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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding a drug called NP137, an experimental treatment, to the usual pancreatic cancer treatment can alter cancer behavior. Patients will receive NP137 before surgery and, if possible, continue with it alongside standard chemotherapy after surgery. The trial seeks individuals with surgically removable pancreatic cancer who have not yet undergone other treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that NP137 is likely to be safe for humans?

Research has shown that NP137, the drug tested in this study, has potential based on early lab studies. These studies suggest that NP137 can effectively work with chemotherapy to combat cancer. Regarding safety, research indicates that NP137 can block a protein involved in cancer spread without causing serious side effects. In other trials, patients took NP137 without major issues.

Although NP137 remains under study, this trial is in its early stages, so information on its long-term safety in humans is limited. However, testing NP137 in people suggests that early safety tests have been encouraging. The trial aims to determine how well NP137 works and how safe it is when used with surgery and chemotherapy for pancreatic cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pancreatic cancer?

Researchers are excited about NP137 because it offers a novel approach to treating pancreatic cancer. Unlike conventional treatments that mainly focus on killing cancer cells, NP137 specifically targets a protein called netrin-1, which plays a crucial role in cancer cell survival and spread. By inhibiting netrin-1, NP137 could potentially prevent the cancer from growing and spreading, offering a new line of attack against this aggressive disease. This unique mechanism of action sets it apart from standard chemotherapy options like FOLFIRINOX, which work by disrupting the DNA of rapidly dividing cells.

What evidence suggests that NP137 might be an effective treatment for pancreatic cancer?

In this trial, participants will receive NP137 combined with the standard-of-care chemotherapy regimen FOLFIRINOX. Research has shown that NP137, when used with chemotherapy like FOLFIRINOX, can improve outcomes for people with pancreatic cancer. Studies have found that NP137 reduces cancer's resistance to chemotherapy, potentially leading to better tumor shrinkage. In past cases, patients with advanced pancreatic cancer lived an average of 12.7 months with this treatment combination. Importantly, NP137 has proven safe and generally does not cause serious side effects. These findings suggest that NP137 could be a promising addition to current pancreatic cancer treatments. ^{1 2 3 6 7}

Who Is on the Research Team?

Aram Hezel

Principal Investigator

University of Rochester

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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 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]

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]

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e16441

LAPNet1: Phase 1b study investigating the association of ... Locally advanced pancreatic ductal adenocarcinoma (LAP) represents 30-40% of cases at the diagnosis, with an overall survival around 15 months.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11002406/

Targeting of netrin-1 by monoclonal antibody NP137 ... 1 More importantly, NP137 has been shown to be safe, with no significant adverse effects in patients with EC. In addition, in a preclinical ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05546853

NCT05546853 | Study Investigating the Association of ... The study drug which is tested is the NP137 in association with mFOLFIRINOX to allow a better tumor response as well as better survival outcomes with an ...

4. withpower.com withpower.com/trial/phase-1-pancreatic-neoplasms-6-2024-18175

NP137 + FOLFIRINOX for Pancreatic Cancer 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 ...

5. pharmatimes.com pharmatimes.com/news/netris_pancreatic_cancer_study_doses_first_patient_1490278/

Netris pancreatic cancer study doses first patient When combined with chemotherapies, NP137 has also been shown to alleviate the cancer's resistance to these conventional treatments.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06203821

NCT06203821 | Study of Perioperative NP137 and ... The aim of this study is to evaluate the mechanism of action for a novel anti-Netrin-1 antibody (NP137) in patients with pancreatic ductal adenocarcinoma.

7. netrispharma.com netrispharma.com/actualites/netris-pharma-doses-first-patient-in-pancreatic-cancer-clinical-study-with-np137/

NETRIS Pharma Doses First Patient in Pancreatic Cancer ... Preclinical studies show NP137 to have an anti-cancer effect as a monotherapy as well as synergistic effects in combination with chemotherapy or ...