Chemotherapy for Pancreatic Cancer

Overseen By Ryan Romasko

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fox Chase Cancer Center

Disqualifiers: Brain metastases, Immune deficiency, Active malignancy, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Variable (until disease progression)

37 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a chemotherapy treatment called FOLFIRINOX for patients with untreated metastatic pancreatic cancer. Researchers aim to determine the treatment's safety and potential side effects. The trial seeks participants aged 65 or older who have been recently diagnosed with this cancer and have at least one other affected area in the body. Participants should be able to perform daily activities without major difficulty and must not have received other treatments for this advanced cancer. As a Phase 2 trial, this 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 information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that FOLFIRINOX, a type of chemotherapy, has been tested for safety in people with pancreatic cancer. One study found that patients using FOLFIRINOX lived longer than those using gemcitabine, suggesting its effectiveness in treating pancreatic cancer.

However, side effects are important to consider. FOLFIRINOX can cause nausea, fatigue, and low blood counts, which are common with chemotherapy. Most patients manage these side effects with support from their medical team.

FOLFIRINOX is already a standard treatment for some types of pancreatic cancer, indicating its general safety. While these studies offer reassurance about its use, patients should discuss any concerns with their healthcare providers. ^{1 2 3 4 5}

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

FOLFIRINOX is unique because it combines four chemotherapy drugs: Oxaliplatin, Leucovorin, 5-Fluorouracil, and Irinotecan, to tackle pancreatic cancer more aggressively. Unlike the standard treatment options, which often include gemcitabine-based therapies, this regimen offers a multi-pronged attack, potentially enhancing the overall effectiveness against cancer cells. Researchers are excited about FOLFIRINOX because it has shown promise in improving survival rates by targeting multiple pathways that cancer cells use to grow and spread, offering hope for better outcomes in this challenging disease.

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

Research has shown that FOLFIRINOX, the treatment under study in this trial, can effectively treat advanced pancreatic cancer. One study found that patients taking FOLFIRINOX lived for a median of 11.1 months, compared to 6.8 months for those taking gemcitabine. Additionally, 47.8% of patients on FOLFIRINOX experienced tumor reduction or disappearance. These results suggest that FOLFIRINOX could be a promising option for improving survival in this condition. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for people over 65 with a specific type of untreated pancreatic cancer that has spread. They must have finished any previous radiation at least 2 weeks before and any adjuvant therapy over 6 months prior to consent. Participants need good organ function, understand English, be able to complete assessments, and use effective contraception if applicable.

Inclusion Criteria

Patients must be fluent in English and must be able and willing to undergo Comprehensive Geriatric Assessment

My blood tests show my organs and bone marrow are working well.

I am 65 years old or older.

Exclusion Criteria

You are not currently receiving or have not previously received any other experimental treatment for advanced pancreatic cancer.

I do not have any severe illnesses that could interfere with the study.

My cancer is a type of pancreatic cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an alternating regimen of FOLFOX and FOLFIRI every 28 days until disease progression or other conditions apply

Variable (until disease progression)

Visits on day 1 and day 14 of each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• FOLFIRINOX

Trial Overview The study tests the effectiveness of alternating FOLFOX and FOLFIRI chemotherapy regimens in older patients with metastatic pancreatic cancer. It aims to evaluate how well they tolerate this treatment combination and what toxic effects may occur.

How Is the Trial Designed?

Group I: Experimental: FOLFIRINOX Experimental Treatment 1 Intervention

FOLFIRINOX: Oxaliplatin, Leucovorin and 5-Fluorouracl, Irinotecan,

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

Approved in European Union as FOLFIRINOX for:

• Advanced pancreatic cancer

Approved in United States as FOLFIRINOX for:

• Metastatic pancreatic cancer

Who Is Running the Clinical Trial?

