FOLFIRINOX for Pancreatic Cancer

Overseen By Brian Burgess, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must not be taking: Ketoconazole, St John's wort

Disqualifiers: Metastatic cancer, Heart disease, 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: 8

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine how the genetic makeup of pancreatic cancer affects its response to the chemotherapy treatment FOLFIRINOX, administered before surgery to remove the tumor. The treatment combines several chemotherapy drugs, including 5-FU (Fluorouracil), Irinotecan Hydrochloride, Leucovorin, and Oxaliplatin, with one requiring a home infusion over two days. Researchers hope the treatment can shrink tumors, making them easier to remove and preventing recurrence. This study suits those with pancreatic cancer that hasn't spread and isn't yet surgically removable. Participants must also agree to have biopsies (tissue samples) taken before and after chemotherapy.

As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must stop using ketoconazole or St John's wort. Use of phenytoin, carbamazepine, phenobarbital, rifampin, and rifabutin is discouraged, but not completely prohibited.

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

Studies have shown that FOLFIRINOX, a chemotherapy treatment for pancreatic cancer, is generally well-tolerated by patients. This treatment combines four drugs: oxaliplatin, leucovorin, irinotecan, and 5-fluorouracil (5-FU). Research indicates that while FOLFIRINOX can cause side effects, most patients manage them well with proper medical care. Common side effects include fatigue, nausea, and lower blood counts, which can lead to infections. However, the benefits of FOLFIRINOX often outweigh these risks, as it can extend patient survival and reduce the chance of cancer recurrence. Patients should always discuss potential side effects and management strategies with their medical team. ^{1 2 3 4 5}

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

Researchers are excited about FOLFIRINOX because it combines four powerful drugs—5-FU, Irinotecan, Leucovorin, and Oxaliplatin—to tackle pancreatic cancer more aggressively. Unlike standard treatments like gemcitabine, which often work alone, this combination attacks cancer cells on multiple fronts, potentially leading to better outcomes. Moreover, FOLFIRINOX allows for the possibility of surgical resection after eight cycles if the cancer becomes resectable, offering a chance for more comprehensive treatment.

What is the effectiveness track record for FOLFIRINOX in treating pancreatic cancer?

Research has shown that FOLFIRINOX can effectively treat pancreatic cancer. Studies have found that patients with locally advanced pancreatic cancer who received FOLFIRINOX lived an average of 24.2 months, longer than usual for similar cases. This treatment combines four drugs, including 5-FU, which helps prevent cancer from returning after surgery. Although FOLFIRINOX can cause side effects, its potential to extend patients' lives offers hope for those with pancreatic cancer. Early research is exploring whether administering FOLFIRINOX before surgery can make tumors easier to remove and prevent recurrence. ^{2 6 7 8 9}

Who Is on the Research Team?

Ashwin Somasundaram, MD

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a specific type of pancreatic cancer (adenocarcinoma) that hasn't spread or been treated yet. They must be able to have biopsies, potentially undergo surgery, and have no major health issues that would prevent surgery. Participants need good organ function and an expected lifespan of at least 6 months. Women who can bear children must test negative for pregnancy and use birth control.

Inclusion Criteria

I am considered fit for surgery to remove pancreatic cancer by a surgeon.

I have not had chemotherapy, chemoradiotherapy, or surgery for pancreatic cancer.

Subject has life expectancy of at least 6 months

Exclusion Criteria

Subject has current evidence of any condition that makes participating in this study not in the best interest of the subject

I am allergic to certain chemotherapy drugs like 5FU, oxaliplatin, or irinotecan.

I have not had major surgery or a significant injury in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive FOLFIRINOX chemotherapy every 14 days for up to 12 cycles (24 weeks) or until disease progression, unacceptable toxicity, study withdrawal, or subject death.

24 weeks

Bi-weekly visits for chemotherapy administration

Surgical Assessment

Participants are reassessed for resectability after 8 cycles of chemotherapy. Surgery may be pursued if the disease is deemed resectable.

8 weeks

Imaging and surgical consultation after 8 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up continuing for 36 months or until death.

36 months

What Are the Treatments Tested in This Trial?

Interventions

• 5-FU
• Irinotecan Hydrochloride
• Leucovorin
• Oxaliplatin

Trial Overview The study tests if the FOLFIRINOX chemotherapy regimen—combining oxaliplatin, leucovorin, irinotecan hydrochloride, and 5-FU—can make pancreatic tumors easier to remove surgically by changing their genetic profile. It involves pre- and post-treatment biopsies to see how the tumor's DNA changes after eight treatments.

