Trial Review

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04083235




Registration number
NCT04083235
Ethics application status
Date submitted
6/09/2019
Date registered
10/09/2019
Date last updated
1/10/2024

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2018-003585-14
Secondary ID [2] 0 0
D-US-60010-001
Universal Trial Number (UTN)
Trial acronym
NAPOLI 3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Adenocarcinoma of the Pancreas 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Irinotecan Liposomal Injection
Treatment: Drugs - Oxaliplatin
Treatment: Drugs - 5Fluorouracil
Treatment: Drugs - Leucovorin
Treatment: Drugs - Nab-paclitaxel
Treatment: Drugs - Gemcitabine

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).

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).


Treatment: Drugs: 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).

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
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 [1] 0 0
Progression Free Survival (PFS)
Timepoint [1] 0 0
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 outcome [2] 0 0
Overall Response Rate (ORR)
Timepoint [2] 0 0
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)

Eligibility
Key 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 ).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/02/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2024
Actual
Sample size
Target
Accrual to date
Final
770
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Bankstown-Lidcombe Hospital - Bankstown
Recruitment hospital [2] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [3] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [4] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [5] 0 0
St John of God Subiaco Hospital - Subiaco
Recruitment hospital [6] 0 0
Queen Elizabeth Hospital - Woodville South
Recruitment postcode(s) [1] 0 0
2200 - Bankstown
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
6150 - Murdoch
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment postcode(s) [5] 0 0
6008 - Subiaco
Recruitment postcode(s) [6] 0 0
5011 - Woodville South
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Iowa
Country [9] 0 0
United States of America
State/province [9] 0 0
Kentucky
Country [10] 0 0
United States of America
State/province [10] 0 0
Louisiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Maine
Country [12] 0 0
United States of America
State/province [12] 0 0
Maryland
Country [13] 0 0
United States of America
State/province [13] 0 0
Massachusetts
Country [14] 0 0
United States of America
State/province [14] 0 0
Michigan
Country [15] 0 0
United States of America
State/province [15] 0 0
Minnesota
Country [16] 0 0
United States of America
State/province [16] 0 0
Missouri
Country [17] 0 0
United States of America
State/province [17] 0 0
Montana
Country [18] 0 0
United States of America
State/province [18] 0 0
Nebraska
Country [19] 0 0
United States of America
State/province [19] 0 0
Nevada
Country [20] 0 0
United States of America
State/province [20] 0 0
New York
Country [21] 0 0
United States of America
State/province [21] 0 0
North Carolina
Country [22] 0 0
United States of America
State/province [22] 0 0
Ohio
Country [23] 0 0
United States of America
State/province [23] 0 0
Oklahoma
Country [24] 0 0
United States of America
State/province [24] 0 0
Oregon
Country [25] 0 0
United States of America
State/province [25] 0 0
Pennsylvania
Country [26] 0 0
United States of America
State/province [26] 0 0
South Carolina
Country [27] 0 0
United States of America
State/province [27] 0 0
Tennessee
Country [28] 0 0
United States of America
State/province [28] 0 0
Texas
Country [29] 0 0
United States of America
State/province [29] 0 0
Utah
Country [30] 0 0
United States of America
State/province [30] 0 0
Virginia
Country [31] 0 0
United States of America
State/province [31] 0 0
Wisconsin
Country [32] 0 0
Austria
State/province [32] 0 0
Graz
Country [33] 0 0
Austria
State/province [33] 0 0
Linz
Country [34] 0 0
Austria
State/province [34] 0 0
Salzburg
Country [35] 0 0
Austria
State/province [35] 0 0
Vienna
Country [36] 0 0
Belgium
State/province [36] 0 0
Aalst
Country [37] 0 0
Belgium
State/province [37] 0 0
Charleroi
Country [38] 0 0
Belgium
State/province [38] 0 0
Edegem
Country [39] 0 0
Belgium
State/province [39] 0 0
Gent
Country [40] 0 0
Belgium
State/province [40] 0 0
Haine-Saint-Paul
Country [41] 0 0
Belgium
State/province [41] 0 0
Leuven
Country [42] 0 0
Belgium
State/province [42] 0 0
Yvoir
Country [43] 0 0
Brazil
State/province [43] 0 0
Barretos
Country [44] 0 0
Brazil
State/province [44] 0 0
Ceara
Country [45] 0 0
Brazil
State/province [45] 0 0
Curitiba
Country [46] 0 0
Brazil
State/province [46] 0 0
Florianópolis
Country [47] 0 0
Brazil
State/province [47] 0 0
Ijuí
Country [48] 0 0
Brazil
State/province [48] 0 0
Itajaí
Country [49] 0 0
Brazil
State/province [49] 0 0
Lajeado
Country [50] 0 0
Brazil
State/province [50] 0 0
Natal
Country [51] 0 0
