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.
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
43
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 will be administreted at the first day of each cycle (CnD1) of 14 days as an IV infusion at 85 mg/m²
Irinotecan will be administreted at the first day of each cycle (CnD1) of 14 days as an IV infusion at 150 mg/m²
CHU de GRENOBLE ALPES
Grenoble, Alpes, France
CHU de BORDEAUX
Bordeaux, France
CHRU Lille
Lille, France
Hôpital Privé Jean Mermoz
Lyon, France
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.
Time frame: At 6 months
Best overall objective response rate (ORR)
Best overall objective response rate (ORR) and ORR at 3 months, 6, 9, 12 months according to RECIST 1.1
Time frame: At 3,6,9 and 12 months
Overall survival (OS)
Median Overall survival (OS), 6 months 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.
Time frame: at 6, 12 and 36 months
Progression-Free Survival (PFS)
Median Progression-Free Survival (PFS), 6 months 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.
Time frame: at 6, 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 6 months and at the date of last news.
Time frame: at 6 and 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) at 6 months and at the end of study. A 5-point decrease of QLQ-C30 score will be considered as the minimal clinically significant deterioration of QoL.
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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 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.
AP-HP Pitié Salpetrière
Paris, France
CHU Poitiers
Poitiers, France
CHU de REIMS
Reims, France
CHU Rennes
Rennes, France
CHU St Etienne
Saint-Etienne, France
Time frame: at 6 and 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 6 months and at the end of study
Time frame: at 6 and 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
Time frame: at 36 months
CA19.9 response
CA19.9 response will be defined as a percentage of patients with a ≥ 50% reduction from baseline CA19.9 level, at 6 and 12 months.
Time frame: at 6 and 12 months
proportion of patients reaching surgery
Percentage surgical resection with R0/R1 margins at 6 months and at the end of study.
Time frame: at 6 and 36 months
Mechanisms of EMT
To assess the mechanisms of EMT reversal by comparing different histological markers on pre-therapeutic biopsies with tumor samples obtained during surgical tumor resection. Descriptive study in spatial transcriptomics and immunohistochemistry of the evolution of EMT markers, Netrin-1 expression, and tumor microenvironment by comparing pre-therapeutic biopsies to tumor samples obtained during surgical tumor resection
Time frame: At month 0