Study Investigating the Association of NP137 With mFOLFIRINOX in Locally Advanced Pancreatic Ductal Adenocarcinoma (LAP-NET1)

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.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Drug: NP137; Drug: Oxaliplatin; Drug: Irinotecan; Drug: Calcium levofolinate; Drug: 5 FU

Detailed Description

The study is a multicentric, prospective, single arm phase 1b trial. This study will enroll 43 to 52 patients and consists of 2 parts: Safety Lead-in Phase and Expansion Phase. Initially, 3 to 12 patients will be enrolled into a Safety Lead-in Phase based on a 3 + 3 design, with the possibility of dose de-escalation, to confirm the recommended dose of NP137.The Expansion Phase will start after completion of Safety Lead-in Phase at the confirmed dose and will include 40 patients. Patients will be assigned to the experimental arm (NP137 + mFOLFIRINOX).

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Anna BOROWIK; Phone Number: 0476769314; Email: aborowik@chu-grenoble.fr
• Study Contact Backup: Name: Laure Bordy; Phone Number: 0476766150; Email: LBordy@chu-grenoble.fr

Study Locations

• France
  • Bordeaux, France, 33404
    • Recruiting
    • CHU de Bordeaux
    • Contact: Jean Fredéric BLANC
  • Lille, France, 59037
    • Recruiting
    • CHRU Lille
    • Contact: Anthony TURPIN
  • Lyon, France, 69008
    • Recruiting
    • Hopital Prive Jean Mermoz
    • Contact: Pascal ARTRU
  • Paris, France, 75013
    • Recruiting
    • AP-HP Pitié Salpetrière
    • Contact: Jean-Baptiste BACHET
  • Poitiers, France, 86000
    • Recruiting
    • CHU Poitiers
    • Contact: Camille EVRARD
  • Reims, France, 51092
    • Recruiting
    • CHU de Reims
    • Contact: Olivier BOUCHE
  • Rennes, France, 35033
    • Recruiting
    • CHU Rennes
    • Contact: Astrid LIEVRE
  • Saint-Étienne, France, 42055
    • Recruiting
    • CHU St Etienne
    • Contact: Nicolas WILLIET
  • Alpes
    • Grenoble, Alpes, France, 38043
      • Recruiting
      • CHU de Grenoble Alpes
      • Contact: Gaël ROTH; Phone Number: Groth@chu-grenoble.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age from 18 to 79 years
2. Able to understand and sign informed consent
3. Histologically or cytologically proven diagnosis of pancreatic ductal adenocarcinoma
4. Locally advanced pancreatic cancer considered unresectable according to NCCN Guidelines® Version 2.2021
5. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors RECIST 1.1 criteria
6. Male, or non-pregnant and non-lactating female
7. 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
8. 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
9. No prior systemic therapy, radiation therapy, or resection for pancreatic cancer
10. Life expectancy ≥ 12 weeks
11. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

12. Adequate liver function:

    1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x upper limit of normal (ULN),
    2. Bilirubin ≤ 1.5 x ULN or in subjects with biliary stenting ≤ 2.0 x ULN
    3. Alkaline phosphatase < 2.5 x ULN
    4. Subjects with biliary stenting do not need to wait for their alkaline phosphatase to become < 2.5 x ULN if their total bilirubin, AST and ALT have improved to within required study levels with criteria 12a and 12b
13. Adequate bone marrow function: platelets >100,000 cells/mm3, hemoglobin > 9.0 g/dl and absolute neutrophil count (ANC) >1,500 cells/mm3
14. Adequate renal function: creatinine < 1.5 x ULN, creatinine clearance ≥ 30 mL/min/m2
15. Adequate nutritional state with Albumin ≥ 2.5 g/dL
16. Less than grade 2 pre-existing peripheral neuropathy (per CTCAE)
17. Patients covered by Health Insurance System

Exclusion Criteria:

