NP137 + FOLFIRINOX for Pancreatic Cancer

Overseen By Aram Hezel

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Nabeel Badri

Disqualifiers: Metastatic cancer, Peripheral neuropathy, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

25 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the treatment NP137 + FOLFIRINOX for pancreatic cancer?

FOLFIRINOX is a standard treatment for advanced pancreatic cancer and has shown effectiveness in improving survival rates in patients with good health status. It is used as a first-line treatment for advanced cases and has been evaluated for its response rates and survival benefits in various studies. ^{1 2 3 4 5}

What safety data exists for NP137 + FOLFIRINOX treatment in humans?

FOLFIRINOX, a treatment used for pancreatic cancer, is known to cause significant side effects that often require dose adjustments or stopping the treatment. Modifications to the FOLFIRINOX regimen have been shown to improve safety and tolerability in some patients. ^{1 6 7 8 9}

How is the NP137 + FOLFIRINOX treatment different from other pancreatic cancer treatments?

The NP137 + FOLFIRINOX treatment is unique because it combines NP137, a novel agent, with FOLFIRINOX, which is a standard chemotherapy regimen for advanced pancreatic cancer. This combination may offer a new approach by potentially enhancing the effectiveness of FOLFIRINOX, which is already known for its activity in treating pancreatic cancer, although it can be quite toxic. ^{1 3 4 10 11}

What is the purpose of this trial?

The objective of this study is to investigate whether adding the study drug, NP137, to a patient's treatment regimen (before surgery and in combination with chemotherapy afterward) can alter the behavior of pancreatic cancer..

Research Team

Aram Hezel

Principal Investigator

University of Rochester

Eligibility Criteria

This trial is for individuals with pancreatic cancer that can potentially be removed by surgery. Specific details about who can join are not provided, but typically participants need to meet certain health standards and have a type of cancer the study targets.

Inclusion Criteria

Written informed consent to participate in the trial

I have not had any treatment for pancreatic cancer before.

Subjects of childbearing potential must have a negative urine or serum pregnancy test prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required for enrollment

Exclusion Criteria

I don't have any health issues that would make it unsafe for me to take a new drug.

I haven't had a serious infection or been on antibiotics for an infection in the last 2 weeks.

I have another cancer but it won't need treatment in the next 2 years, except for some exceptions like superficial bladder cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-surgical Treatment

Participants receive two doses of NP137 approximately two weeks apart, followed by surgery

4 weeks

Post-surgical Treatment

Participants receive FOLFIRINOX combined with NP137 for about 6 months

6 months

NP137 Extension Treatment

Participants receive an additional 6 months of treatment with only NP137

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

5-8 years

Treatment Details

Interventions

• NP137

Trial Overview The trial is testing NP137 given before surgery and combined with FOLFIRINOX chemotherapy after surgery. The goal is to see if this treatment approach changes how pancreatic cancer behaves or responds.

Participant Groups

Group I: Treatment Experimental Treatment 1 Intervention

Patient receive two doses of the study drug, NP137, approximately two weeks apart. This will be followed by surgery. After the surgery if feasible, patients will begin post-surgical treatment with a standard-of-care chemotherapy regimen called FOLFIRINOX, combined with the study drug, NP137, for a total duration of about 6 months. Upon completing this phase, patients will receive an additional 6 months of treatment with only the study drug NP137.

Who Is Running the Clinical Trial?

Nabeel Badri

Lead Sponsor

Trials

1

Recruited

30+

Aram Hezel

Lead Sponsor

Trials

1

Recruited

30+

NETRIS Pharma

Industry Sponsor

Trials

7

Recruited

530+

Findings from Research

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]

In a phase II trial involving 48 patients with gemcitabine-refractory unresectable pancreatic cancer, modified FOLFIRINOX demonstrated promising efficacy with an objective response rate of 18.8% and a disease control rate of 62.5%.

The treatment was associated with manageable safety concerns, primarily neutropenia (64.6% of patients), but most non-hematologic adverse events were mild, indicating that while effective, careful monitoring for hematologic toxicities is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase II trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer. Chung, MJ., Kang, H., Kim, HG., 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]

FOLFIRINOX (FFX) has been shown to significantly improve median overall survival, progression-free survival, and objective response rates in patients with metastatic pancreatic cancer compared to gemcitabine, as established in the PRODIGE 4/ACCORD 11 study.

Despite initial concerns about its toxicity, FFX has been widely adopted in clinical practice, leading to new research opportunities and discussions about managing its side effects and optimizing treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreatic cancer and FOLFIRINOX: a new era and new questions. Marsh, Rde W., Talamonti, MS., Katz, MH., et al.[2023]

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]

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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer: An intention to treat analysis. [2019]

3. 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]

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. China pubmed.ncbi.nlm.nih.gov

Multicenter phase II trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer. [2020]

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

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

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

Pancreatic cancer and FOLFIRINOX: a new era and new questions. [2023]

8. 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]

9. Germany pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics of FOLFIRINOX: a review of studies and parameters. [2019]

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

Resectability After First-Line FOLFIRINOX in Initially Unresectable Locally Advanced Pancreatic Cancer: A Single-Center Experience. [2022]

11. China pubmed.ncbi.nlm.nih.gov

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