How Is the Trial Designed?

Group I: SingleArm: FOLFIRINOX Experimental Treatment 4 Interventions

Subjects will receive FOLFIRINOX as an outpatient every 14 days per community standards of medical care. Protocol-based therapy will continue for 12 cycles (24 weeks) or until disease progression, unacceptable toxicity, study withdrawal, or subject death. Subjects will have the option of surgical resection after 8 cycles of therapy if repeat scans show evidence of resectable disease. The starting doses for mFOLFIRINOX regimen are: oxaliplatin 85 mg/m2, followed by leucovorin 400 mg/m2 given simultaneously with irinotecan 180mg/m2, followed by 5FU 400 mg/m2 bolus and then 2400 mg/m2 via continuous infusion.

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?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

Published Research Related to This Trial

In a study of 19 patient-derived pancreatic cancer cell lines, FOLFIRINOX showed optimal sensitivity in six cell lines, while three cell lines responded better to gemcitabine plus nab-paclitaxel (Gem-Pac), indicating that different regimens may work better for different patients.

The findings suggest that understanding the specific sensitivity of cancer cells to these treatments could help identify biomarkers, which may guide personalized chemotherapy choices for patients with pancreatic ductal adenocarcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX Versus Gemcitabine-based Therapy for Pancreatic Ductal Adenocarcinoma: Lessons from Patient-derived Cell Lines. Begg, SKS., Birnbaum, DJ., Clark, JW., et al.[2023]

The introduction of FOLFIRINOX and gemcitabine plus nab-paclitaxel therapy significantly improved treatment outcomes for metastatic pancreatic cancer, with response rates increasing from 7.8% to 28.4% after these therapies were introduced.

Patients treated with the newer therapies experienced longer median progression-free survival (3.1 months to 5.4 months) and median overall survival (6.7 months to 10.2 months), indicating a substantial benefit in daily clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement of Treatment Outcomes for Metastatic Pancreatic Cancer: A Real-world Data Analysis. Sasaki, T., Kanata, R., Yamada, I., et al.[2022]

A nomogram was developed to predict 6-month survival in patients with metastatic and locally advanced pancreatic cancer treated with FOLFIRINOX, based on four key prognostic factors: performance status, liver metastases, baseline carbohydrate antigen 19-9 level, and neutrophil-to-lymphocyte ratio.

The nomogram demonstrated good accuracy in predicting outcomes, with a C index of 0.762 in an independent validation cohort, helping to identify patient subsets with varying prognoses based on the number of poor prognostic features.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validated Nomogram Predicting 6-Month Survival in Pancreatic Cancer Patients Receiving First-Line 5-Fluorouracil, Oxaliplatin, and Irinotecan. Fornaro, L., Leone, F., Vienot, A., et al.[2020]

In a study of 1835 patients with localized pancreatic ductal adenocarcinoma (PDAC) treated with (m)FOLFIRINOX, the median overall survival was 18.7 months for locally advanced cases, 23.2 months for borderline resectable cases, and 31.2 months for potentially resectable cases, indicating varying outcomes based on disease stage.

The study also found that 37.9% of patients underwent surgical resection, with a median overall survival of 38.3 months for those who had surgery, highlighting the importance of resectability in improving survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX as Initial Treatment for Localized Pancreatic Adenocarcinoma: A Retrospective Analysis by the Trans-Atlantic Pancreatic Surgery Consortium. Janssen, QP., van Dam, JL., Doppenberg, D., et al.[2023]

In a study of 1102 patients with metastatic pancreatic cancer, FOLFIRINOX treatment resulted in a median overall survival of 9.27 months, significantly longer than the 6.87 months observed with gemcitabine plus nab-paclitaxel (P < 0.001).

Patients receiving FOLFIRINOX also experienced 17.3% fewer posttreatment hospitalizations and 20% lower posttreatment costs compared to those treated with gemcitabine plus nab-paclitaxel, indicating better safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of FOLFIRINOX vs Gemcitabine Plus Nab-Paclitaxel as First-Line Chemotherapy for Metastatic Pancreatic Ductal Adenocarcinoma. Klein-Brill, A., Amar-Farkash, S., Lawrence, G., et al.[2023]

In a study of 40 patients with advanced pancreatic cancer who had previously failed gemcitabine therapy, the mFOLFIRI regimen demonstrated a median progression-free survival of 2.59 months and overall survival of 4.75 months, indicating it may be a tolerable and relatively effective treatment option.

The most common side effects included fatigue (98%), neuropathy (83%), and anorexia (68%), with manageable grade 3 toxicities, suggesting that while mFOLFIRI has some adverse effects, it does not lead to severe complications (grade 4 toxicities were not observed).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified irinotecan and infusional 5-fluorouracil (mFOLFIRI) in patients with refractory advanced pancreas cancer (APC): a single-institution experience. Bupathi, M., Ahn, DH., Wu, C., et al.[2018]

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 FOLFIRINOX regimen, which includes multiple chemotherapy agents, has been used in clinical practice for patients with metastatic and locally advanced pancreatic cancer, showing potential safety and efficacy, especially in those with good performance status.

There is a need for further research, including a phase III randomized study, to better understand the role of FOLFIRINOX in treating locally advanced pancreatic cancer, particularly given the modifications made to the regimen in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of the FOLFIRINOX regimen for advanced pancreatic cancer. Conroy, T., Gavoille, C., Samalin, E., et al.[2021]

In a study of 289 patients with advanced pancreatic ductal adenocarcinoma, the FOLFOXIRI chemotherapy regimen showed similar overall survival (11.1 months) compared to the standard FOLFIRINOX regimen (11.6 months), indicating no significant therapeutic advantage for FOLFOXIRI.

FOLFOXIRI was associated with a higher incidence of grade 3/4 digestive adverse events (28.7% vs. 19.5% for FOLFIRINOX), suggesting that while it is feasible, it may lead to more severe side effects without improving survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: A population-based cohort study. Vienot, A., Chevalier, H., Bolognini, C., et al.[2020]

In a study of 18 patients with locally advanced pancreatic cancer (LAPC), neoadjuvant therapy using FOLFIRINOX resulted in a promising R0 resection rate of 44%, indicating that a significant portion of patients became eligible for surgical removal of their tumors after treatment.

The treatment showed high efficacy with a 1-year overall survival rate of 100% and a progression-free survival rate of 83%, although it was associated with notable chemotherapy-related toxicities, including neutropenia and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. Hosein, PJ., Macintyre, J., Kawamura, C., 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38319559/

Real Life Data and Outcome of FOLFIRINOX Use in ... Survival rates for patient with metastatic pancreatic cancer treated with FOLFIRINOX were worse in our study population than in comparative studies.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1011923

FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic ... Data are lacking on the efficacy and safety of a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin ...

3. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-020-07110-x

Meta-analysis examining overall survival in patients with ... Pancreatic cancer has a poor prognosis and few choices of therapy. For patients with adequate performance status, FOLFIRINOX or gemcitabine ...

4. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(16)00172-8/abstract

FOLFIRINOX for locally advanced pancreatic cancer Patients with locally advanced pancreatic cancer treated with FOLFIRINOX had a median overall survival of 24·2 months—longer than that reported ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)33892-X/fulltext

Effectiveness and costs of FOLFIRINOX in the treatment ... In terms of safety profile, it was documented a high incidence of adverse effects grade 3 or 4, mainly hematologic with 7.5% of patients experiencing febrile ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8171163/

Efficacy and safety of modified fluorouracil/leucovorin plus ... We retrospectively reviewed 76 consecutive patients with metastatic pancreatic adenocarcinoma who underwent mFOLFIRINOX or S‐1 treatment as a ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11871866/

Outcomes of Liposomal Irinotecan With 5‐FU and ... This study investigated the effectiveness and safety of liposomal irinotecan plus 5-fluorouracil (5-FU) and leucovorin (LV) as a second-line ...

8. wjso.biomedcentral.com wjso.biomedcentral.com/articles/10.1186/s12957-021-02291-6

The role of FOLFIRINOX in metastatic pancreatic cancer Here, we report the efficacy and safety of FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, 5-fluorouracil) in the treatment of metastatic PC.

9. sciencedirect.com sciencedirect.com/science/article/pii/S1424390322001946

Nal-IRI/5-FU/LV versus modified FOLFIRINOX and FOLFIRI ... The primary endpoint was the overall survival (OS) of all patients, excluding those with locally advanced pancreatic cancer. Regarding safety, we assessed the ...