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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called NALIRIFOX to evaluate its effectiveness for people with a specific type of pancreatic cancer near major blood vessels but potentially removable with surgery. NALIRIFOX combines drugs that aim to shrink tumors before surgery, making them easier to remove and less likely to return. The trial seeks participants diagnosed with this type of cancer who have not received prior chemotherapy or radiation for it. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer treatment.

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.

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

Research has shown that the NALIRIFOX treatment, which includes a mix of specific cancer-fighting drugs, has been tested for safety in people. In one study, this combination served as an initial treatment and was generally well-tolerated. Some patients experienced side effects common with chemotherapy, such as nausea, diarrhea, and tiredness, but serious side effects were less common.

The special form of one of the drugs in NALIRIFOX is designed to cause fewer side effects than the regular version. This design may make it easier on the body while still effectively fighting cancer. While these results are encouraging, they come from early studies, and individual experiences can differ. Always consult a doctor about potential risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pancreatic cancer?

Researchers are excited about NALIRIFOX for pancreatic cancer because it offers a fresh approach to treatment by combining liposomal irinotecan, oxaliplatin, leucovorin, and fluorouracil in a unique regimen. Unlike standard treatments like FOLFIRINOX or gemcitabine-based therapies, NALIRIFOX uses a liposomal formulation of irinotecan, which enhances drug delivery to cancer cells and may reduce side effects. The treatment is also notable for its structured cycle, with an intensive initial phase followed by surgery and additional cycles, potentially improving outcomes by tackling the cancer more aggressively. This multi-step approach may lead to better control over tumor progression and could provide new hope for patients with this challenging condition.

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

Research has shown that NALIRIFOX, a combination of four drugs, holds promise for treating pancreatic cancer. This treatment can shrink tumors in patients with advanced pancreatic cancer, increasing the likelihood of surgery. Liposomal irinotecan, one of the drugs, targets cancer cells while minimizing side effects. Earlier studies found that patients using this combination lived longer on average and experienced better outcomes compared to other treatments. These findings suggest that NALIRIFOX could enhance the chances of successful surgery and reduce the risk of cancer recurrence in pancreatic cancer patients. ^{1 2 3 6 7}

Who Is on the Research Team?

Christos Fountzilas

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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 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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e16447

A phase II study of NALIRIFOX (liposomal irinotecan, 5- ... This study evaluates the efficacy and safety of NALIRIFOX regimen in LAPC pts, aiming to facilitate conversion to surgical resection and improve survival ...

2. 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).

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) ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S294981982500086X

Long-term survival in patients with pancreatic cancer ... The 2L recommendation for the treatment of mPAC stems from the pivotal global phase 3 NAPOLI-1 trial which reported a 1-year overall survival (OS) rate of 26% [ ...

5. targetedonc.com targetedonc.com/view/nalirifox-dose-reductions-maintain-efficacy-in-pancreatic-cancer

NALIRIFOX Dose Reductions Maintain Efficacy in ... [With NALIRIFOX], patients who had dose reduction did better. Patients who had dose reductions when the liposomal irinotecan was dose reduced; ...

6. asco.org asco.org/abstracts-presentations/ABSTRACT320565

Efficacy and safety of liposomal irinotecan plus fluorouracil ... Objective response rate of nal-IRI + 5-FU/LV was 2.9% (1 partial response) and stable disease was achieved in 31.4% (n = 11). With median follow-up duration of ...

7. 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).