Combination Chemotherapy for Pancreatic Cancer

Recruiting at 8 trial locations

Overseen By Christina Wiess, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

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: Unknown

46 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well combination chemotherapy before and after surgery works in treating patients with localized pancreatic cancer. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does mention that no other concurrent anticancer therapy is allowed, so you may need to discuss your current medications with the trial team.

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

Research indicates that the FOLFIRINOX combination, which includes fluorouracil, leucovorin, irinotecan, and oxaliplatin, has shown superiority as a first-line therapy for metastatic pancreatic cancer compared to other standard treatments like gemcitabine. ^{1 2 3 4 5}

Is the combination chemotherapy for pancreatic cancer generally safe for humans?

The combination chemotherapy involving 5-fluorouracil (5-FU), irinotecan, and oxaliplatin, known as FOLFIRINOX, has been used for advanced pancreatic cancer but is associated with significant side effects like fatigue, neuropathy (nerve damage), and nausea. Modified versions of these regimens, such as mFOLFIRINOX and mFOLFIRI, have been found to be tolerable, though they still carry risks of adverse events. ^{3 6 7 8 9}

What makes the FOLFIRINOX drug unique for treating pancreatic cancer?

FOLFIRINOX is unique because it combines four drugs (fluorouracil, leucovorin, irinotecan, and oxaliplatin) that work together to improve survival in patients with metastatic pancreatic cancer, especially those with good overall health, compared to the standard treatment with gemcitabine. ^{3 10 11 12 13}

Research Team

Jill Lacy, MD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for patients with localized pancreatic cancer who haven't had previous treatments. They should be able to undergo surgery, have no other cancers or major health issues like heart disease, uncontrolled seizures, serious lung fibrosis, or severe nerve damage in the hands and feet. Participants need good organ function and an ECOG performance status of 0-1 (fully active or restricted in physically strenuous activity but ambulatory).

Inclusion Criteria

Your blood tests for counts, hemoglobin, creatinine, bilirubin, AST, and ALT need to be within a certain range, and women of childbearing age must have a negative pregnancy test.

My pancreatic cancer can be surgically removed and hasn't spread outside the pancreas.

I do not have serious heart problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Therapy

Patients receive mFOLFIRINOX chemotherapy every 2 weeks for 6 courses

12 weeks

Surgery

Patients undergo surgical resection 3-8 weeks after completion of neoadjuvant therapy

3-8 weeks

Adjuvant Therapy

Patients receive mFOLFIRINOX chemotherapy every 2 weeks for up to 6 courses after surgery

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Fluorouracil
• Irinotecan Hydrochloride
• Leucovorin Calcium
• Oxaliplatin
• Therapeutic Conventional Surgery

Trial Overview The study tests a combination of chemotherapy drugs (leucovorin calcium, fluorouracil, irinotecan hydrochloride, oxaliplatin) given before and after surgery to see if they can shrink pancreatic tumors pre-surgery and eliminate remaining cancer cells post-surgery.

Participant Groups

Group I: Treatment (mFOLFIRINOX) Experimental Treatment 6 Interventions

NEOADJUVANT THERAPY: Patients receive mFOLFIRINOX comprising oxaliplatin IV over 2 hours, levoleucovorin calcium IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and fluorouracil IV continuously for 46 hours on day 1. Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. SURGERY: Beginning 3-8 weeks after completion of neoadjuvant therapy patients undergo surgical resection. ADJUVANT THERARPY: Beginning within 12 weeks after surgery, patients receive mFOLFIRINOX as in neoadjuvant therapy. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Fluorouracil is already approved in United States, European Union, Canada for the following indications:

Approved in United States as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Skin cancer

Approved in European Union as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Approved in Canada as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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 485 patients with localized pancreatic cancer, those treated with FOLFIRINOX showed higher rates of partial response according to RECIST criteria compared to those treated with gemcitabine plus nab-paclitaxel (GA), indicating better initial tumor response.

Despite the higher response rates and more frequent surgeries (pancreatectomy) in the FOLFIRINOX group, overall survival rates were similar between the two treatment regimens, suggesting that while FOLFIRINOX may be more effective in shrinking tumors, it does not necessarily lead to longer survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response and Survival Associated With First-line FOLFIRINOX vs Gemcitabine and nab-Paclitaxel Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma. Perri, G., Prakash, L., Qiao, W., et al.[2022]

FOLFIRINOX treatment in metastatic pancreatic carcinoma showed a median overall survival of 10 months, with similar efficacy whether used in first- or second-line therapy, indicating its effectiveness as a treatment option.

