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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01494506




Registration number
NCT01494506
Ethics application status
Date submitted
14/12/2011
Date registered
19/12/2011
Date last updated
17/06/2016

Titles & IDs
Public title
Study of MM-398 With or Without 5-FU/LV, Versus 5-FU/LV in Patients With Metastatic Pancreatic Cancer
Scientific title
A Randomized, Open Label Phase 3 Study of MM-398, With or Without 5-Fluorouracil and Leucovorin, Versus 5 Fluorouracil and Leucovorin in Patients With Metastatic Pancreatic Cancer Who Have Failed Prior Gemcitabine-based Therapy
Secondary ID [1] 0 0
MM-398-07-03-01
Universal Trial Number (UTN)
Trial acronym
NAPOLI-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Pancreatic Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MM-398
Treatment: Drugs - 5 Fluorouracil
Treatment: Drugs - Leucovorin

Experimental: MM-398 - MM-398 120 mg/m2 Q3W IV. Note: The published dose of ONIVYDE was expressed as the irinotecan hydrochloride trihydrate until October 2015. It is now expressed as the irinotecan free base. Converting a dose based on irinotecan hydrochloride trihydrate to a dose based on irinotecan free base is accomplished by substituting the Molecular Weight of irinotecan hydrochloride trihydrate (677.19 g/mole) with the Molecular Weight of irinotecan free base (586.68 g/mole), which results in a conversion factor of 0.866. 120 mg/m2 dose of irinotecan hydrochloride trihydrate is equivalent to 100 mg/ m2 of irinotecan free base.

Active comparator: 5 Fluorouracil and Leucovorin IV - 5 Fluorouracil and Leucovorin IV

Experimental: MM-398, 5-FU and Leucovorin - MM-398 80 mg/m2, 5-FU and Leucovorin Q2W IV. Note: The published dose of ONIVYDE was expressed as the irinotecan hydrochloride trihydrate until October 2015. It is now expressed as the irinotecan free base. Converting a dose based on irinotecan hydrochloride trihydrate to a dose based on irinotecan free base is accomplished by substituting the Molecular Weight of irinotecan hydrochloride trihydrate (677.19 g/mole) with the Molecular Weight of irinotecan free base (586.68 g/mole), which results in a conversion factor of 0.866. 80 mg/m2 dose of irinotecan hydrochloride trihydrate is equivalent to 70 mg/ m2 of irinotecan free base.


Treatment: Drugs: MM-398
Arm A: MM-398 120 mg/m2 IV Q3W

Arm C: MM-398 80mg/m2 IV Q2W

Treatment: Drugs: 5 Fluorouracil
Arm B: 5 Fluorouracil 2000 mg/m2 IV for 4 weeks followed by 2 weeks of rest every 6 weeks

Arm C: 5 Fluorouracil 2400 mg/m2 IV every 2 weeks

Treatment: Drugs: Leucovorin
Arm B: Leucovorin 200 mg/m2 IV for 4 weeks followed by 2 weeks of rest every 6 weeks

Arm C: Leucovorin 400 mg/m2 IV every 2 weeks
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
From randomization to death; until the data cut off 14 Feb 2014. The maximum time in follow up was 25 months.
Secondary outcome [1] 0 0
Progression Free Survival
Timepoint [1] 0 0
Randomization until disease progression or death from any cause; Until the data cut off of 14 Feb 2014. The maximum time in follow up was 25 months.
Secondary outcome [2] 0 0
Objective Response Rate
Timepoint [2] 0 0
Assessment every 6 weeks after initial response; Day 1 to data cut off of 14 Feb 2014; maximum time on study 25 months.
Secondary outcome [3] 0 0
Time to Treatment Failure
Timepoint [3] 0 0
Randomization to treatment discontinuation (any cause). The maximum time in follow up was 25 months
Secondary outcome [4] 0 0
Percentage of Patients With Clinical Benefit Response
Timepoint [4] 0 0
Randomization to treatment discontinuation.The maximum time in follow up was 25 months
Secondary outcome [5] 0 0
Percentage of Patients With Tumor Marker (CA 19-9) Response
Timepoint [5] 0 0
Baseline to treatment discontinuation every 6 weeks; The maximum time in follow up was 25 months
Secondary outcome [6] 0 0
EORTC-QLQ-C30
Timepoint [6] 0 0
Baseline to treatment discontinuation every 6 weeks; The maximum time in follow up was 25 months
Secondary outcome [7] 0 0
Pharmacokinetic Measurements of Total Irinotecan
Timepoint [7] 0 0
6 weeks after first study drug administration