Fox Chase Cancer Center

Lead Sponsor

Trials

236

Recruited

39,300+

Published Research Related to This Trial

In a study of 71 patients with advanced pancreatic cancer who progressed after initial treatment with modified FOLFIRINOX, second-line chemotherapy resulted in a 7.1% partial response rate and a 27.1% disease stabilization rate.

The median overall survival for these patients was 6.2 months, with CA19.9 levels above the normal limit indicating worse survival outcomes, suggesting that certain prognostic factors can help identify patients who may benefit more from salvage chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second-line therapy for advanced pancreatic cancer: evaluation of prognostic factors and review of current literature. Caparello, C., Vivaldi, C., Fornaro, L., et al.[2022]

Neoadjuvant FOLFIRINOX treatment in patients with borderline resectable pancreatic cancer (BRPC) resulted in a median overall survival of 22.2 months and a high resection rate of 67.8%, indicating its potential effectiveness in this patient group.

The treatment was associated with manageable adverse events, with the most common being neutropenia, diarrhea, and fatigue, but no deaths were reported due to FOLFIRINOX, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant FOLFIRINOX in Patients With Borderline Resectable Pancreatic Cancer: A Systematic Review and Patient-Level Meta-Analysis. Janssen, QP., Buettner, S., Suker, M., 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 399 patients with advanced pancreatic cancer receiving FOLFIRINOX treatment, 13% experienced febrile neutropenia (FN) and 27% experienced grade 4 (G4) neutropenia, primarily during the first two treatment cycles.

Key risk factors for developing FN and G4 neutropenia included having total bilirubin levels above the normal range and not modifying the treatment dose from the original regimen, highlighting the importance of monitoring these factors during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX in Pancreatic Cancer: Risk Factors for Febrile Neutropenia and Severe Neutropenia - Nationwide Study Analysis. Todaka, A., Sasaki, M., Ueno, H., et al.[2023]

FOLFIRINOX, a combination chemotherapy regimen, has been shown to significantly improve overall survival and progression-free survival in patients with metastatic pancreatic cancer compared to the traditional treatment with gemcitabine, based on results from the PRODIGE 4/ACCORD 11 trial.

While FOLFIRINOX is associated with higher toxicity rates, including febrile neutropenia and diarrhea, its rapid adoption in clinical practice highlights its effectiveness, and further studies are needed to explore its benefits in other treatment settings like second-line therapy and adjuvant chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status on the place of FOLFIRINOX in metastatic pancreatic cancer and future directions. Lambert, A., Gavoille, C., Conroy, T.[2021]

In a study of 284 patients with locally advanced or metastatic pancreatic cancer treated with FOLFIRINOX, the objective response rates were 14.0% for LAPC and 18.2% for metastatic PDAC, indicating modest effectiveness in both groups.

Median overall survival was 12.7 months for LAPC patients and 8.1 months for metastatic PDAC patients, with significant improvements in 2-year survival probabilities after one year of treatment, highlighting the potential long-term benefits of FOLFIRINOX.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Response and Conditional Survival in Advanced Pancreatic Cancer Patients Treated with FOLFIRINOX: A Multicenter Cohort Study. van der Sijde, F., van Dam, JL., Groot Koerkamp, B., 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]

Modified-FOLFIRINOX (mFOLFIRINOX) significantly improves safety and tolerability for Chinese patients with locally advanced pancreatic cancer (LAPC), with a response rate of 37.1% and common severe side effects including neutropenia and anemia.

Patients with LAPC who received neoadjuvant therapy with mFOLFIRINOX and subsequently underwent surgery had a median overall survival of 27.7 months, which is significantly better than the 8.9 months seen in patients who had upfront surgery without prior chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Modified-FOLFIRINOX-Regimen-Based Neoadjuvant Therapy with Outcomes of Locally Advanced Pancreatic Cancer in Chinese Population. Li, X., Guo, C., Li, Q., et al.[2023]

In a study of 69 chemotherapy-naïve patients with metastatic pancreatic cancer, the modified FOLFIRINOX regimen resulted in a median overall survival of 11.2 months and a response rate of 37.7%, indicating its efficacy in this patient population.

