Liposomal Irinotecan + FOLFOX for Pancreatic Cancer

Not currently recruiting at 3 trial locations

Overseen By Alexandra Mueller

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Florida

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Metastatic disease, Other malignancy, 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

Compensation: Varies

Number of Visits: 8

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with newly diagnosed pancreatic cancer that can potentially be removed by surgery. The goal is to determine if this combination is safe and practical before surgery. The trial uses liposomal irinotecan (a type of chemotherapy) with FOLFOX, which includes 5-FU (fluorouracil, a chemotherapy drug), oxaliplatin (a platinum-based chemotherapy), and liposomal irinotecan. Individuals diagnosed with pancreatic cancer that has not spread and have not received prior treatment may be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires that you stop using strong CYP3A4 inhibitors or inducers before joining. If you're on these medications, you'll need to discuss with your doctor about stopping them.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that liposomal irinotecan, when combined with 5-FU and oxaliplatin, is generally well-tolerated by patients. While some may experience side effects, they are usually manageable. Common side effects include nausea, diarrhea, and fatigue.

One study found that this combination did not cause any unexpected safety issues. Another study confirmed that this treatment is safe and can be used before surgery in pancreatic cancer patients.

Overall, evidence suggests that this treatment is safe for most people, although individual experiences may vary. Prospective trial participants should discuss possible side effects with their doctor to make an informed decision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Liposomal irinotecan with FOLFOX is unique because it combines a new delivery method with existing chemotherapy agents to potentially enhance treatment for pancreatic cancer. While the standard of care often involves gemcitabine-based regimens, this treatment uses liposomal technology to deliver irinotecan more effectively, potentially increasing its impact on cancer cells while minimizing side effects. Researchers are excited because this approach could improve the drug's ability to penetrate tumors, offering a new hope for better outcomes in a challenging-to-treat cancer.

What evidence suggests that this treatment might be an effective treatment for pancreatic cancer?

Research has shown that a combination of liposomal irinotecan and FOLFOX, which participants in this trial will receive, may help treat pancreatic cancer. In one study, patients experienced a median progression-free survival of about 8.11 months, meaning their cancer did not worsen for over 8 months on average. Liposomal irinotecan is designed to remain in the body longer, potentially making it more effective than regular irinotecan. When combined with FOLFOX, which includes drugs like 5-FU and oxaliplatin, it aims to better target cancer cells. Early results suggest this combination could be a promising option for people with pancreatic cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

Thomas George, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

Adults with a new diagnosis of resectable or borderline resectable, untreated pancreatic adenocarcinoma. Participants must have good performance status, treated biliary obstruction if present, no metastatic disease, and adequate organ function. Women and men must use effective contraception.

Inclusion Criteria

My cancer has not spread to other parts of my body.

I have been tested for Gilbert's syndrome before starting treatment.

My bile duct blockage has been treated.

Exclusion Criteria

My cancer cannot be surgically removed or has spread to other parts of my body.

Presence of any known contraindications to or hypersensitivities to the investigational products

I have received treatment for pancreatic cancer before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive liposomal irinotecan with FOLFOX in 8 cycles, each cycle lasting 14 days

16 weeks

8 visits (in-person)

Surgery

Participants undergo surgical resection to achieve complete surgical resection (R0)

1 week

Follow-up

Participants are monitored for post-operative complications and overall response rate

9 months

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• 5-FU
• Liposomal Irinotecan
• Oxaliplatin

Trial Overview The trial is testing the combination of Liposomal Irinotecan with FOLFOX (a chemo regimen) as a preoperative treatment for pancreatic cancer. It's an open-label study where all participants receive the same treatment to assess safety and feasibility.

How Is the Trial Designed?

Group I: Liposomal irinotecan with FOLFOX Experimental Treatment 2 Interventions

Subjects will receive 8 cycles and each cycle is 14 days.

5-FU is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Approved in European Union as Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Skin cancer

Approved in Canada as Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Approved in Japan as Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Ipsen

Industry Sponsor

Trials

358

Recruited

74,600+

David Loew

Ipsen

Chief Executive Officer since 2020

BA in Business Administration and MBA from the University of St. Gallen, Switzerland

Sandra Silvestri

Ipsen

Chief Medical Officer since 2023

MD, PhD

Published Research Related to This Trial

The modified FOLFIRINOX (mFOLFIRINOX) regimen showed a tolerable safety profile with lower hematological toxicity compared to the full-dose FOLFIRINOX, while still maintaining comparable efficacy in treating advanced pancreatic ductal adenocarcinoma (PDAC).