1. Patients with resectable pancreatic cancer
2. Evidence of the presence of metastases.
3. Patients who have received prior systemic therapy, radiation therapy, or resection for pancreatic cancer or prior therapy with NP137
4. Patients with known Dihydropyrimidine dehydrogenase (DPD) deficiency, or homozygosity for UGT1A1*28 polymorphism (UGT1A1 genotype analysis is not required to be eligible)
5. Previous (within the past 3 years) or concurrent malignancy diagnosis except non-melanoma skin cancer and in situ carcinomas (excluding in situ breast cancer)
6. History of severe (grade ≥ 3) allergic reactions to one of the components of chemotherapy, or NP137
7. 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
8. 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
9. Major surgery within 4 weeks prior to signing informed consent form. Biliary stents are permitted
10. History of allergy or hypersensitivity to human, humanized or chimeric monoclonal antibodies
11. History of allergy or hypersensitivity to any of the chemotherapy agents belonging to mFOLFIRINOX regimen
12. Subjects with a history of chronic HCV, HBV or HIV infection
13. Subjects who have been administered a live vaccine within four weeks prior to the first administration of therapy
14. Subjects who cannot stop chronic medications that inhibit or induce CYP2C8 or CYP3A4
15. 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)
16. Patients who have active infection requiring systemic therapy (other than HCV, HBV, HIV).
17. Patients who participate or plan to participate in another interventional clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental; NP137+ mFOLFIRINOX

Drug: NP137; 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.; Drug: Oxaliplatin; Oxaliplatin will be administreted at the first day of each cycle (CnD1) of 14 days as an IV infusion at 85 mg/m²; Drug: Irinotecan; Irinotecan will be administreted at the first day of each cycle (CnD1) of 14 days as an IV infusion at 150 mg/m²; Drug: Calcium levofolinate; Calcium levofolinate will be administreted at the first day of each cycle (CnD1) of 14 days as an IV infusion at 100 mg/m²; Drug: 5 FU; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best overall objective response rate (ORR)	Best overall objective response rate (ORR) according to RECIST 1.1	At 2,4 and 6 months
Overall survival (OS)	Median Overall survival (OS) and 12 months-OS rates. OS is defined as the time between inclusion and death (all causes). Patients alive will be censored at the date of last news.	at 12 and 36 months
Progression-Free Survival (PFS)	Median Progression-Free Survival (PFS) and 12 months-PFS rates. PFS is defined as the time between inclusion and progression according to RECIST 1.1 or death (all causes). Patients alive without progression will be censored at the date of last news.	at 12 and 36 months
Median Duration of response	Median Duration of response is defined as the time between first dose of treatment and progression according to RECIST 1.1. Patients alive without progression will be censored at the date of last news.	at 36 months
Quality of life (QoL)	Quality of life will be studied by using the EORTC QLQ-C30 questionnaire (European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire for Cancer). A 5-point decrease of QLQ-C30 score will be considered as the minimal clinically significant deterioration of QoL.	at 36 months
time to deterioration	TTD will be defined as the time from inclusion in the study to deterioration of EORTC QLQ-C30 score with a decrease ≥5 points at any time point after the baseline score.	at 36 months
PK-PD evaluation	PK-PD evaluation: based on available PopPK modelisation and PK samples collected at the time of the response evaluation in this study	at 36 months
proportion of patients reaching surgery	Percentage surgical resection with R0/R1 margins	at 36 months

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble
• Collaborators: NETRIS Pharma
• Investigators: Principal Investigator: Gaël ROTH, MD PHD, University Hospital, Grenoble

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2023
• Primary Completion (Estimated): November 28, 2024
• Study Completion (Estimated): November 28, 2025

Study Registration Dates

• First Submitted: September 15, 2022
• First Submitted That Met QC Criteria: September 15, 2022
• First Posted (Actual): September 21, 2022

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Oxaliplatin; Leucovorin; Irinotecan; Calcium; Levoleucovorin
• Other Study ID Numbers: 38RC22.0211

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No