NALIRIFOX for Pancreatic Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Roswell Park Cancer Institute

Disqualifiers: Previous chemotherapy, Metastatic PDAC, UGT1A1 polymorphisms, 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: 3

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug NALIRIFOX for pancreatic cancer?

The NAPOLI 3 trial compared NALIRIFOX to another treatment (nab-paclitaxel and gemcitabine) for pancreatic cancer, suggesting it is being actively studied for its effectiveness. Additionally, FOLFIRINOX, a similar treatment, has shown improved outcomes in pancreatic cancer, indicating potential effectiveness for NALIRIFOX. ^{1 2 3 4 5}

How is the drug NALIRIFOX different from other treatments for pancreatic cancer?

NALIRIFOX is a combination treatment that includes irinotecan liposome, fluorouracil, leucovorin, and oxaliplatin, and it is being compared to the standard treatment of nab-paclitaxel and gemcitabine for metastatic pancreatic cancer. This combination aims to improve efficacy and safety as a first-line therapy, offering a potentially more effective option for patients with this aggressive cancer. ^{1 2 3 6 7}

What is the purpose of this trial?

This phase II trial tests how well liposomal irinotecan, oxaliplatin, 5-fluorouracil and leucovorin (NALIRIFOX) before surgery works in treating patients with pancreatic ductal adenocarcinoma that is close to major blood vessels, but is still potentially removable by surgery (borderline resectable). Irinotecan is in a class of antineoplastic medications called topoisomerase I inhibitors. It blocks a certain enzyme needed for cell division and deoxyribonucleic acid (DNA) repair and may kill tumor cells. Liposomal irinotecan is a form of the anticancer drug irinotecan that is contained inside very tiny, fat-like particles. Liposomal irinotecan may have fewer side effects and work better than other forms of the drug. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It damages the cell's DNA and may kill tumor cells. 5-fluorouracil, a type of antimetabolite, stops cells from making DNA and it may kill tumor cells. Leucovorin, a form of folic acid, is used to lessen the toxic effects of substances that block the action of folic acid. It is a type of chemoprotective agent and a type of chemosensitizing agent. Giving NALIRIFOX before surgery may improve the chance of successful surgery and decrease the chance of the cancer returning after surgery in patients with borderline resectable pancreatic ductal adenocarcinoma.

Research Team

Christos Fountzilas

Principal Investigator

Roswell Park Cancer Institute

Eligibility Criteria

This trial is for patients with pancreatic ductal adenocarcinoma that's near major blood vessels but might still be removed surgically. Participants should meet specific health criteria and not have conditions that exclude them, which are not detailed here.

Inclusion Criteria

Platelet count ≥ 100,000 cells/uL

Hemoglobin ≥ 9 g/dL

Plasma albumin ≥ 3 g/dL

Exclusion Criteria

Unwilling or unable to follow protocol requirements

Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug

I am currently pregnant or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive liposomal irinotecan, oxaliplatin, leucovorin, and fluorouracil every 14 days for 4-8 cycles

8-16 weeks

Bi-weekly visits for treatment administration

Surgical Resection

Participants undergo surgical resection 4-8 weeks after the last treatment dose

4-8 weeks

Adjuvant Treatment

Starting 4-12 weeks after surgery, participants receive additional cycles of liposomal irinotecan, oxaliplatin, leucovorin, and fluorouracil

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Every 3-6 months for 2 years, then every 6-12 months

Treatment Details

Interventions

• NALIRIFOX

Trial Overview The NALIRIFOX regimen (liposomal irinotecan, oxaliplatin, fluorouracil, leucovorin) is being tested to see if giving it before surgery can increase the success of removing the tumor and reduce cancer recurrence in borderline resectable pancreatic cancer.

Participant Groups

Group I: Treatment (NALIRIFOX) Experimental Treatment 7 Interventions

Patients receive liposomal irinotecan IV over 90 minutes, oxaliplatin IV over 120 minutes, leucovorin IV over 30 minutes and fluorouracil IV over 48 hours on day 1 of each cycle. Cycles repeat every 14 days for 4-8 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo surgical resection 4-8 weeks after the last treatment dose. Starting 4-12 weeks after surgery, patients receive liposomal irinotecan, oxaliplatin, leucovorin, and fluorouracil for up to 4 additional cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT and blood sample collection throughout the study.

