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

Metastatic Adenocarcinoma of the Pancreas Clinical Trial

— NAPOLI 3  

Official title:

An Open-label, Randomised, Multicentre, Phase III Study of Irinotecan Liposome Injection, Oxaliplatin, 5-fluorouracil/Leucovorin Versus Nab-paclitaxel Plus Gemcitabine in Subjects Who Have Not Previously Received Chemotherapy for Metastatic Adenocarcinoma of the Pancreas

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04083235
• Other study ID #: D-US-60010-001
• Secondary ID: 2018-003585-14
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 11, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2024
• Source: Ipsen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 770
• Est. completion date: December 31, 2024
• Est. primary completion date: July 23, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Metastatic Adenocarcinoma of the Pancreas

Intervention

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 free base equivalent (FBE).
• 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.
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Australia	Bankstown-Lidcombe Hospital	Bankstown
Australia	Monash Medical Centre	Clayton
Australia	Fiona Stanley Hospital	Murdoch
Australia	Sir Charles Gairdner Hospital	Nedlands
Australia	St John of God Subiaco Hospital	Subiaco
Australia	Queen Elizabeth Hospital	Woodville South
Austria	Medizinische Universitaet Graz	Graz
Austria	Ordensklinikum Linz GmbH Barmherzige Schwestern	Linz
Austria	SCRI-CCCIT Gemeinnutzige Gmbh- Gemeinnutzige Salzburger Landeskliniken Betriebsgesmbh	Salzburg
Austria	Medical University of Vienna	Vienna
Belgium	Onze-Lieve-Vrouwziekenhuis	Aalst
Belgium	ASBL Grand Hôpital de Charleroi (GHdC), Site Notre Dame	Charleroi
Belgium	Universitair Ziekenhuis Antwerpen (UZA)	Edegem
Belgium	University Hospital Gent	Gent
Belgium	Hospital centre Jolimont	Haine-Saint-Paul
Belgium	University Hospital (UZ) Leuven	Leuven
Belgium	University Hospital Mont-Godinne	Yvoir
Brazil	Fundação Pio XII - Hospital de Câncer de Barretos	Barretos
Brazil	Centro Regional Integrado de Oncologia (CRIO)	Ceara
Brazil	Instituto de Oncologia do Parana - IOP	Curitiba
Brazil	Centro de Pesquisas Oncológicas - CEPON	Florianópolis
Brazil	Hospital de Caridade de Ijui	Ijuí
Brazil	Clinica Neoplasias Litoral	Itajaí
Brazil	Hospital Bruno Born	Lajeado
Brazil	Centro de Pesquisas Clinicas de Natal - CPCLIN	Natal
Brazil	Irmandade da Santa Casa de Misericordia de Porto Alegre	Porto Alegre
Brazil	Instituto COI	Rio De Janeiro
Brazil	Instituto Nacional Do Cancer (INCA)	Rio de Janeiro
Brazil	Instituto Brasileiro de Controle do Cancer - IBCC (Sao Paulo)	San Paolo
Brazil	CIP Centro Integrado de Pesquisas do Hospital de Base	São José Do Rio Preto
Brazil	Hospital Alemão Oswaldo Cruz	São Paulo
Brazil	Instituto do Cancer do Estado de São Paulo (ICESP)	São Paulo
Canada	Alberta Health Services Cross Cancer Institute	Edmonton
Canada	Queen Elizabeth II Health Sciences Centre	Halifax
Canada	McGill University Faculty of Medicine - Royal Victoria Hospital	Montréal
Canada	Centre Hospitalier Universitaire de Sherbrooke	Sherbrooke
Czechia	Masarykuv onkologicky ustav	Brno
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Králové
Czechia	University Hospital Olomouc, Department of Oncology	Olomouc
Czechia	Thomayerova Nemocnice	Praha
France	CHRU de Tours - Hôpital Trousseau	Chambray-lès-Tours
France	Centre Oscar Lambret	Lille
France	Centre Leon Berard	Lyon
France	Hôpital Edouard Herriot	Lyon
France	Hopital Prive Jean Mermoz	Lyon
France	Centre Antoine-Lacassagne	Nice
France	Hopital Saint Louis	Paris
France	CHU Bordeaux - Hopital Haut-Leveque	Pessac
France	Centre Hospitalier Universitaire de Poitiers - Poitiers University Hospital	Poitiers Cedex
France	Strasbourg Oncologie Liberale	Strasbourg
Germany	Charité - Universitaetsmedizin Berlin	Berlin
Germany	St. Josef-Hospital	Bochum
Germany	Klinikum Esslingen GmbH	Esslingen
Germany	Krankenhaus Nordwest	Frankfurt
Germany	Martin Luther Universitat Halle-Wittenberg	Halle
Germany	Studiengesellschaft BSF	Halle
Germany	Asklepios Klinik Altona	Hamburg
Germany	Facharztzentrum Eppendorf	Hamburg