In a study of 18 patients, 80% achieved at least stable disease, with a median overall survival of 9.3 months and progression-free survival of 7.2 months, indicating that mFOLFIRINOX can be an effective treatment option for fit patients with advanced PDAC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Modified FOLFIRINOX for Advanced Pancreatic Adenocarcinoma: A UK Single-Centre Experience. Ghorani, E., Wong, HH., Hewitt, C., et al.[2023]

Modified FOLFIRINOX, which eliminates bolus 5-FU, shows an improved safety profile with low rates of severe side effects, such as only 3% experiencing grade 4 neutropenia, while maintaining efficacy in treating pancreatic cancer.

In patients with nonmetastatic pancreatic cancer, modified FOLFIRINOX resulted in a median overall survival of 17.8 months and a median progression-free survival of 13.7 months, indicating promising activity in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified FOLFIRINOX regimen with improved safety and maintained efficacy in pancreatic adenocarcinoma. Mahaseth, H., Brutcher, E., Kauh, J., et al.[2022]

In the phase III NAPOLI-1 trial, liposomal irinotecan combined with 5-fluorouracil and leucovorin significantly improved median overall survival and progression-free survival in patients with metastatic pancreatic adenocarcinoma after gemcitabine therapy, indicating its efficacy as a treatment option.

The combination therapy had a manageable safety profile, with the most common severe side effects being related to blood and gastrointestinal issues, and a low incidence of neutropenic sepsis, making it a safer alternative in a challenging treatment landscape.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal Irinotecan: A Review in Metastatic Pancreatic Adenocarcinoma. Lamb, YN., Scott, LJ.[2023]

In a real-world study of 86 patients with metastatic pancreatic adenocarcinoma who received nal-IRI plus 5-FU/LV after gemcitabine therapy, the median overall survival was 9.4 months, indicating that this treatment is effective in this patient population.

The treatment was generally well-tolerated, with the most common severe side effects being neutropenia (37.2%) and nausea (10.5%), suggesting a manageable safety profile similar to findings from the NAPOLI-1 trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world efficacy and safety of liposomal irinotecan plus fluorouracil/leucovorin in patients with metastatic pancreatic adenocarcinoma: a study by the Korean Cancer Study Group. Yoo, C., Im, HS., Kim, KP., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/OA-25-00047

Phase II Study of Liposomal Irinotecan in Combination With ... The median progression-free survival was 8.11 months (95% CI, 5.19 to 12.1). The observed AEs associated with study treatment were consistent ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10594143/

A phase II study of neoadjuvant liposomal irinotecan with 5 ... The treatment for pancreatic adenocarcinoma is constantly evolving with improved outcomes needed. Neoadjuvant therapy is recommended for many ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03861702

Liposomal Irinotecan in Combination With Oxaliplatin ... This is a phase II, single-arm, open-label, clinical study to investigate the efficacy and tolerability of a combination of liposomal irinotecan (nal-IRI) with ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0959804921001957

First-line liposomal irinotecan with oxaliplatin, 5- ... This open-label, phase I/II study evaluated safety and efficacy for first-line liposomal irinotecan + oxaliplatin + 5-fluorouracil + leucovorin (NALIRIFOX).

5. esmoopen.com esmoopen.com/article/S2059-7029(21)00003-X/pdf

Liposomal irinotecan plus fluorouracil/leucovorin versus ... This retrospective, multicenter (11 tertiary referral centers) study was conducted by the hepatobiliary and pancreatic cancer division of the ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37753702/

A phase II study of neoadjuvant liposomal irinotecan with 5-FU ... This investigation explores the safety and feasibility of substituting liposomal irinotecan (nal-IRI) for nonliposomal irinotecan to improve tumor drug ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03483038

NCT03483038 | A Study of the Safety and Activity ... A Study of the Safety and Activity of Liposomal Irinotecan in Combination With the 5-FU and Oxaliplatin in the Preoperative Treatment of Pancreatic ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33957442/

First-line liposomal irinotecan with oxaliplatin, 5- ... This open-label, phase I/II study evaluated safety and efficacy for first-line liposomal irinotecan + oxaliplatin + 5-fluorouracil + leucovorin (NALIRIFOX).

9. bmcmedicine.biomedcentral.com bmcmedicine.biomedcentral.com/articles/10.1186/s12916-025-04234-4

Phase 1 trial of HR070803 (an Irinotecan liposome) in ... This study assessed the safety, preliminary antitumor activity, and pharmacokinetics of HR070803 (a novel liposomal irinotecan) in combination with 5-FU/LV and ...