Eligibility
Key inclusion criteria
* Histologically or cytologically confirmed adenocarcinoma of the exocrine pancreas
* Metastatic disease
* Documented disease progression after prior gemcitabine based therapy
* KPS >/= 70
* Adequate bone marrow function
* Adequate hepatic function
* Adequate renal function
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Active CNS metastasis
* Clinically significant GI disorders
* Severe arterial thromboembolic events less than 6 months before inclusion
* NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
* Active infection or uncontrolled fever
* Pregnant or breast feeding patients

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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/10/2015
Sample size
Target
Accrual to date
Final
417
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
- Westmead
Recruitment hospital [2] 0 0
- Kurralta Park
Recruitment hospital [3] 0 0
- Boxhill
Recruitment hospital [4] 0 0
- Heidelberg
Recruitment hospital [5] 0 0
- Melbourne
Recruitment hospital [6] 0 0
- Nedlands
Recruitment postcode(s) [1] 0 0
- Westmead
Recruitment postcode(s) [2] 0 0
- Kurralta Park
Recruitment postcode(s) [3] 0 0
- Boxhill
Recruitment postcode(s) [4] 0 0
- Heidelberg
Recruitment postcode(s) [5] 0 0
- Melbourne
Recruitment postcode(s) [6] 0 0
- Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
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California
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United States of America
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Florida
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United States of America
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Georgia
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United States of America
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Missouri
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United States of America
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Nevada
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United States of America
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New Mexico
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United States of America
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New York
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United States of America
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Ohio
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United States of America
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Oklahoma
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United States of America
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South Carolina
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United States of America
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Texas
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United States of America
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Virginia
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Argentina
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Buenos Aires
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Argentina
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Rosario
Country [16] 0 0
Argentina
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Santa Fe
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Brazil
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Belo Horizonte
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Brazil
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Ijui
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Brazil
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Passo Fundo
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Brazil
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Porto Alegre
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Brazil
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Sao Paulo
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Canada
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Quebec
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Czech Republic
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Horovice
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Czech Republic
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Olomouc
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Czech Republic
State/province [25] 0 0
Prague
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Czech Republic
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Pribram
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France
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Bordeaux
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France
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Lille
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France
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Marseille
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Germany
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Berlin
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Germany
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Jens
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Germany
State/province [32] 0 0
Munich
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Germany
State/province [33] 0 0
Ulm
Country [34] 0 0
Hungary
State/province [34] 0 0
Budapest
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Hungary
State/province [35] 0 0
Pecs
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Hungary
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Szeged
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Hungary
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Szolnok
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Hungary
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Szombathely
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Italy
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Castellana Grotte
Country [40] 0 0
Italy
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Genova
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Italy
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Legnano
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Italy
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Naples
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Italy
State/province [43] 0 0
Roma
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Korea, Republic of
State/province [44] 0 0
Hwasun-gun
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Korea, Republic of
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Seoul
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South Africa
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Port Elizabeth
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South Africa
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Pretoria
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South Africa
State/province [48] 0 0
Western Cape
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Spain
State/province [49] 0 0
Alicante
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Santander
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Spain
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Valencia
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Taiwan
State/province [54] 0 0
Chiayi
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Taiwan
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Kaohsiung
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Taiwan
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Taiching
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Taiwan
State/province [57] 0 0
Tainan
Country [58] 0 0
Taiwan
State/province [58] 0 0
Taipei
Country [59] 0 0
Taiwan
State/province [59] 0 0
Taoyuan
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Liverpool
Country [61] 0 0
United Kingdom
State/province [61] 0 0
London
Country [62] 0 0
United Kingdom
State/province [62] 0 0
Manchester
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Sutton

