Liposomal Irinotecan + FOLFOX for Pancreatic Cancer

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

45 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Liposomal Irinotecan + FOLFOX for treating pancreatic cancer?

Research shows that liposomal irinotecan combined with 5-fluorouracil and leucovorin significantly improved survival in patients with metastatic pancreatic cancer compared to 5-fluorouracil and leucovorin alone, with a 45% increase in median overall survival. ^{1 2 3 4 5}

Is the combination of Liposomal Irinotecan and FOLFOX safe for treating pancreatic cancer?

The combination of Liposomal Irinotecan and 5-fluorouracil (5-FU) has been shown to be effective and generally well-tolerated in patients with advanced pancreatic cancer, although some patients may experience significant blood-related side effects. Modified versions of similar treatments have been developed to improve safety by reducing certain toxicities. ^{1 6 7 8 9}

What makes the drug Liposomal Irinotecan + FOLFOX unique for treating pancreatic cancer?

Liposomal Irinotecan + FOLFOX is unique because it uses a special formulation of irinotecan encapsulated in a lipid layer, which helps improve its effectiveness and safety compared to the non-liposomal version. This drug combination is particularly beneficial for patients with metastatic pancreatic cancer who have already been treated with gemcitabine-based therapies, offering a new option when other treatments have failed. ^{3 5 10 11 12}

What is the purpose of this trial?

This is a phase II, single arm, non-randomized, open label study of liposomal irinotecan with FOLFOX in the neoadjuvant setting in patients with resectable or borderline resectable, previously untreated pancreatic adenocarcinoma. The primary objective of this study is to investigate the safety and feasibility of this treatment regimen in this patient population.

Research Team

Thomas George, MD

Principal Investigator

University of Florida

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

References

1. England 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Survival with nal-IRI (liposomal irinotecan) plus 5-fluorouracil and leucovorin versus 5-fluorouracil and leucovorin in per-protocol and non-per-protocol populations of NAPOLI-1: Expanded analysis of a global phase 3 trial. [2022]

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

NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: Final overall survival analysis and characteristics of long-term survivors. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Liposomal irinotecan plus fluorouracil/leucovorin versus FOLFIRINOX as the second-line chemotherapy for patients with metastatic pancreatic cancer: a multicenter retrospective study of the Korean Cancer Study Group (KCSG). [2021]

5. Japan pubmed.ncbi.nlm.nih.gov

Effect of previous conventional irinotecan treatment in patients with pancreatic cancer being treated with liposomal irinotecan plus 5-fluorouracil and leucovorin. [2023]

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

Modified FOLFIRINOX regimen with improved safety and maintained efficacy in pancreatic adenocarcinoma. [2022]

7. England pubmed.ncbi.nlm.nih.gov

The Impact of Liposomal Irinotecan on the Treatment of Advanced Pancreatic Adenocarcinoma: Real-World Experience in a Taiwanese Cohort. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Gemcitabine, oxaliplatin and weekly high-dose 5-FU as 24-h infusion in chemonaive patients with advanced or metastatic pancreatic adenocarcinoma: a multicenter phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO). [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Modified FOLFIRINOX for Advanced Pancreatic Adenocarcinoma: A UK Single-Centre Experience. [2023]

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

Liposomal Irinotecan: A Review in Metastatic Pancreatic Adenocarcinoma. [2023]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Prolonged response to liposomal irinotecan in a patient with stage IV pancreatic/bile duct cancer previously treated with FOLFIRINOX and gemcitabine plus nab-paclitaxel. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. [2022]