A Study to Assess the Effectiveness and Safety of Irinotecan Liposome Injection, 5-fluorouracil/Leucovorin Plus Oxaliplatin in Patients Not Previously Treated for Metastatic Pancreatic Cancer, Compared to Nab-paclitaxel+Gemcitabine Treatment (NAPOLI 3)

Ipsen

Status and phase

Active, not recruiting

Phase 3

Conditions

Metastatic Adenocarcinoma of the Pancreas

Treatments

Drug: Leucovorin

Drug: Gemcitabine

Drug: Nab-paclitaxel

Drug: 5Fluorouracil

Drug: Oxaliplatin

Drug: Irinotecan Liposomal Injection

Study type

Interventional

Funder types

Industry

Identifiers

NCT04083235

2018-003585-14 (EudraCT Number)

D-US-60010-001

Details and patient eligibility

About

The purpose of this study is to look at the efficacy and safety of Irinotecan liposome injection in combination with other approved drugs used for cancer therapy, namely 5 fluorouracil/leucovorin (5FU/LV) plus oxaliplatin compared to nab-paclitaxel + gemcitabine treatment in improving the overall survival of patients not previously treated for metastatic pancreatic cancer.

Enrollment

770 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Histological or cytologically confirmed adenocarcinoma of the pancreas that has not been previously treated in the metastatic setting.
Initial diagnosis of metastatic disease must have occurred ≤6 weeks prior to screening.
Subject has one or more metastatic lesions measurable by computed tomography (CT) scan (or magnetic resonance imaging (MRI), if the subject is allergic to CT contrast media) according to RECIST Version 1.1 criteria.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Subject has adequate biological parameters as demonstrated by the following blood counts:(a) Absolute neutrophil count (ANC) ≥2000/mm3 without the use of hemopoietic growth factors within the last 7 days prior to randomisation (b) Platelet count ≥100,000/mm3 (c) Haemoglobin (Hgb) ≥9 g/dL obtained ≤14 days prior to randomisation.
Adequate hepatic function as evidenced by: (a) Serum total bilirubin ≤1.5x ULN (biliary drainage is allowed for biliary obstruction), and (b) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5x upper limit of normal (ULN) (≤5x ULN is acceptable if liver metastases are present).
Adequate renal function as evidenced by creatinine clearance ≥30 mL/min.
Adequate coagulation studies (obtained ≤14 days prior to randomisation) as demonstrated by prothrombin time and partial thromboplastin time within normal limits (≤1.5xULN ).

Exclusion criteria

Prior treatment of pancreatic cancer in the metastatic setting with surgery, radiotherapy, chemotherapy or investigational therapy
Prior treatment of pancreatic adenocarcinoma with chemotherapy in the adjuvant setting, except those where at least 12 months have elapsed since completion of the last dose and no persistent treatment-related toxicities are present.
Subject has only localised advanced disease.
Documented serum albumin <3 g/dL
Known history of central nervous system (CNS) metastases.
Clinically significant gastrointestinal disorder
History of any second malignancy in the last 2 years
Concurrent illnesses that would be a relative contraindication to trial participation
Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1
Neuroendocrine (carcinoid, islet cell) or acinar pancreatic carcinoma
Known low or absent dihydropyrimidine dehydrogenase (DPD) activity

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

770 participants in 2 patient groups

Irinotecan liposome injection + Oxaliplatin + 5-FU/LV

Experimental group

Description:

Irinotecan liposome injection, oxaliplatin, 5 FU/LV, will be administered on Days 1 and 15 of each 28-day cycle (until progression or unacceptable toxicity).

Treatment: