforation from hepatic artery infusion chemotherapy. [2019]