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

Pancreatic Ductal Adenocarcinoma Clinical Trial

— LAP-NET1  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05546853
• Other study ID #: 38RC22.0211
• Status: Recruiting
• Phase: Phase 1
• Start date: March 28, 2023
• Est. completion date: November 28, 2025

Study information

• Verified date: December 2023
• Source: University Hospital, Grenoble
• Contact: Anna BOROWIK
• Phone: 0476769314
• Email: aborowik[@]chu-grenoble.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 52
• Est. completion date: November 28, 2025
• Est. primary completion date: November 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Pancreatic Ductal Adenocarcinoma

Intervention

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.
• Oxaliplatin
Oxaliplatin will be administreted at the first day of each cycle (CnD1) of 14 days as an IV infusion at 85 mg/m²
• Irinotecan
Irinotecan will be administreted at the first day of each cycle (CnD1) of 14 days as an IV infusion at 150 mg/m²
• 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
• 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.

Locations

Country	Name	City	State
France	CHU de BORDEAUX	Bordeaux
France	CHU de GRENOBLE ALPES	Grenoble	Alpes
France	CHRU Lille	Lille
France	Hôpital Privé Jean Mermoz	Lyon
France	AP-HP Pitié Salpetrière	Paris
France	CHU Poitiers	Poitiers
France	CHU de REIMS	Reims
France	CHU Rennes	Rennes
France	CHU St Etienne	Saint-Étienne

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Grenoble	NETRIS Pharma

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Best overall objective response rate (ORR)	Best overall objective response rate (ORR) according to RECIST 1.1	At 2,4 and 6 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	proportion of patients reaching surgery	Percentage surgical resection with R0/R1 margins	at 36 months