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

Ethics approval
Ethics application status

Summary
Brief summary
The study is an open label, randomized phase 3 study of MM-398 with or without 5-Fluorouracil (5-FU) and Leucovorin (also known as folinic acid), versus 5-FU and leucovorin in metastatic pancreatic cancer patients who have progressed on prior gemcitabine based therapy.
Trial website
https://clinicaltrials.gov/study/NCT01494506
Trial related presentations / publications
Chen LT, Macarulla T, Blanc JF, Mirakhur B, de Jong FA, Belanger B, Bekaii-Saab T, Siveke JT. Early dose reduction/delay and the efficacy of liposomal irinotecan with fluorouracil and leucovorin in metastatic pancreatic ductal adenocarcinoma (mPDAC): A post hoc analysis of NAPOLI-1. Pancreatology. 2021 Jan;21(1):192-199. doi: 10.1016/j.pan.2020.10.029. Epub 2020 Oct 10.
Macarulla Mercade T, Chen LT, Li CP, Siveke JT, Cunningham D, Bodoky G, Blanc JF, Lee KH, Dean A, Belanger B, Wang-Gillam A. Liposomal Irinotecan + 5-FU/LV in Metastatic Pancreatic Cancer: Subgroup Analyses of Patient, Tumor, and Previous Treatment Characteristics in the Pivotal NAPOLI-1 Trial. Pancreas. 2020 Jan;49(1):62-75. doi: 10.1097/MPA.0000000000001455. Erratum In: Pancreas. 2020 Mar;49(3):e27. doi: 10.1097/MPA.0000000000001517.
Bang YJ, Li CP, Lee KH, Chiu CF, Park JO, Shan YS, Kim JS, Chen JS, Shim HJ, Rau KM, Choi HJ, Oh DY, Belanger B, Chen LT. Liposomal irinotecan in metastatic pancreatic adenocarcinoma in Asian patients: Subgroup analysis of the NAPOLI-1 study. Cancer Sci. 2020 Feb;111(2):513-527. doi: 10.1111/cas.14264. Epub 2019 Dec 20.
Macarulla T, Blanc JF, Wang-Gillam A, Chen LT, Siveke JT, Mirakhur B, Chen J, de Jong FA. Liposomal irinotecan and 5-fluorouracil/leucovorin in older patients with metastatic pancreatic cancer - A subgroup analysis of the pivotal NAPOLI-1 trial. J Geriatr Oncol. 2019 May;10(3):427-435. doi: 10.1016/j.jgo.2019.02.011. Epub 2019 Mar 4.
Wang-Gillam A, Hubner RA, Siveke JT, Von Hoff DD, Belanger B, de Jong FA, Mirakhur B, Chen LT. NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: Final overall survival analysis and characteristics of long-term survivors. Eur J Cancer. 2019 Feb;108:78-87. doi: 10.1016/j.ejca.2018.12.007. Epub 2019 Jan 14.
Chen LT, Siveke JT, Wang-Gillam A, Li CP, Bodoky G, Dean AP, Shan YS, Jameson GS, Macarulla T, Lee KH, Cunningham D, Blanc JF, Chiu CF, Schwartsmann G, Braiteh FS, Mamlouk K, Belanger B, de Jong FA, Hubner RA. Survival with nal-IRI (liposomal irinotecan) plus 5-fluorouracil and leucovorin versus 5-fluorouracil and leucovorin in per-protocol and non-per-protocol populations of NAPOLI-1: Expanded analysis of a global phase 3 trial. Eur J Cancer. 2018 Dec;105:71-78. doi: 10.1016/j.ejca.2018.09.010. Epub 2018 Nov 8.
Wang-Gillam A, Li CP, Bodoky G, Dean A, Shan YS, Jameson G, Macarulla T, Lee KH, Cunningham D, Blanc JF, Hubner RA, Chiu CF, Schwartsmann G, Siveke JT, Braiteh F, Moyo V, Belanger B, Dhindsa N, Bayever E, Von Hoff DD, Chen LT; NAPOLI-1 Study Group. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet. 2016 Feb 6;387(10018):545-557. doi: 10.1016/S0140-6736(15)00986-1. Epub 2015 Nov 29. Erratum In: Lancet. 2016 Feb 6;387(10018):536. doi: 10.1016/S0140-6736(15)01306-9.
Public notes

Contacts
Principal investigator
Name 0 0
Eliel Bayever, MD
Address 0 0
Merrimack Pharmaceuticals
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/NCT01494506