Patients with tumors located in the head of the pancreas had a poorer prognosis, with a median survival of only 8 months, compared to 14 months for those with tumors in the body or tail, highlighting the importance of tumor location in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influcence of localization of primary tumor on effectiveness of 5-fluorouracil/leucovorin combined with irinotecan and oxaliplatin (FOLFIRINOX) in patients with metastatic pancreatic adenocarcinoma: a retrospective study. Lorgis, V., Chauffert, B., Gentil, 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 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]

In a study of 825 patients with metastatic pancreatic ductal adenocarcinoma receiving second-line chemotherapy, those treated with liposomal irinotecan-based regimens experienced the lowest rates of severe blood-related adverse events like anemia, neutropenia, and thrombocytopenia compared to other regimens such as FOLFIRINOX and FOLFOX.

Patients on liposomal irinotecan also required similar or fewer medications to manage these adverse events, indicating a potentially safer and more manageable treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world safety and supportive care use of second-line 5-fluorouracil-based regimens among patients with metastatic pancreatic ductal adenocarcinoma. Kim, G., Cockrum, P., Surinach, A., et al.[2023]

In a phase II study involving 23 patients with metastatic pancreatic carcinoma, the combination of 5-fluorouracil, leucovorin, and interferon alpha-2a showed no objective clinical responses, with 14 out of 18 evaluable patients experiencing disease progression.

The treatment was associated with significant toxicity, primarily nausea and vomiting, leading to notable hospitalization rates, indicating that this regimen is ineffective and poses considerable risks even for patients with good performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of 5-fluorouracil, leucovorin, and interferon alpha 2A (IFN-alpha 2a) in metastatic pancreatic carcinoma: a Penn Cancer Clinical Trials Group (PCCTG) trial. David, AK., Vaughn, DJ., Holroyde, CP., et al.[2019]

In a phase II study involving 20 patients with advanced pancreatic cancer, the combination of gemcitabine and 5-fluorouracil (5-FU) demonstrated modest antitumor activity, with a 25% overall response rate and a clinical benefit response in 41.7% of assessable patients.

The treatment was generally well tolerated, with manageable side effects, including neutropenia and thrombocytopenia occurring in 9.3% and 5.3% of patients, respectively, and a median survival of 8.0 months for participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and Infusional 5-Fluorouracil in Advanced Pancreatic Cancer: A Clinical Benefit Response-Oriented Phase II Study. Choi, JH., Ahn, MJ., Im, SA., et al.[2015]

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]

In a phase II trial involving 21 patients with untreated advanced pancreatic cancer, the combination treatment of trimetrexate, leucovorin, and 5-fluorouracil (NFL) was found to be well-tolerated, with serious toxicities occurring in a minority of patients (23.8% experienced Grade 3 diarrhea).

The treatment resulted in a median survival of 6.8 months and a 1-year survival rate of 19%, which is comparable to other available treatment options for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II clinical trial of 5-fluorouracil, trimetrexate, and leucovorin (NFL) in patients with advanced pancreatic cancer. Garcia, AA., Leichman, L., Baranda, J., et al.[2018]

In a study of 493 patients with resected pancreatic cancer, the modified FOLFIRINOX regimen resulted in significantly longer disease-free survival (21.6 months) and overall survival (54.4 months) compared to gemcitabine (12.8 months and 35.0 months, respectively).

While modified FOLFIRINOX showed better efficacy, it also had a higher incidence of severe adverse events (75.9% vs. 52.9% for gemcitabine), indicating a trade-off between effectiveness and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. Conroy, T., Hammel, P., Hebbar, M., et al.[2023]

References

1. Turkey pubmed.ncbi.nlm.nih.gov

Folfirinox versus gemcitabine-cisplatin combination as first-line therapy in treatment of pancreaticobiliary cancer [2023]

2. 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]

3. 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]

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

Response and Survival Associated With First-line FOLFIRINOX vs Gemcitabine and nab-Paclitaxel Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma. [2022]

5. Greece pubmed.ncbi.nlm.nih.gov

Influcence of localization of primary tumor on effectiveness of 5-fluorouracil/leucovorin combined with irinotecan and oxaliplatin (FOLFIRINOX) in patients with metastatic pancreatic adenocarcinoma: a retrospective study. [2022]

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. England pubmed.ncbi.nlm.nih.gov

Real-world safety and supportive care use of second-line 5-fluorouracil-based regimens among patients with metastatic pancreatic ductal adenocarcinoma. [2023]

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

A phase II trial of 5-fluorouracil, leucovorin, and interferon alpha 2A (IFN-alpha 2a) in metastatic pancreatic carcinoma: a Penn Cancer Clinical Trials Group (PCCTG) trial. [2019]

10. Korea (South) pubmed.ncbi.nlm.nih.gov

Gemcitabine and Infusional 5-Fluorouracil in Advanced Pancreatic Cancer: A Clinical Benefit Response-Oriented Phase II Study. [2015]

11. England pubmed.ncbi.nlm.nih.gov

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

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

Phase II clinical trial of 5-fluorouracil, trimetrexate, and leucovorin (NFL) in patients with advanced pancreatic cancer. [2018]

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

FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. [2023]