Brazil
State/province [51] 0 0
Porto Alegre
Country [52] 0 0
Brazil
State/province [52] 0 0
Rio de Janeiro
Country [53] 0 0
Brazil
State/province [53] 0 0
Rio De Janeiro
Country [54] 0 0
Brazil
State/province [54] 0 0
San Paolo
Country [55] 0 0
Brazil
State/province [55] 0 0
São José Do Rio Preto
Country [56] 0 0
Brazil
State/province [56] 0 0
São Paulo
Country [57] 0 0
Canada
State/province [57] 0 0
Edmonton
Country [58] 0 0
Canada
State/province [58] 0 0
Halifax
Country [59] 0 0
Canada
State/province [59] 0 0
Montréal
Country [60] 0 0
Canada
State/province [60] 0 0
Sherbrooke
Country [61] 0 0
Czechia
State/province [61] 0 0
Brno
Country [62] 0 0
Czechia
State/province [62] 0 0
Hradec Králové
Country [63] 0 0
Czechia
State/province [63] 0 0
Olomouc
Country [64] 0 0
Czechia
State/province [64] 0 0
Praha
Country [65] 0 0
France
State/province [65] 0 0
Chambray-lès-Tours
Country [66] 0 0
France
State/province [66] 0 0
Lille
Country [67] 0 0
France
State/province [67] 0 0
Lyon
Country [68] 0 0
France
State/province [68] 0 0
Nice
Country [69] 0 0
France
State/province [69] 0 0
Paris
Country [70] 0 0
France
State/province [70] 0 0
Pessac
Country [71] 0 0
France
State/province [71] 0 0
Poitiers Cedex
Country [72] 0 0
France
State/province [72] 0 0
Strasbourg
Country [73] 0 0
Germany
State/province [73] 0 0
Berlin
Country [74] 0 0
Germany
State/province [74] 0 0
Bochum
Country [75] 0 0
Germany
State/province [75] 0 0
Esslingen
Country [76] 0 0
Germany
State/province [76] 0 0
Frankfurt
Country [77] 0 0
Germany
State/province [77] 0 0
Halle
Country [78] 0 0
Germany
State/province [78] 0 0
Hamburg
Country [79] 0 0
Germany
State/province [79] 0 0
Hannover
Country [80] 0 0
Germany
State/province [80] 0 0
Heilbronn
Country [81] 0 0
Germany
State/province [81] 0 0
Mannheim
Country [82] 0 0
Germany
State/province [82] 0 0
Mönchengladbach
Country [83] 0 0
Germany
State/province [83] 0 0
Tuebingen
Country [84] 0 0
Germany
State/province [84] 0 0
Ulm
Country [85] 0 0
Greece
State/province [85] 0 0
Athens
Country [86] 0 0
Greece
State/province [86] 0 0
Ioánnina
Country [87] 0 0
Greece
State/province [87] 0 0
Thessaloníki
Country [88] 0 0
Hungary
State/province [88] 0 0
Budapest
Country [89] 0 0
Hungary
State/province [89] 0 0
Debrecen
Country [90] 0 0
Hungary
State/province [90] 0 0
Kaposvár
Country [91] 0 0
Hungary
State/province [91] 0 0
Szolnok
Country [92] 0 0
Israel
State/province [92] 0 0
Beer Sheva
Country [93] 0 0
Israel
State/province [93] 0 0
Haifa
Country [94] 0 0
Italy
State/province [94] 0 0
Bologna
Country [95] 0 0
Italy
State/province [95] 0 0
Meldola
Country [96] 0 0
Italy
State/province [96] 0 0
Milano
Country [97] 0 0
Italy
State/province [97] 0 0
Modena
Country [98] 0 0
Italy
State/province [98] 0 0
Piacenza
Country [99] 0 0
Italy
State/province [99] 0 0
Pisa
Country [100] 0 0
Italy
State/province [100] 0 0
Torrette
Country [101] 0 0
Italy
State/province [101] 0 0
Verona
Country [102] 0 0
Korea, Republic of
State/province [102] 0 0
Busan
Country [103] 0 0
Korea, Republic of
State/province [103] 0 0
Goyang-si
Country [104] 0 0
Korea, Republic of
State/province [104] 0 0
Gyeonggi-do
Country [105] 0 0
Korea, Republic of
State/province [105] 0 0
Seoul
Country [106] 0 0
Portugal
State/province [106] 0 0
Braga
Country [107] 0 0
Portugal
State/province [107] 0 0
Lisboa
Country [108] 0 0
Portugal
State/province [108] 0 0
Lisbon
Country [109] 0 0
Portugal
State/province [109] 0 0
Senhora da Hora
Country [110] 0 0
Portugal
State/province [110] 0 0
Vila Nova de Gaia
Country [111] 0 0
Russian Federation
State/province [111] 0 0
Chelyabinsk
Country [112] 0 0
Russian Federation
State/province [112] 0 0
Kazan
Country [113] 0 0
Russian Federation
State/province [113] 0 0
Kursk
Country [114] 0 0
Russian Federation
State/province [114] 0 0
Moscow
Country [115] 0 0
Russian Federation
State/province [115] 0 0
Novgorod
Country [116] 0 0
Russian Federation
State/province [116] 0 0
Saint-Petersburg
Country [117] 0 0
Spain
State/province [117] 0 0
Alicante
Country [118] 0 0
Spain
State/province [118] 0 0
Badajoz
Country [119] 0 0
Spain
State/province [119] 0 0
Badalona
Country [120] 0 0
Spain
State/province [120] 0 0
Barcelona
Country [121] 0 0
Spain
State/province [121] 0 0
Granada
Country [122] 0 0
Spain
State/province [122] 0 0
Madrid
Country [123] 0 0
Spain
State/province [123] 0 0
Málaga
Country [124] 0 0
Spain
State/province [124] 0 0
Pamplona
Country [125] 0 0
Spain
State/province [125] 0 0
Santander
Country [126] 0 0
Spain
State/province [126] 0 0
Zaragoza
Country [127] 0 0
United Kingdom
State/province [127] 0 0
London
Country [128] 0 0
United Kingdom
State/province [128] 0 0
Manchester
Country [129] 0 0
United Kingdom
State/province [129] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Ipsen
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/study/NCT04083235
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ipsen Medical Director
Address 0 0
Ipsen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04083235