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

Trial Summary

What is the purpose of this trial?

This trial tests alternating chemotherapy treatments for patients over 65 with newly diagnosed metastatic pancreatic cancer. The goal is to see how well these treatments are tolerated and how effective they are. The drugs work by attacking and killing cancer cells to slow down or stop the cancer from spreading.

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.

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

Research shows that FOLFIRINOX significantly improves survival and quality of life for patients with advanced pancreatic cancer compared to the previous standard treatment, gemcitabine. In a study with 342 patients, those treated with FOLFIRINOX lived longer and had better outcomes, although they experienced more side effects. ^{1 2 3 4 5}

Is FOLFIRINOX safe for treating pancreatic cancer?

FOLFIRINOX is generally considered safe for treating pancreatic cancer, but it can cause serious side effects like neutropenia (low white blood cell count), febrile neutropenia (fever with low white blood cell count), and diarrhea. Careful monitoring and dose adjustments are often needed to manage these side effects. ^{1 3 6 7 8}

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

FOLFIRINOX is unique because it combines four drugs (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) and is used as a first-line treatment for advanced pancreatic cancer, especially in patients who are fit enough to handle its intensity. It is known for its effectiveness in improving survival rates compared to other treatments, although it can have more severe side effects. ^{2 9 10 11 12}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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]

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 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]

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]

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]

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 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]

References

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

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

2. 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]

3. Germany pubmed.ncbi.nlm.nih.gov

A phase II study of modified FOLFIRINOX for chemotherapy-naïve patients with metastatic pancreatic cancer. [2019]

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

Association of Modified-FOLFIRINOX-Regimen-Based Neoadjuvant Therapy with Outcomes of Locally Advanced Pancreatic Cancer in Chinese Population. [2023]

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

Current status on the place of FOLFIRINOX in metastatic pancreatic cancer and future directions. [2021]

6. England pubmed.ncbi.nlm.nih.gov

FOLFIRINOX relative dose intensity and disease control in advanced pancreatic adenocarcinoma. [2022]

7. Greece pubmed.ncbi.nlm.nih.gov

FOLFIRINOX in Pancreatic Cancer: Risk Factors for Febrile Neutropenia and Severe Neutropenia - Nationwide Study Analysis. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Phase II study of FOLFIRINOX for chemotherapy-naïve Japanese patients with metastatic pancreatic cancer. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Second-line therapy for advanced pancreatic cancer: evaluation of prognostic factors and review of current literature. [2022]

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

Neoadjuvant FOLFIRINOX in Patients With Borderline Resectable Pancreatic Cancer: A Systematic Review and Patient-Level Meta-Analysis. [2021]

11. Egypt pubmed.ncbi.nlm.nih.gov

Treatment Response and Conditional Survival in Advanced Pancreatic Cancer Patients Treated with FOLFIRINOX: A Multicenter Cohort Study. [2022]

12. 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]