Study Investigating the Association of NP137 With mFOLFIRINOX in Locally Advanced Pancreatic Ductal Adenocarcinoma

NCT05546853 | Completed Phase 1 DMC

• 1 other identifier: 38RC22.0211
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 9

Brief Summary

The study will assess the safety of the association of NP137 with the standard of care mFOLFIRINOX in the treatment of locally advanced pancreatic ductal adenocarcinoma.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 acceptable safety.

Conditions

Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Percentage Proportion of patients experiencing adverse events

  Percentage Proportion of patients experiencing adverse events (AEs) of any grade and grade 3/4 AEs as defined by the National Cancer Institute - Common Terminology Criteria for Adverse Events (CTCAE v 5.0) at 6 months.

  At 6 months

Secondary Outcomes (10)

• Best overall objective response rate (ORR)

  At 3,6,9 and 12 months

• Overall survival (OS)

  at 6, 12 and 36 months

• Progression-Free Survival (PFS)

  at 6, 12 and 36 months

• Median Duration of response

  at 6 and 36 months

• Quality of life (QoL)

  at 6 and 36 months

Study Arms (1)

Experimental

EXPERIMENTAL

NP137+ mFOLFIRINOX

Drug: NP137; Drug: Oxaliplatin; Drug: Irinotecan; Drug: Calcium levofolinate; Drug: 5 FU

Interventions

NP137 DRUG

NP137 will be administrated at the first day of each cycle (CnD1) of 14 days as an IV infusion at 9 or 14 mg/kg.

Experimental

Oxaliplatin DRUG

Oxaliplatin will be administreted at the first day of each cycle (CnD1) of 14 days as an IV infusion at 85 mg/m²

Experimental

Irinotecan DRUG

Irinotecan will be administreted at the first day of each cycle (CnD1) of 14 days as an IV infusion at 150 mg/m²

Experimental

Calcium levofolinate DRUG

Calcium levofolinate will be administreted at the first day of each cycle (CnD1) of 14 days as an IV infusion at 100 mg/m²

Experimental

5 FU DRUG

5 FU will be administreted at the first day of each cycle (CnD1) of 14 days as an IV infusion at 2400 mg/m2 as a continuous intravenous infusion over 46 hours.

Experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age from 18 to 79 years
• Able to understand and sign informed consent
• Histologically or cytologically proven diagnosis of pancreatic ductal adenocarcinoma
• Locally advanced pancreatic cancer considered unresectable according to NCCN Guidelines® Version 2.2021
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors RECIST 1.1 criteria
• Male, or non-pregnant and non-lactating female
• Women patients of childbearing potential\* must have a negative serum/urine pregnancy test at screening and baseline, and be willing to use a highly effective\*\* contraception. The patient should be advised to continue the contraception for at least 6 months following the completion of dosing. Women with cessation for \> 24 months of previously occurring menses, or women of any age who have had a hysterectomy, or have had both ovaries removed will be considered to be of non-childbearing potential
• Male patients of reproductive potential must be willing to use one acceptable method of contraception, as judged by Investigator and Sponsor and/or to refrain from donating sperm from the time of screening through at least 6 months following the completion of dose administration
• No prior systemic therapy, radiation therapy, or resection for pancreatic cancer
• Life expectancy ≥ 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate liver function:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5 x upper limit of normal (ULN),
• Bilirubin ≤ 1.5 x ULN or in subjects with biliary stenting ≤ 2.0 x ULN
• Alkaline phosphatase \< 2.5 x ULN

You may not qualify if:

• Patients with resectable pancreatic cancer
• Evidence of the presence of metastases.
• Patients who have received prior systemic therapy, radiation therapy, or resection for pancreatic cancer or prior therapy with NP137
• Patients with known Dihydropyrimidine dehydrogenase (DPD) deficiency, or homozygosity for UGT1A1\*28 polymorphism (UGT1A1 genotype analysis is not required to be eligible)
• Previous (within the past 3 years) or concurrent malignancy diagnosis except non-melanoma skin cancer and in situ carcinomas (excluding in situ breast cancer)
• History of severe (grade ≥ 3) allergic reactions to one of the components of chemotherapy, or NP137
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, may decrease subject's compliance to study's procedures or may render the patient at high risk from treatment complications in the opinion of the treating investigator
• Subjects with known poorly controlled comorbid conditions, including; congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), uncontrolled diabetes mellitus (DM) or neurologic disorders (not acutely related to pancreatic cancer) or limited function
• Major surgery within 4 weeks prior to signing informed consent form. Biliary stents are permitted
• History of allergy or hypersensitivity to human, humanized or chimeric monoclonal antibodies
• History of allergy or hypersensitivity to any of the chemotherapy agents belonging to mFOLFIRINOX regimen
• Subjects with a history of chronic HCV, HBV or HIV infection
• Subjects who have been administered a live vaccine within four weeks prior to the first administration of therapy
• Subjects who cannot stop chronic medications that inhibit or induce CYP2C8 or CYP3A4
• Persons referred to in Articles L1121-5 to L1121-8 of the French code of public health (this corresponds to all persons protected: pregnant or parturient women, breastfeeding mothers, persons deprived of liberty by judicial or administrative decision, persons subject to a legal protection measure)

Sponsors & Collaborators

• NETRIS Pharma: collaborator
• University Hospital, Grenoble: lead

Study Sites (9)

CHU de GRENOBLE ALPES

Grenoble, Alpes, 38043, France

Location

CHU de BORDEAUX

Bordeaux, 33404, France

Location

CHRU Lille

Lille, 59037, France

Location

Hôpital Privé Jean Mermoz

Lyon, 69008, France

Location

AP-HP Pitié Salpetrière

Paris, 75013, France

Location

CHU Poitiers

Poitiers, 86000, France

Location

CHU de REIMS

Reims, 51092, France

Location

CHU Rennes

Rennes, 35033, France

Location

CHU St Etienne

Saint-Etienne, 42055, France

Location

Related Publications (1)

• Roth G, Artru P, Bouche O, Williet N, Ghelfi J, Turpin A, Lievre A, Blanc JF, Evrard C, Bachet JB, Parent P, Manceau M, Roustit M, Borowik A, Granger V, Durand A, d'Engremont C, Girard E, Chirica M, Braissand N, Rama N, Modolo E, Hernandez-Vargas H, Georges E, Scoazec JY, Cros J, Hazard S, Ducarouge B, Decaens T, Bernet A, Mehlen P. Netrin1 blockade alleviates resistance to chemotherapy in pancreatic cancer. Nature. 2026 Apr 22. doi: 10.1038/s41586-026-10436-4. Online ahead of print.

  PMID: 42020751 DERIVED

MeSH Terms

Interventions

netrin-1 inhibitor NP137; Oxaliplatin; Irinotecan

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Gaël ROTH, MD PHD

  University Hospital, Grenoble

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicentric prospective single arm phase 1b trial.

Study Record Dates

• First Submitted: September 15, 2022
• First Posted: September 21, 2022
• Study Start: March 28, 2023
• Primary Completion: December 9, 2024
• Study Completion: June 16, 2025
• Last Updated: May 19, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (9)