Germany	Marienkrankenhaus Hamburg	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Slk-Kliniken	Heilbronn
Germany	Klinikum Mannheim	Mannheim
Germany	Krankenhaus St. Franziskus - Kliniken Maria Hilf GmbH	Mönchengladbach
Germany	Universitaetsklinikum Tuebingen	Tuebingen
Germany	Universitaetsklinikum Ulm	Ulm
Greece	Agios Savvas Anticancer Hospital	Athens
Greece	General Hospital of Athens - Laiko	Athens
Greece	National and Kapodistrian University of Athens	Athens
Greece	University General Hospital of Ioannina	Ioánnina
Greece	Theagenion Hospital	Thessaloníki
Hungary	Dél-pesti Centrumkórház - Szent László Kórház telephely	Budapest
Hungary	Országos Onkológiai Intézet	Budapest
Hungary	Semmelweis Egyetem Belgyógyászati és Hematológiai Klinika	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen
Hungary	Somogy Megyei Kaposi Mor Oktato Korhaz	Kaposvár
Hungary	Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Rendelointézet	Szolnok
Israel	Soroka Medical Center	Beer Sheva
Israel	Rambam Health Care Campus	Haifa
Italy	Policlinico S. Orsola-Malpighi	Bologna
Italy	Istituto Romagnolo per lo Studio dei Tumori Dino Amadori	Meldola
Italy	Istituto Europeo di Oncologia	Milano
Italy	Azienda Ospedaliero-Universitaria di Modena	Modena
Italy	AUSL di Piacenza-Ospedale Guglielmo Da Saliceto	Piacenza
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	AOU Ospedali Riuniti di Ancona	Torrette
Italy	Azienda Ospedaliera - Universitaria Integrata di Verona - Ospedale Borgo Roma	Verona
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	CHA Bundang Medical Center	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Seoul St. Mary's Hospital, The Catholic University of Korea	Seoul
Portugal	Hospital de Braga	Braga
Portugal	Centro Hospitalar Universitario de Lisboa Norte - Hospital de Santa Maria	Lisboa
Portugal	Champalimaud Cancer Center	Lisbon
Portugal	Unidade Local de Saude Matosinhos E.P.E. Hospital Pedro Hispano	Senhora da Hora
Portugal	Centro Hospitalar de Vila Nova de Gaia/Espinho EPE	Vila Nova de Gaia
Russian Federation	Evimed LLC	Chelyabinsk
Russian Federation	Limited Liability Company- Clinica Druzhkovyh	Kazan
Russian Federation	Kursk Regional Clinical Oncology Dispensary	Kursk
Russian Federation	Main Military Clinical Hospital named after N.N. Burdenko	Moscow
Russian Federation	Volga District Medical Centre	Novgorod
Russian Federation	Federal State Budgetary Institution - Russian Scientific Center of Radiology and Surgical Technologies n.a. academician A.M.Granov	Saint-Petersburg
Spain	Hospital General Universitario de Elche	Alicante
Spain	Hospital Universitario de Badajoz	Badajoz
Spain	Hospital Germans Trias i Pujol	Badalona
Spain	Corporacio Sanitaria Parc Tauli - Hospital de Sabadell	Barcelona
Spain	Hospital Clinic Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau Barcelona	Barcelona
Spain	Hospital Quironsalud Barcelona	Barcelona
Spain	Hospital Vall D Hebron	Barcelona
Spain	Institut Catala d'Oncologia - L'Hospitalet	Barcelona
Spain	Complejo Hospitalario Universitario de Granada - Hospital Universitario Virgen de las Nieves	Granada
Spain	Centro Integral Oncologico Clara Campal	Madrid
Spain	Fundacion Jimenez Diaz	Madrid
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Regional Universitario de Malaga	Málaga
Spain	Complejo Hospitalario de Navarra	Pamplona
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Hospital Universitario Miguel Servet	Zaragoza
United Kingdom	Guy's and St. Thomas' NHS Foundation Trust	London
United Kingdom	Imperial College Healthcare NHS Trust	London
United Kingdom	Royal Marsden Foundation Trust	London
United Kingdom	Royal Marsden Foundation Trust	London
United Kingdom	Cancer Research UK - Christie Hospital Foundation NHS Trust - Dept of Medical Oncology	Manchester
United Kingdom	Nottingham City Hospital	Nottingham
United States	Messino Cancer Center	Asheville	North Carolina
United States	Texas Oncology - Austin	Austin	Texas
United States	Comprehensive Blood And Cancer Center	Bakersfield	California
United States	Hematology Oncology Clinic	Baton Rouge	Louisiana
United States	Frontier Cancer Center	Billings	Montana
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess	Boston	Massachusetts
