FOLFIRINOX Chemotherapy for Metastatic Pancreatic Cancer

Overseen By Jin He, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must be taking: FOLFIRINOX

Disqualifiers: HIV, Hepatitis B/C, Cardiovascular, 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)

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

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

Trial Summary

What is the purpose of this trial?

Surgical Resection of Synchronous Pulmonary or Hepatic Oligometastatic Pancreatic Ductal Adenocarcinoma (PHOLIPANC). This is an interventional, open-label, non-randomised, single-arm phase II clinical trial. Eligible patients with hepatic or pulmonary oligometastatic adenocarcinoma of the pancreas must have received neoadjuvant FOLFIRINOX chemotherapy in cycles of 14 days, or other clinically indicated alternative. FOLFIRINOX is not a study treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does allow patients who are already on FOLFIRINOX or modified FOLFIRINOX to continue, as long as they haven't had more than two treatments.

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

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

Is FOLFIRINOX chemotherapy generally safe for humans?

FOLFIRINOX chemotherapy has been shown to be effective but can cause serious side effects like neutropenia (low white blood cell count), febrile neutropenia (fever with low white blood cell count), and diarrhea. These side effects are common, so careful monitoring and dose adjustments are often necessary to manage them safely. ^{2 6 7 8 9}

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

FOLFIRINOX is unique because it combines four chemotherapy drugs (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) and is used as a first-line treatment for advanced pancreatic cancer, offering a more aggressive approach compared to other regimens. It is particularly effective for patients with good performance status, meaning they are still relatively healthy despite their cancer. ^{4 10 11 12 13}

Research Team

Jin He, MD, PhD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for adults over 18 with a specific type of pancreatic cancer that has spread to the liver or lungs but hasn't been treated yet. They must have a certain level of physical fitness and measurable disease as per imaging scans reviewed by a qualified radiologist.

Inclusion Criteria

I am legally able to consent to join the clinical trial.

I am eligible for FOLFIRINOX chemotherapy.

My pancreatic cancer has spread only to my liver or lungs and hasn't been treated yet.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive neoadjuvant FOLFIRINOX chemotherapy in cycles of 14 days

8-16 weeks

Surgical Resection

Eligible patients undergo surgical resection of the primary tumor and metastases

2-6 weeks after last chemotherapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 months

Treatment Details

Interventions

• FOLFIRINOX

Trial Overview The study is testing FOLFIRINOX chemotherapy in patients before surgery (neoadjuvant) to see how it affects pancreatic cancer that has spread to the liver or lungs. It's an open-label, single-arm Phase II trial, meaning everyone gets the same treatment and knows what it is.

Participant Groups

Group I: Treatment arm liver/lung oligometastasis Experimental Treatment 1 Intervention

Eligible patients with hepatic or pulmonary oligometastatic adenocarcinoma of the pancreas must have received neoadjuvant FOLFIRINOX chemotherapy in cycles of 14 days, or other clinically indicated alternative. FOLFIRINOX is not a study treatment. Patients with pulmonary metastasis with tumor response or stable disease and a resectable primary tumor after the first 4 cycles can undergo resection of the primary tumor followed by resection of pulmonary metastases or vice versa, if feasible.Patients with hepatic metastasis with tumor response or stable disease and a resectable primary tumor can undergo explorative laparotomy and synchronous resection of the tumor and hepatic metastases, if feasible. In patients who undergo exploratory laparotomy and are deemed to have unresectable disease by the surgeon, the patient may receive 4 more cycles of neoadjuvant chemotherapy 2-4 week after surgery, before the patient will be re-evaluated for the eligibility for the Study Entry Screening.

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?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Findings from Research

In a study of 102 patients with locally advanced and metastatic pancreatic cancer, FOLFIRINOX treatment showed promising efficacy, with median overall survival of 13.1 months for metastatic patients and 23 months for locally advanced patients when using modified doses.

Despite the efficacy of dose-modified FOLFIRINOX, safety concerns were highlighted, as 43% of patients experienced severe hematologic adverse events, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX for advanced pancreatic cancer: the Princess Margaret Cancer Centre experience. Chllamma, MK., Cook, N., Dhani, NC., 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 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 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]

In a multicenter phase II study involving 31 patients with locally advanced pancreatic cancer (LAPC) and 44 with metastatic pancreatic cancer (MPC), modified FOLFIRINOX showed comparable efficacy to full-dose FOLFIRINOX in MPC, with a response rate of 35.1% and a median overall survival of 10.2 months.

The study found that modified FOLFIRINOX significantly reduced adverse events such as neutropenia, vomiting, and fatigue, while demonstrating notable efficacy in LAPC with a median progression-free survival of 17.8 months and overall survival of 26.6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer. Stein, SM., James, ES., Deng, Y., et al.[2022]

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 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 study involving 65 Chinese patients with metastatic pancreatic cancer, the modified FOLFIRINOX regimen demonstrated a 32.3% objective response rate and a 73.8% disease control rate, indicating its efficacy as a first-line treatment.

The modified regimen was well-tolerated, with major grade 3 or 4 adverse events occurring in only a small percentage of patients (12.3% neutropenia and 6.2% diarrhea), and no treatment-related deaths were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of modified FOLFIRINOX as first-line chemotherapy for Chinese patients with metastatic pancreatic cancer. Wang, ZQ., Zhang, F., Deng, T., 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 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]

In a pilot study of 14 patients with resectable pancreatic cancer, treatment with 4 cycles of neoadjuvant FOLFIRINOX resulted in varying degrees of tumor regression, with 28.6% of patients showing significant tumor destruction (Evans grade III).

The study highlights the heterogeneity of pancreatic cancer responses to FOLFIRINOX, indicating that while some patients benefit significantly, others do not, suggesting the need for further research on optimal treatment duration and standardized grading for better comparison.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathologic Response to Primary Systemic Therapy With FOLFIRINOX in Patients With Resectable Pancreatic Cancer. Polish, A., Joseph, NE., Marsh, RW.[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]

References

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

FOLFIRINOX for advanced pancreatic cancer: the Princess Margaret Cancer Centre experience. [2022]

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

A New Direction for Pancreatic Cancer Treatment: FOLFIRINOX in Context. [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. Egypt pubmed.ncbi.nlm.nih.gov

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

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

Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer. [2022]

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

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

7. England pubmed.ncbi.nlm.nih.gov

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

8. Greece pubmed.ncbi.nlm.nih.gov

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

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

The efficacy and safety of modified FOLFIRINOX as first-line chemotherapy for Chinese patients with metastatic pancreatic cancer. [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. England pubmed.ncbi.nlm.nih.gov

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

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

Pathologic Response to Primary Systemic Therapy With FOLFIRINOX in Patients With Resectable Pancreatic Cancer. [2020]

13. 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]