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

Trial Summary

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.

What data supports the effectiveness of the drug FOLFIRINOX for treating pancreatic cancer?

Research shows that FOLFIRINOX, a combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin, is more effective than gemcitabine for patients with metastatic pancreatic cancer who are in good health. It is also used as a first-line treatment for both metastatic and locally advanced pancreatic cancer, although specific criteria for predicting better outcomes are not well established. ^{1 2 3 4 5}

Is FOLFIRINOX safe for treating pancreatic cancer?

FOLFIRINOX, a combination of several drugs, is used for treating pancreatic cancer but is known to have significant side effects. Common side effects include fatigue, neuropathy (nerve damage), anorexia (loss of appetite), nausea, and constipation. Modifications to the regimen, like removing certain components, have been made to improve safety while maintaining effectiveness. ^{4 6 7 8 9}

What makes the FOLFIRINOX treatment unique for pancreatic cancer?

FOLFIRINOX is unique because it combines four drugs (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) and is often used for patients with advanced pancreatic cancer who are in good health. It is considered more effective than gemcitabine for those who can tolerate its side effects, offering a more aggressive treatment option. ^{1 2 4 10 11}

What is the purpose of this trial?

This is a research study to evaluate how the genetic makeup of Pancreatic Ductal Adenocarcinoma (PDAC) can affect the response to FDA-approved chemotherapy treatment, FOLFIRINOX, given before surgery to remove the tumor. Certain types of PDAC tumors can be surgically resected (removed). However, not all types of PDACs are resectable, especially if they are close to important structures like blood vessels or intestines. These types of PDACs are treated with chemotherapy such as FOLFIRINOX. Research studies showed that chemotherapy after surgical resection of PDAC tumors reduced the risk of the cancer returning. Chemotherapy is used to treat PDAC that has not spread outside of the pancreas and is not resectable. FOLFIRINOX is a chemotherapy treatment that combines multiple chemotherapeutic agents, including oxaliplatin, leucovorin, irinotecan, and 5-FU. Patients receive these agents by intravenous infusion. Of these drugs, 5-FU requires you to return home with a chemotherapy pump that will deliver chemotherapy over 46 hours. This regimen has been studied in pancreatic cancer that has been removed with surgery as a method for preventing the cancer from returning. Studies showed FOLFIRINOX chemotherapy reduced the risk of cancer returning and increased patients survival. In this study, researchers want to know if FOLFIRINOX chemotherapy given before surgery will make the cancer easier to remove with surgery and increase the chances of the cancer staying away after surgery. Researchers have shown that pancreatic cancers are not all the same when you look at the DNA and RNA that is inside a pancreatic cancer cell. Depending on the expression of different genes in a cancer cell, some pancreatic cancers may respond differently to chemotherapy. In this study researchers want to know if FOLFIRINOX chemotherapy can change the genetic profile of the cancer. This will be studied by obtaining a biopsy of the cancer before the start of chemotherapy, and after 8 treatments of chemotherapy. They will also study cancer cells that will be collected from blood samples.

Research Team

Ashwin Somasundaram, MD

Principal Investigator

University of North Carolina, Chapel Hill

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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 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 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 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]

References

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

A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. [2022]

2. Greece pubmed.ncbi.nlm.nih.gov

Improvement of Treatment Outcomes for Metastatic Pancreatic Cancer: A Real-world Data Analysis. [2022]

3. Greece pubmed.ncbi.nlm.nih.gov

FOLFIRINOX Versus Gemcitabine-based Therapy for Pancreatic Ductal Adenocarcinoma: Lessons from Patient-derived Cell Lines. [2023]

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

Validated Nomogram Predicting 6-Month Survival in Pancreatic Cancer Patients Receiving First-Line 5-Fluorouracil, Oxaliplatin, and Irinotecan. [2020]

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

FOLFIRINOX as Initial Treatment for Localized Pancreatic Adenocarcinoma: A Retrospective Analysis by the Trans-Atlantic Pancreatic Surgery Consortium. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Modified irinotecan and infusional 5-fluorouracil (mFOLFIRI) in patients with refractory advanced pancreas cancer (APC): a single-institution experience. [2018]

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

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

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

The role of the FOLFIRINOX regimen for advanced pancreatic cancer. [2021]

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

Comparison of FOLFIRINOX vs Gemcitabine Plus Nab-Paclitaxel as First-Line Chemotherapy for Metastatic Pancreatic Ductal Adenocarcinoma. [2023]

11. China pubmed.ncbi.nlm.nih.gov

FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: A population-based cohort study. [2020]