United States	Chattanooga Oncology Hematology Care - Tennessee Oncology	Chattanooga	Tennessee
United States	Rush University Medical Center	Chicago	Illinois
United States	UC Health Memorial Hospital	Colorado Springs	Colorado
United States	The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solovev Research Institute (OSUCCC - James)	Columbus	Ohio
United States	University of California- Irvine Health Cancer Cente	Costa Mesa	California
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	City of Hope National Medical Center	Duarte	California
United States	Edward Hospital - Elmhurst	Elmhurst	Illinois
United States	Oncology Associates of Oregon	Eugene	Oregon
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana
United States	The Center for Cancer and Blood Disorders	Fort Worth	Texas
United States	Banner Health- MD Anderson Cancer Center	Gilbert	Arizona
United States	Cancer and Hematology Centers of Western Michigan	Grand Rapids	Michigan
United States	Greenville Hospital System	Greenville	South Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	Houston Methodist Research Institute	Houston	Texas
United States	MD Anderson Cancer Center	Houston	Texas
United States	Oncology Consultants	Houston	Texas
United States	Research Medical Center	Kansas City	Missouri
United States	Clinical Research Alliance, Inc	Lake Success	New York
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	University of Kentucky Markey Cancer Center	Lexington	Kentucky
United States	University of California, Los Angeles (UCLA)	Los Angeles	California
United States	The West Cancer Center	Memphis	Tennessee
United States	Miami Cancer Institute	Miami	Florida
United States	Mount Sinai Medical Center of Florida, Inc.	Miami Beach	Florida
United States	Froedtert Hospital and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Health Partners Institute	Minneapolis	Minnesota
United States	Sarah Cannon and HCA Research Institute	Nashville	Tennessee
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Oklahoma - Health Sciences Center	Oklahoma City	Oklahoma
United States	Oncology Hematology West P.C. dba Nebraska Cancer Specialists	Omaha	Nebraska
United States	St. Jude Hospital Yorba Linda dba St. Joseph Heritage Healthcare	Orange	California
United States	University of California - Irvine Medical Center	Orange	California
United States	Illinois CancerCare - Peoria	Peoria	Illinois
United States	Mayo Clinic - Scottsdale	Phoenix	Arizona
United States	Pikeville Medical Center	Pikeville	Kentucky
United States	University of Pittsburgh Medical Center (UPMC) - Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Compass Oncology - Rose Quarter Cancer Center	Portland	Oregon
United States	Kaiser Permanente - Northwest	Portland	Oregon
United States	Oregon Health & Science University (OHSU)	Portland	Oregon
United States	Torrance Memorial Physician Network Cancer Care	Redondo Beach	California
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Sutter Health Sacramento	Sacramento	California
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	Florida Cancer Specialists - Fort Myers	Sarasota	Florida
United States	Maine Center for Cancer Medicine	Scarborough	Maine
United States	Willis-Knighton Cancer Center	Shreveport	Louisiana
United States	Maryland Oncology Hematology	Silver Spring	Maryland
United States	Siouxland Hematology - Oncology Associates, LLP	Sioux City	Iowa
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Florida Cancer Specialists - Panhandle	Tallahassee	Florida
United States	Florida Cancer Specialists - St. Petersburg	Tampa	Florida
United States	Toledo Clinic Cancer Center	Toledo	Ohio
United States	Texas Oncology - Tyler	Tyler	Texas
United States	Carle Cancer Center	Urbana	Illinois
United States	Florida Cancer Specialists - East	West Palm Beach	Florida
United States	Presbyterian Intercommunity Hospital (PIH)	Whittier	California
United States	Texas Oncology - Wichita Falls	Wichita Falls	Texas
United States	Blue Ridge Cancer Care	Wytheville	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Ipsen

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Czechia,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Korea, Republic of,  Portugal,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)