Neoadjuvant Therapy for Pancreatic Cancer

Recruiting at 1 trial location

Overseen By Davendra Sohal, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Cincinnati

Must not be taking: Investigational agents

Disqualifiers: Uncontrolled illness, Pregnant, Breastfeeding, others

Stay on Your Current Meds You can continue your current medications while participating

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

32 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

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

What data supports the effectiveness of this treatment for pancreatic cancer?

Research shows that FOLFIRINOX, a combination of drugs, is more effective than gemcitabine for patients with metastatic pancreatic cancer, leading to better survival rates. Additionally, when used as a neoadjuvant therapy (treatment given before the main treatment), FOLFIRINOX has shown promising results in improving outcomes for patients with locally advanced pancreatic cancer. ^{1 2 3 4 5}

Is neoadjuvant therapy for pancreatic cancer generally safe for humans?

FOLFIRINOX and gemcitabine-based treatments for pancreatic cancer have different safety profiles. FOLFIRINOX may cause more vomiting and diarrhea, while gemcitabine can lead to more anemia. Both treatments are used in advanced pancreatic cancer, but their side effects vary. ^{6 7 8 9 10}

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

FOLFIRINOX is a combination of four drugs (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) that has shown higher response rates in treating metastatic pancreatic cancer compared to gemcitabine-based treatments. It is being explored as a neoadjuvant therapy (treatment given before the main treatment) for locally advanced pancreatic cancer, which is a newer approach compared to its use in metastatic cases. ^{1 4 11 12 13}

What is the purpose of this trial?

The purpose of this study is to determine if neoadjuvant therapy to increases resection rate for pancreatic adenocarcinoma.

Research Team

Davendra P. Sohal

Principal Investigator

University of Cincinnati

Eligibility Criteria

This trial is for adults with confirmed pancreatic carcinoma or adenocarcinoma who haven't had prior treatment for it. They must be in good health otherwise, not have other serious illnesses that could affect the study, and agree to use contraception. People with controlled HIV or cured hepatitis are eligible, but pregnant women and those unable to follow the study plan can't join.

Inclusion Criteria

I had hepatitis C but am cured, or I'm being treated with no detectable virus.

I had cancer before, but it was treated over 2 years ago and won't affect this study.

I am fully active and can carry on all my pre-disease activities without restriction.

Exclusion Criteria

You are not currently taking any other experimental medications. If you have taken experimental medications in the past but are not currently taking them, the decision to include you will be made by the Principal Investigator.

Pregnant women or women who are breastfeeding are excluded from this study.

I do not have any health conditions that would stop me from receiving standard cancer treatments.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive FOLFIRINOX regimen, with potential switch to gemcitabine and nab-paclitaxel based on interim assessment

16 months

Regular visits for chemotherapy administration and assessment

Radiation Therapy

Radiation therapy may be used prior to surgery based on pre-operative scan findings

As needed prior to surgery

Surgical Resection

Participants undergo surgical resection if deemed resectable after neoadjuvant therapy

Surgery scheduled post-therapy

Follow-up

Participants are monitored for safety, effectiveness, and survival after treatment

5 years

Regular follow-up visits for monitoring

Treatment Details

Interventions

• Folfirinox
• Gemcitabine
• Pancreatectomy
• Radiation Therapy

Trial Overview The trial tests if neoadjuvant therapy (treatment given before main treatment) increases the chance of successfully removing pancreatic tumors through surgery. It involves a combination of chemotherapy drugs like Gemcitabine and Folfirinox, along with radiation therapy before a pancreatectomy.

Participant Groups

Group I: Neoadjuvant therapy Experimental Treatment 4 Interventions

All patients will receive Neoadjuvant therapy.

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

Approved in United States as FOLFIRINOX for:

• Pancreatic cancer

Approved in European Union as FOLFIRINOX for:

• Pancreatic cancer

Who Is Running the Clinical Trial?

