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

Study Overview

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

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.

N/A

Metastatic Adenocarcinoma of the Pancreas

DRUG: Irinotecan Liposomal Injection
DRUG: Oxaliplatin
DRUG: 5Fluorouracil
DRUG: Leucovorin
DRUG: Nab-paclitaxel
DRUG: Gemcitabine

D-US-60010-001
2018-003585-14 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2019-09-06	Results First Submitted 2024-02-15	Last Update Submitted that met QC Criteria 2025-02-26
First Submitted that Met QC Criteria 2019-09-06	Results First Submitted that Met QC Criteria 2024-02-15	Last Update Posted (ACTUAL) 2025-02-27
First Posted (ACTUAL) 2019-09-10	Results First Posted 2024-03-13	Last Verified 2025-02

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Irinotecan liposome injection + Oxaliplatin + 5-FU/LV 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).	DRUG: Irinotecan Liposomal Injection Irinotecan liposome injection is irinotecan in the form of the sucrosofate salt, encapsulated in liposomes for i.v. infusion. It is supplied in sterile, single-use vials containing 10 mL of irinotecan liposome injection at a concentration of 4.3 mg/mL fre DRUG: Oxaliplatin Oxaliplatin injection, USP is supplied in single-dose vials containing 50 mg, 100 mg or 200 mg of oxaliplatin as a sterile, preservative-free, aqueous solution at a concentration of 5 mg/mL. DRUG: 5Fluorouracil Fluorouracil injection, USP is a colorless to faint yellow, aqueous, sterile, nonpyrogenic injectable solution available in 50 mL and 100 mL pharmacy bulk package. Each mL contains 50 mg fluorouracil in water for injection, USP. DRUG: Leucovorin Leucovorin Calcium for Injection is supplied in vials ranging from 50-500 mg and available as an injectable solution or lyophilized powder for reconstitution.
ACTIVE_COMPARATOR: Nab-paclitaxel + Gemcitabine Nab-paclitaxel and gemcitabine will be administered on Days 1, 8 and 15 of each 28-day cycle (until progression or unacceptable toxicity).	DRUG: Nab-paclitaxel Nab-paclitaxel is a lyophilised powder containing 100 or 250 mg of paclitaxel formulated as albumin-bound particles in single-use vials for re-constitution. Each mL of the reconstituted formulation will contain 5 mg/mL paclitaxel. DRUG: Gemcitabine Gemcitabine for injection is a lyophilised powder for solution for infusion, with each single use vial containing 200 mg, 1 g or 2 g of gemcitabine.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Irinotecan liposome injection + Oxaliplatin + 5-FU/LV

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).

DRUG: Irinotecan Liposomal Injection

Irinotecan liposome injection is irinotecan in the form of the sucrosofate salt, encapsulated in liposomes for i.v. infusion. It is supplied in sterile, single-use vials containing 10 mL of irinotecan liposome injection at a concentration of 4.3 mg/mL fre

DRUG: Oxaliplatin

Oxaliplatin injection, USP is supplied in single-dose vials containing 50 mg, 100 mg or 200 mg of oxaliplatin as a sterile, preservative-free, aqueous solution at a concentration of 5 mg/mL.

DRUG: 5Fluorouracil

Fluorouracil injection, USP is a colorless to faint yellow, aqueous, sterile, nonpyrogenic injectable solution available in 50 mL and 100 mL pharmacy bulk package. Each mL contains 50 mg fluorouracil in water for injection, USP.

DRUG: Leucovorin

Leucovorin Calcium for Injection is supplied in vials ranging from 50-500 mg and available as an injectable solution or lyophilized powder for reconstitution.

ACTIVE_COMPARATOR: Nab-paclitaxel + Gemcitabine

Nab-paclitaxel and gemcitabine will be administered on Days 1, 8 and 15 of each 28-day cycle (until progression or unacceptable toxicity).

DRUG: Nab-paclitaxel

Nab-paclitaxel is a lyophilised powder containing 100 or 250 mg of paclitaxel formulated as albumin-bound particles in single-use vials for re-constitution. Each mL of the reconstituted formulation will contain 5 mg/mL paclitaxel.

DRUG: Gemcitabine

Gemcitabine for injection is a lyophilised powder for solution for infusion, with each single use vial containing 200 mg, 1 g or 2 g of gemcitabine.

Primary Outcome Measures	Measure Description	Time Frame
Overall Survival (OS)	The OS was defined as time from the date of randomization to the date of death due to any cause. Participants who did not have a date of death recorded at the time of the final analysis were censored at the last known time that the participant was alive. The median OS was measured using Kaplan-Meier technique.	Assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, end of treatment (EoT) visit, then every 2 months thereafter up to DCO date of 23 July 2022 (maximum of 893 days)

Secondary Outcome Measures	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS was defined as the time from the date of randomization to the first documented disease progression using response evaluation criteria in solid tumors (RECIST) Version 1.1 as per Investigator assessment or death due to any cause. The median PFS was measured using Kaplan-Meier technique.	Assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose until EoT visit (maximum of 893 days)
Overall Response Rate (ORR)	The ORR was defined as the percentage of participants with a best overall response (BOR) characterized as either a complete response (CR) or partial response (PR) per RECIST Version 1.1. BOR was defined as the best response as recorded from randomization until documented objective disease progression using RECIST Version 1.1. As per RECIST version 1.1, CR is disappearance of all target lesions; PR is >=30% decrease in the sum of the longest diameter of target lesions; and overall response = CR + PR. The ORR was calculated using Clopper-Pearson method.	Assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose until EoT visit, (maximum of 893 days)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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 ).

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Ipsen Medical Director, Ipsen

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Wainberg ZA, Melisi D, Macarulla T, Pazo Cid R, Chandana SR, De La Fouchardiere C, Dean A, Kiss I, Lee WJ, Goetze TO, Van Cutsem E, Paulson AS, Bekaii-Saab T, Pant S, Hubner RA, Xiao Z, Chen H, Benzaghou F, O'Reilly EM. NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. Lancet. 2023 Oct 7;402(10409):1272-1281. doi: 10.1016/S0140-6736(23)01366-1. Epub 2023 Sep 11.

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