Chemotherapy for Pancreatic Cancer

(NeoPancOne Trial)

Recruiting at 7 trial locations

Overseen By Anna Dodd

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Must be taking: mFFX

Must not be taking: QT prolonging medications

Disqualifiers: Metastatic disease, Unresectable PDAC, Active hepatitis, 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)

Compensation: Varies

Number of Visits: Unknown

84 Participants Needed

Trial Summary

What is the purpose of this trial?

To date, there have been no Canadian led neoadjuvant or peri-operative trials, this multicentre design gives the opportunity to build more experience with this strategy across Canada in more institutions. The design of this prospective trial will also test our important hypotheses regarding the use of biomarkers to understand the benefit of mFFX in improving outcomes for patients with resectable pancreas cancer. Data from this study would likely inform future studies where patients are given personalised options for the best treatment strategies rather than one empiric approach.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on certain medications like coumadin (a blood thinner) and cannot switch to another type, you may not be eligible to participate.

What data supports the effectiveness of the drug Modified FOLFIRINOX (mFFX) for pancreatic cancer?

Research shows that Modified FOLFIRINOX (mFFX) is effective as a first-line treatment for advanced pancreatic cancer, with studies comparing its efficacy and safety to other treatments like SOXIRI and standard-dose FOLFIRINOX. It has been shown to be effective in patients with specific genetic markers, such as BRCA mutations, which may influence the treatment's success. ^{1 2 3 4 5}

Is modified FOLFIRINOX (mFFX) safe for humans?

Modified FOLFIRINOX (mFFX) is generally used with a reduced dosage to lower the risk of side effects compared to the original version, which is known to be more toxic. Studies have shown that mFFX is used in practice to manage safety concerns, especially for patients with pancreatic cancer. ^{3 4 5 6 7}

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

Modified FOLFIRINOX (mFFX) is a chemotherapy treatment for pancreatic cancer that uses a reduced dosage of the original FOLFIRINOX regimen to decrease toxicity while maintaining effectiveness. It includes a combination of four drugs: fluorouracil, leucovorin, irinotecan, and oxaliplatin, and is considered a first-line treatment for advanced pancreatic cancer. ^{1 3 4 5 7}

Research Team

Jennifer J. Knox, MD, MSc

Principal Investigator

Princess Margaret Cancer Centre, University Health Network

Eligibility Criteria

This trial is for adults over 18 with confirmed pancreatic ductal adenocarcinoma (PDAC) that can be surgically removed. They must be fit for surgery and the mFFX chemotherapy, have no prior cancer treatments, and no evidence of metastases or other primary cancers in the last 3 years. Participants need proper liver and blood function, not be pregnant or breastfeeding, agree to use contraception if applicable, and provide consent.

Inclusion Criteria

My doctor agrees I can handle mFFX treatment.

My cancer has not spread to major arteries near my liver and stomach.

I have been diagnosed with pancreatic cancer, confirmed by a specific biopsy.

Exclusion Criteria

I have a history of heart rhythm issues or take medication that affects my heart rhythm.

My pancreatic cancer cannot be removed by surgery, as confirmed by scans.

I've had two unsuccessful attempts to confirm pancreatic cancer through EUS-FNB.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neo-adjuvant Chemotherapy

Participants receive neo-adjuvant mFFX chemotherapy for up to 6 cycles

12-18 weeks

Surgery

Participants undergo surgery for resectable pancreatic adenocarcinoma

Adjuvant Chemotherapy

Participants receive adjuvant chemotherapy for up to 6 cycles

12-18 weeks

Follow-up

Participants are monitored for disease-free survival and other outcomes

2-4 years

Treatment Details

Interventions

• Modified Folforinox (mFFX)

Trial Overview The study tests how well patients with resectable pancreatic cancer respond to a chemotherapy regimen called modified Folforinox (mFFX) before and after surgery. It also examines whether GATA6 expression levels can predict treatment outcomes. This Canadian multicentre trial aims to personalize future treatment strategies.

Participant Groups

Group I: Neo-adjuvant mFFX Experimental Treatment 1 Intervention

Neo-adjuvant mFFX up to 6 cycles, surgery, adjuvant chemotherapy for up tp 6 cycles, follow up

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Pancreatic Cancer Canada

Collaborator

Trials

2

Recruited

100+

Findings from Research

In a study of 198 patients with advanced pancreatic cancer, the SOXIRI chemotherapy regimen showed similar overall survival (12.1 months) and progression-free survival (6.5 months) compared to the standard mFOLFIRINOX regimen (11.2 months and 6.8 months, respectively), indicating comparable efficacy.

While both regimens had similar safety profiles, SOXIRI was associated with a higher incidence of anemia (41.4% vs. 24%), suggesting that while effective, it may have specific side effects that need to be monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of SOXIRI versus mFOLFIRINOX in advanced pancreatic cancer. Li, X., Huang, J., Wang, F., et al.[2023]

Modified-dose FOLFIRINOX (mFOLFIRINOX) demonstrated comparable efficacy to standard-dose FOLFIRINOX (sFOLFIRINOX) in treating pancreatic cancer, with similar objective response rates and overall survival outcomes among 130 patients studied.

mFOLFIRINOX was associated with significantly lower rates of severe adverse events, such as neutropenia, anorexia, and diarrhea, suggesting it is a safer option for patients who may be concerned about toxicity while maintaining effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer. Kang, H., Jo, JH., Lee, HS., et al.[2022]

In a study of 54 patients with advanced pancreatic cancer, S-IROX showed a higher disease control rate (73.7%) compared to modified FOLFIRINOX (mFFX) (62.2%), indicating it may be more effective as a second-line treatment after gemcitabine plus nab-paclitaxel.

Both S-IROX and mFFX had similar overall survival rates (14.2 months for S-IROX and 11.5 months for mFFX) and tolerability, with no significant differences in severe side effects, suggesting both regimens are viable options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective comparative study of S-IROX and modified FOLFIRINOX for patients with advanced pancreatic cancer refractory to gemcitabine plus nab-paclitaxel. Saito, K., Nakai, Y., Takahara, N., et al.[2022]

The modified FOLFIRINOX (mFOLFIRINOX) regimen demonstrated a high treatment efficacy in patients with locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer (MPC), achieving a response rate of 55.2% among 29 evaluable patients.

The treatment was well-tolerated, with only 9 patients experiencing grade 3 or 4 adverse effects, and no patients discontinued treatment due to side effects, indicating a favorable safety profile for this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Modified FOLFIRINOX for advanced pancreatic cancer: a tertiary center experience from China]. Bai, X., Su, R., Ma, T., et al.[2018]

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 318 patients with metastatic pancreatic cancer, the modified FOLFIRINOX (mFFX) regimen showed similar overall survival and progression-free survival compared to the original FOLFIRINOX (oFFX) regimen, indicating that mFFX is just as effective.

mFFX was associated with significantly fewer adverse events, such as thrombopenia and liver dysfunction, making it a safer option for patients compared to oFFX.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Retrospective Analysis of Original versus Modified FOLFIRINOX in Metastatic Pancreatic Cancer: Results of the NAPOLEON Study. Nakazawa, J., Tsuruta, N., Shimokawa, M., et al.[2023]

References

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

Efficacy and safety of SOXIRI versus mFOLFIRINOX in advanced pancreatic cancer. [2023]

2. Japan pubmed.ncbi.nlm.nih.gov

Association between BRCA Gene Variants and the Response to Modified FOLFIRINOX in Patients with Unresectable Pancreatic Cancer. [2023]

3. China pubmed.ncbi.nlm.nih.gov

Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer. [2022]

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

A retrospective comparative study of S-IROX and modified FOLFIRINOX for patients with advanced pancreatic cancer refractory to gemcitabine plus nab-paclitaxel. [2022]

5. China pubmed.ncbi.nlm.nih.gov

[Modified FOLFIRINOX for advanced pancreatic cancer: a tertiary center experience from China]. [2018]

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

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

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

Multicenter Retrospective Analysis of Original versus Modified FOLFIRINOX in Metastatic Pancreatic Cancer: Results of the NAPOLEON Study. [2023]