University of Cincinnati

Lead Sponsor

Trials

442

Recruited

639,000+

Findings from Research

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 274 pancreatic ductal adenocarcinoma (PDAC) patients, those who showed a significant biochemical response (CA 19-9 decrease ≥50%) after neoadjuvant chemotherapy had better overall survival (OS) and recurrence-free survival compared to those with less response, indicating the importance of monitoring this biomarker.

The study found no significant difference in survival outcomes between patients treated with the two chemotherapy regimens, FOLFIRINOX (FLX) and gemcitabine/nab-paclitaxel (GNP), suggesting that both are equally effective in improving survival rates in PDAC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival Outcomes Associated With Clinical and Pathological Response Following Neoadjuvant FOLFIRINOX or Gemcitabine/Nab-Paclitaxel Chemotherapy in Resected Pancreatic Cancer. Macedo, FI., Ryon, E., Maithel, SK., et al.[2022]

In a study of 83 patients with metastatic pancreatic ductal adenocarcinoma, the FOLFIRINOX (FFX) regimen showed the best progression-free survival (PFS) of 9 months compared to 5 months for both gemcitabine-based regimens (GB) and gemcitabine monotherapy (Gem).

Overall survival (OS) was also highest for the FFX group at 14 months, indicating that FFX may be the most effective first-line treatment option for this condition, with male gender, ECOG performance status, and elevated neutrophil-to-lymphocyte ratio identified as independent predictors of survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Life Results of Palliative Chemotherapy in Metastatic Pancreatic Ductal Adenocarcinoma. Varzaru, B., Iacob, RA., Croitoru, AE., et al.[2023]

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 study of 92 patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (PDAC) treated with FOLFIRINOX and radiation, 16% achieved a complete pathological response, indicating the treatment's effectiveness in the neoadjuvant setting.

The study identified a tumour-to-tumour bed ratio of 11.6% as a significant predictor of overall survival, suggesting that this quantitative measure may be more reliable than traditional pathology parameters for assessing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreatic ductal adenocarcinoma: tumour regression grading following neoadjuvant FOLFIRINOX and radiation. Neyaz, A., Tabb, ES., Shih, A., et al.[2023]

In a phase II trial involving 48 patients with gemcitabine-refractory unresectable pancreatic cancer, modified FOLFIRINOX demonstrated promising efficacy with an objective response rate of 18.8% and a disease control rate of 62.5%.

The treatment was associated with manageable safety concerns, primarily neutropenia (64.6% of patients), but most non-hematologic adverse events were mild, indicating that while effective, careful monitoring for hematologic toxicities is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase II trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer. Chung, MJ., Kang, H., Kim, HG., et al.[2020]

In a meta-analysis of 16 studies involving 3813 patients with metastatic pancreatic cancer, both GEM-NAB and FOLFIRINOX showed similar overall survival rates, despite FOLFIRINOX having a numerically longer median overall survival.

GEM-NAB was associated with lower rates of nausea and severe neutropenia compared to FOLFIRINOX, while FOLFIRINOX had lower rates of neurotoxicity and anemia, indicating that the choice between these treatments may depend on the patient's tolerance to side effects rather than a clear efficacy advantage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Gemcitabine plus Nab-Paclitaxel and FOLFIRINOX in the First-Line Setting of Metastatic Pancreatic Cancer: A Systematic Review and Meta-Analysis. Pusceddu, S., Ghidini, M., Torchio, M., et al.[2020]

In a study of 18 patients with metastatic pancreatic cancer, the maximum tolerated dose (MTD) for second-line chemotherapy using FOLFIRINOX was determined to be 100 mg/m² of irinotecan, with a response rate of 22.2% and a disease control rate of 61.1%.

The most common severe side effect was neutropenia, affecting 66.7% of patients, indicating that while FOLFIRINOX can be marginally effective after gemcitabine failure, it carries significant risks of toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of FOLFIRINOX as second-line chemotherapy for metastatic pancreatic cancer after gemcitabine-based chemotherapy failure. Kobayashi, N., Shimamura, T., Tokuhisa, M., et al.[2022]

In a comparison of two chemotherapy regimens for metastatic pancreatic cancer, FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GN), both treatments showed equivalent overall survival of 11.1 months and similar progression-free survival rates, indicating comparable efficacy.