The modified regimen demonstrated a better safety profile compared to previous studies, with a 47.8% incidence of grade 3 or higher neutropenia and fewer serious adverse events, suggesting it can be administered without prophylactic pegfilgrastim.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of modified FOLFIRINOX for chemotherapy-naïve patients with metastatic pancreatic cancer. Ozaka, M., Ishii, H., Sato, T., et al.[2019]

In a phase II study involving 36 chemotherapy-naïve Japanese patients with metastatic pancreatic cancer, the FOLFIRINOX regimen demonstrated a response rate of 38.9% and a median overall survival of 10.7 months, indicating its efficacy in this population.

The treatment was associated with significant toxicities, including high rates of neutropenia (77.8%) and febrile neutropenia (22.2%), but no treatment-related deaths were reported, suggesting that while FOLFIRINOX is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of FOLFIRINOX for chemotherapy-naïve Japanese patients with metastatic pancreatic cancer. Okusaka, T., Ikeda, M., Fukutomi, A., et al.[2022]

FOLFIRINOX, a chemotherapy regimen combining 5-fluorouracil, irinotecan, and oxaliplatin, significantly improves overall survival (11.1 months) and progression-free survival (6.4 months) compared to gemcitabine (6.8 months and 3.3 months, respectively) in patients with metastatic pancreatic cancer, based on a trial with 342 participants.

While FOLFIRINOX is more effective and cost-effective than gemcitabine, it is associated with higher rates of severe side effects, such as neutropenia and diarrhea, necessitating careful patient selection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A New Direction for Pancreatic Cancer Treatment: FOLFIRINOX in Context. Kindler, HL.[2020]

In a study of 243 patients with advanced pancreatic adenocarcinoma treated with FOLFIRINOX, the relative dose intensity (RDI) of the treatment agents did not significantly correlate with disease control or objective response, suggesting that dose reductions may not compromise treatment effectiveness.

The median cumulative multi-drug RDI was 80%, and including RDI in predictive models did not enhance the ability to forecast disease control, indicating that oncologists can safely adjust doses without fearing a loss of therapeutic benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX relative dose intensity and disease control in advanced pancreatic adenocarcinoma. Vary, A., Lebellec, L., Di Fiore, F., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7081111/

FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in ... Detailed outcomes data are summarized in Table 2. The objective response rate was 47.8% in the FOLFIRINOX group, compared to 37.1% in the ...

2. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2795978

Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as ... This randomized clinical trial examines 5-year outcomes and prognostic factors for overall survival for treatment with modified FOLFIRINOX ...

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

Real Life Data and Outcome of FOLFIRINOX Use in ... Results: The results showed a median overall survival of 228 days (IQR 118-355). Only 14.0% (n = 12) completed the first-line treatment, and 51.2% (n = 44) of ...

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

FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic ... Results. The median overall survival was 11.1 months in the FOLFIRINOX group as compared with 6.8 months in the gemcitabine group (hazard ratio for death, 0.57; ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e16393

Efficacy and safety of FOLFIRINOX versus gemcitabine- ... Results: FOLFIRINOX-treated patients (n = 3,020) demonstrated significantly longer overall survival (OS) than gemcitabine-treated patients (n = ...

6. cancertherapyadvisor.com cancertherapyadvisor.com/news/folfirinox-standard-care-pancreatic-cancer/

FOLFIRINOX Deemed Standard Care for Locally Advanced ... The 12-month OS rate was 61.2% in the FOLFIRINOX arm and 60.5% in the gemcitabine arm. The 36-month OS rates were 11.8% and 12.3%, respectively.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9087258/

Efficacy and safety of FOLFIRINOX as second-line ... FOLFIRINOX is recommended as a second-line chemotherapy regimen for patients with pancreatic cancer that have failed on gemcitabine-based first-line therapy.