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

Findings from Research

In the NAPOLI 3 study involving 770 patients with metastatic pancreatic ductal adenocarcinoma, the NALIRIFOX treatment regimen resulted in a median overall survival of 11.1 months, which was significantly longer than the 9.2 months observed with the nab-paclitaxel and gemcitabine combination.

Both treatment groups experienced a high rate of grade 3 or higher adverse events (87% for NALIRIFOX and 86% for nab-paclitaxel-gemcitabine), indicating that while NALIRIFOX may improve survival, it does not significantly increase the risk of severe side effects compared to the standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. Wainberg, ZA., Melisi, D., Macarulla, T., et al.[2023]

In a study of 49 patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDA) treated with FOLFIRINOX, the overall response rate was 41%, with a median overall survival of 18.4 months for locally advanced cases and 12.2 months for metastatic cases, indicating significant efficacy of the treatment.

The treatment was associated with notable toxicities, including neutropenia (29%) and fatigue (18%), but careful patient selection and monitoring of biomarkers like CA 19-9 can help improve outcomes and manage risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX for locally advanced or metastatic pancreatic ductal adenocarcinoma: the Royal Marsden experience. Moorcraft, SY., Khan, K., Peckitt, C., et al.[2022]

In a pilot study of 14 patients with resectable pancreatic cancer, treatment with 4 cycles of neoadjuvant FOLFIRINOX resulted in varying degrees of tumor regression, with 28.6% of patients showing significant tumor destruction (Evans grade III).

The study highlights the heterogeneity of pancreatic cancer responses to FOLFIRINOX, indicating that while some patients benefit significantly, others do not, suggesting the need for further research on optimal treatment duration and standardized grading for better comparison.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathologic Response to Primary Systemic Therapy With FOLFIRINOX in Patients With Resectable Pancreatic Cancer. Polish, A., Joseph, NE., Marsh, RW.[2020]

In a study of 46 patients with resectable pancreatic ductal adenocarcinoma (PDAC) treated with modified FOLFIRINOX, pharmacokinetic-guided dosing of 5-Fluorouracil (5-FU) and Irinotecan (CPT-11) was associated with significantly longer progression-free survival.

Patients with a 5-FU area under the curve (AUC) above 28 mcg·h/mL and CPT-11 AUC below 10 mcg·h/mL had a reduced risk of disease progression, suggesting that tailored chemotherapy dosing can enhance treatment efficacy in PDAC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic drug monitoring of neoadjuvant mFOLFIRINOX in resected pancreatic ductal adenocarcinoma. Vilalta-Lacarra, A., Aldaz, A., Sala-Elarre, P., et al.[2023]

Modified-dose FOLFIRINOX (mFOLFIRINOX) demonstrated comparable efficacy to standard-dose FOLFIRINOX (sFOLFIRINOX) in treating pancreatic cancer, with similar objective response rates and overall survival outcomes among 130 patients studied.

mFOLFIRINOX was associated with significantly lower rates of severe adverse events, such as neutropenia, anorexia, and diarrhea, suggesting it is a safer option for patients who may be concerned about toxicity while maintaining effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer. Kang, H., Jo, JH., Lee, HS., et al.[2022]

In a study of 25 patients with borderline resectable or locally unresectable pancreatic cancer, FOLFIRINOX treatment led to a 33% R0 resection rate, indicating successful surgical removal of tumors after neoadjuvant therapy.

The regimen showed promising biological activity, with 24% of patients achieving significant pathologic responses, suggesting that FOLFIRINOX could be an effective neoadjuvant treatment option for this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes with FOLFIRINOX for borderline resectable and locally unresectable pancreatic cancer. Boone, BA., Steve, J., Krasinskas, AM., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. [2023]

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

FOLFIRINOX for locally advanced or metastatic pancreatic ductal adenocarcinoma: the Royal Marsden experience. [2022]

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

Pathologic Response to Primary Systemic Therapy With FOLFIRINOX in Patients With Resectable Pancreatic Cancer. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Therapeutic drug monitoring of neoadjuvant mFOLFIRINOX in resected pancreatic ductal adenocarcinoma. [2023]

5. China pubmed.ncbi.nlm.nih.gov

Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer. [2022]

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

Sintilimab Plus Modified FOLFIRINOX in Metastatic or Recurrent Pancreatic Cancer: The Randomized Phase II CISPD3 Trial. [2023]

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

Outcomes with FOLFIRINOX for borderline resectable and locally unresectable pancreatic cancer. [2022]