However, the safety profiles differed: GN was associated with more frequent grade 3/4 anemia, while FFX led to higher rates of grade 3/4 vomiting and diarrhea, suggesting that while both treatments are effective, their side effects vary significantly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Equivalent Efficacy but Different Safety Profiles of Gemcitabine Plus Nab-Paclitaxel and FOLFIRINOX in Metastatic Pancreatic Cancer. Rapposelli, IG., Casadei-Gardini, A., Vivaldi, C., et al.[2022]

In a study involving 342 patients with metastatic pancreatic adenocarcinoma, FOLFIRINOX demonstrated a significantly better overall survival compared to gemcitabine, with a net chance of a better outcome of 24.7 (P<.001).

The analysis indicated that FOLFIRINOX has a favorable benefit-risk balance, meaning that the survival benefits outweigh the associated toxicities when compared to gemcitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An assessment of the benefit-risk balance of FOLFIRINOX in metastatic pancreatic adenocarcinoma. Péron, J., Roy, P., Conroy, T., 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]

Patients with metastatic pancreatic cancer treated with Folfirinox (FFX) had a significantly longer overall survival (14 months) compared to those treated with gemcitabine/nab-paclitaxel (GN) (9 months), indicating that FFX may be a more effective first-line treatment.

The study suggests that using FFX followed by GN after FFX failure is more feasible, with a higher proportion of patients able to receive GN after FFX treatment, leading to a median overall survival of 19 months compared to 9.5 months for the reverse sequence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Folfirinox versus gemcitabine/nab-paclitaxel as first-line therapy in patients with metastatic pancreatic cancer: a comparative propensity score study. Williet, N., Saint, A., Pointet, AL., et al.[2022]

In a study of 342 patients with metastatic pancreatic cancer, the FOLFIRINOX chemotherapy regimen significantly improved overall survival (11.1 months) compared to gemcitabine (6.8 months), indicating it is a more effective first-line treatment option.

While FOLFIRINOX showed a higher objective response rate (31.6% vs. 9.4% for gemcitabine), it also resulted in more adverse events, including a 5.4% incidence of febrile neutropenia, highlighting the need to balance efficacy with safety in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. Conroy, T., Desseigne, F., Ychou, M., et al.[2023]

References

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

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

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

Survival Outcomes Associated With Clinical and Pathological Response Following Neoadjuvant FOLFIRINOX or Gemcitabine/Nab-Paclitaxel Chemotherapy in Resected Pancreatic Cancer. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Real-Life Results of Palliative Chemotherapy in Metastatic Pancreatic Ductal Adenocarcinoma. [2023]

4. England pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

Pancreatic ductal adenocarcinoma: tumour regression grading following neoadjuvant FOLFIRINOX and radiation. [2023]

6. China pubmed.ncbi.nlm.nih.gov

Multicenter phase II trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer. [2020]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Gemcitabine plus Nab-Paclitaxel and FOLFIRINOX in the First-Line Setting of Metastatic Pancreatic Cancer: A Systematic Review and Meta-Analysis. [2020]

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

Effect of FOLFIRINOX as second-line chemotherapy for metastatic pancreatic cancer after gemcitabine-based chemotherapy failure. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Equivalent Efficacy but Different Safety Profiles of Gemcitabine Plus Nab-Paclitaxel and FOLFIRINOX in Metastatic Pancreatic Cancer. [2022]

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

An assessment of the benefit-risk balance of FOLFIRINOX in metastatic pancreatic adenocarcinoma. [2022]

11. Greece pubmed.ncbi.nlm.nih.gov

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

12. England pubmed.ncbi.nlm.nih.gov

Folfirinox versus gemcitabine/nab-paclitaxel as first-line therapy in patients with metastatic pancreatic cancer: a comparative propensity score study. [2022]

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

FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. [2023]