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

Sponsor

University Hospital, Grenoble (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05546853

Collaborator

NETRIS Pharma (Industry)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Ductal Adenocarcinoma	Drug: NP137 Drug: Oxaliplatin Drug: Irinotecan Drug: Calcium levofolinate Drug: 5 FU	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

52 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Multicentric prospective single arm phase 1b trial.Multicentric prospective single arm phase 1b trial.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Nov 1, 2022

Anticipated Primary Completion Date :

Nov 1, 2024

Anticipated Study Completion Date :

Nov 1, 2024

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Percentage Proportion of patients experiencing adverse events [At 6 months]
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.

Secondary Outcome Measures

Best overall objective response rate (ORR) [At 2,4 and 6 months]
Best overall objective response rate (ORR) according to RECIST 1.1

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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 (Appendix 11)
Measurable disease as defined by Response Evaluation Criteria in Solid Tumors RECIST 1.1 criteria (Appendix 2)
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
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
Adequate bone marrow function: platelets >100,000 cells/mm3, hemoglobin > 9.0 g/dl and absolute neutrophil count (ANC) >1,500 cells/mm3
Adequate renal function: creatinine < 1.5 x ULN, creatinine clearance ≥ 30 mL/min/m2
Adequate nutritional state with Albumin ≥ 2.5 g/dL
Less than grade 2 pre-existing peripheral neuropathy (per CTCAE)
Patients covered by Health Insurance System

Exclusion Criteria:

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
Subject in exclusion period for another study
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).