Surgery for Pancreatic Cancer with Liver Metastases

(PDAC-LIV Trial)

Recruiting at 1 trial location

Overseen By Alexandre Brind'Amour, MD, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Laval University

Must be taking: FOLFIRINOX

Disqualifiers: Advanced disease, >3 liver metastases, others

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: 5

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment plan for individuals with pancreatic cancer that has spread to the liver. It combines surgery with a chemotherapy regimen called FOLFIRINOX (also known as FOLFOXIRI). The goal is to determine if this approach better manages the cancer by first shrinking tumors with chemotherapy and then surgically removing them. Suitable candidates are those with a confirmed diagnosis of pancreatic cancer and no more than three liver metastases that can be surgically removed.

As an unphased trial, this study provides patients the opportunity to explore innovative treatment options that may improve their outcomes.

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, since the trial involves chemotherapy with FOLFIRINOX, it's important to discuss your current medications with the trial team to ensure there are no interactions.

What prior data suggests that this surgical method is safe for treating pancreatic cancer with liver metastases?

Research has shown that FOLFIRINOX, a type of chemotherapy, is usually well-tolerated by patients. In studies, those treated with FOLFIRINOX lived longer than those who received other treatments like gemcitabine. However, patients often experience side effects such as nausea, fatigue, and low blood cell counts.

Evidence suggests that surgery, including operations on the pancreas and liver, is safe when carefully planned. Patients selected for surgery often achieve better outcomes, but the risk depends on their overall health and the extent of cancer spread.

While both treatments carry risks, they also offer potential benefits for eligible patients. Discuss the pros and cons with a doctor to determine the best approach for your specific situation. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about FOLFIRINOX for pancreatic cancer with liver metastases because it combines multiple chemotherapy agents to aggressively target cancer cells. Unlike traditional treatments that may focus on just one or two drugs, FOLFIRINOX uses a combination of four drugs—fluorouracil, leucovorin, irinotecan, and oxaliplatin—that work together to enhance effectiveness. This approach has the potential to improve outcomes by attacking the cancer cells from different angles, which could be more effective than standard chemotherapy regimens.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer with liver metastases?

Studies have shown that FOLFIRINOX, a type of chemotherapy, can significantly improve survival for patients with metastatic pancreatic cancer. One study found that patients treated with FOLFIRINOX lived for a median of 11.1 months, compared to 6.8 months for those treated with gemcitabine, another common chemotherapy. Some reports even indicate that FOLFIRINOX can completely clear cancer that has spread to the liver. In this trial, participants will undergo surgery to remove tumors in the pancreas and liver, which has shown promise, with some patients living longer. Together, these treatments may offer hope for combating pancreatic cancer that has spread to the liver. ^{2 3 5 6 7}

Who Is on the Research Team?

Alexandre Brind'Amour, MD, MSc

Principal Investigator

CHU de Québec

Are You a Good Fit for This Trial?

This trial is for patients with pancreatic cancer that has spread to the liver, who have not more than three liver metastases and are deemed operable. They must show a response to FOLFIRINOX chemotherapy as evidenced by imaging and blood tumor markers.

Inclusion Criteria

I had a liver surgery or don't need it due to successful chemotherapy.

I haven't developed new cancer spread after my initial chemo.

I am fit for surgery to remove part of my pancreas.

Exclusion Criteria

My cancer has spread beyond my liver.

I have more than 3 liver metastases.

I cannot receive FFX due to health reasons.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Neoadjuvant Treatment

Participants receive 12 cycles of perioperative FOLFIRINOX, with reassessment after the first 6 cycles

Approximately 24 weeks

Regular visits for treatment and reassessment

Surgery

Pancreatic resection and liver metastases excision for patients with tumor response

1 week

1 visit (in-person)

Follow-up

Participants are monitored with blood tumor markers and CT-scan every three months for two years, and every four months afterwards or until recurrence

3 years

Regular visits every 3-4 months

What Are the Treatments Tested in This Trial?

Interventions

• FOLFIRINOX
• Pancreatic resection and non-anatomic liver resections

Trial Overview

The study tests if surgery to remove both the pancreatic tumor and up to three liver metastases after or during cycles of FOLFIRINOX chemotherapy can be beneficial. Patients will undergo detailed scans and receive up to 12 cycles of chemo before and/or after surgery.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 1 Intervention

Patients will undergo surgery for primary pancreatic cancer and liver metastases.

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?

Laval University

Lead Sponsor

Trials

439

Recruited

178,000+

Published Research Related to This Trial

A patient with pancreatic ductal adenocarcinoma and a solitary liver metastasis showed a favorable response to nine cycles of FOLFIRINOX therapy, which is a combination chemotherapy regimen.

After surgery that included distal pancreatectomy and hepatectomy, the patient remained disease-free for 2 years post-operation and 28 months after the initial diagnosis, suggesting the potential effectiveness of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of metastatic pancreatic adenocarcinoma with prolonged survival after combination of neoadjuvant FOLFIRINOX therapy and synchronous distal pancreatectomy and hepatectomy. Neofytou, K., Giakoustidis, A., Smyth, EC., et al.[2015]

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 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]

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 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 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 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 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]

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]

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 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]

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]

A patient with metastatic pancreatic adenocarcinoma underwent neoadjuvant FOLFIRINOX chemotherapy followed by a combined surgical resection of the pancreas and liver.

Four years after diagnosis, the patient remains disease-free, suggesting that this aggressive treatment approach may be effective in managing advanced pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Disease-free Survival Following Combination Multi-visceral and Metastatic Resection with Neoadjuvant FOLFIRINOX for Pancreatic Adenocarcinoma: A Case Report. Sodergren, M., Brammer, K., Cunningham, D., et al.[2020]

Citations

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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; ...

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wjso.biomedcentral.com

wjso.biomedcentral.com/articles/10.1186/s12957-021-02291-6

The role of FOLFIRINOX in metastatic pancreatic cancer

We found that FOLFIRINOX could directly improve OS rate of patients with metastatic PC (HR 0.76, 95% Cl 0.67–0.86, p<0.001) but had no benefit ...

6.

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 ...

7.

jamanetwork.com

jamanetwork.com/journals/jamaoncology/fullarticle/2795978

Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as ...

001), and 5-year overall survival was 43.2% vs 31.4%; median metastasis-free survival was 29.4 months (95% CI, 21.4-40.1) vs 17.7 months (95% CI ...