Study of MM-398 With or Without 5-FU/LV, Versus 5-FU/LV in Patients With Metastatic Pancreatic Cancer
NAPOLI-1
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
1 other identifier
interventional
417
15 countries
79
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 Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Nov 2011
Typical duration for phase_3
79 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 2011
CompletedFirst Submitted
Initial submission to the registry
December 14, 2011
CompletedFirst Posted
Study publicly available on registry
December 19, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2015
CompletedResults Posted
Study results publicly available
February 12, 2016
CompletedJune 17, 2016
June 1, 2016
2.3 years
December 14, 2011
November 25, 2015
June 16, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Survival
Overall survival was the primary efficacy endpoint of the study and was defined as the time from the date of patient randomization to the date of death or the date the patient was last known to be alive. OS was summarized by Kaplan-Meier methodology for each treatment group. Pairwise treatment group comparisons were carried out using unstratified log rank analyses on the ITT population. Hazard ratio estimates are from Cox regression analysis. The comparison of Arm C is based only on patients who were randomized under the 3-arm version of the protocol. Consequently, the 5-FU+Leucovorin (Combo Therapy Comparison) group is a subset of all patients randomized to 5-FU+Leucovorin, which is the Mono Therapy Comparison control and contains patients randomized under both the 2-arm and 3-arm versions of the protocol.
From randomization to death; until the data cut off 14 Feb 2014. The maximum time in follow up was 25 months.
Secondary Outcomes (7)
Progression Free Survival
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.
Objective Response Rate
Assessment every 6 weeks after initial response; Day 1 to data cut off of 14 Feb 2014; maximum time on study 25 months.
Time to Treatment Failure
Randomization to treatment discontinuation (any cause). The maximum time in follow up was 25 months
Percentage of Patients With Clinical Benefit Response
Randomization to treatment discontinuation.The maximum time in follow up was 25 months
Percentage of Patients With Tumor Marker (CA 19-9) Response
Baseline to treatment discontinuation every 6 weeks; The maximum time in follow up was 25 months
- +2 more secondary outcomes
Study Arms (3)
MM-398
EXPERIMENTALMM-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.
5 Fluorouracil and Leucovorin IV
ACTIVE COMPARATOR5 Fluorouracil and Leucovorin IV
MM-398, 5-FU and Leucovorin
EXPERIMENTALMM-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.
Interventions
Arm A: MM-398 120 mg/m2 IV Q3W Arm C: MM-398 80mg/m2 IV Q2W
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
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
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- Active CNS metastasis
- Clinically significant GI disorders
- NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
- Active infection or uncontrolled fever
- Pregnant or breast feeding patients
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (79)
Unknown Facility
Gilbert, Arizona, United States
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Glendale, Arizona, United States
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Scottsdale, Arizona, United States
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Burbank, California, United States
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Duarte, California, United States
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Fresno, California, United States
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LaVerne, California, United States
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San Luis Obispo, California, United States
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Boyton Beach, Florida, United States
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Atlanta, Georgia, United States
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Kansas City, Missouri, United States
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St Louis, Missouri, United States
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Henderson, Nevada, United States
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Albuquerque, New Mexico, United States
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Buffalo, New York, United States
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Columbus, Ohio, United States
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Norman, Oklahoma, United States
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Greenville, South Carolina, United States
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Bedford, Texas, United States
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Dallas, Texas, United States
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Tyler, Texas, United States
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Fairfax, Virginia, United States
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Norfolk, Virginia, United States
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Buenos Aires, Argentina
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Rosario, Argentina
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Santa Fe, Argentina
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Westmead, New South Wales, Australia
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Kurralta Park, South Australia, Australia
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Boxhill, Victoria, Australia
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Heidelberg, Victoria, Australia
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Melbourne, Victoria, Australia
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Nedlands, Western Australia, Australia
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Belo Horizonte, Brazil
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IjuĂ, Brazil
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Passo Fundo, Brazil
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Porto Alegre, Brazil
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SĂ£o Paulo, Brazil
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Montreal, Quebec, Canada
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Hořovice, Czechia
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Olomouc, Czechia
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Prague, Czechia
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PÅ™Ăbram, Czechia
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Bordeaux, France
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Lille, France
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Marseille, France
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Berlin, Germany
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Jens, Germany
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Munich, Germany
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Ulm, Germany
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Budapest, Hungary
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PĂ©cs, Hungary
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Szeged, Hungary
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Szolnok, Hungary
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Szombathely, Hungary
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Castellana Grotte, Italy
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Genova, Italy
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Legnano, Italy
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Naples, Italy
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Roma, Italy
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Port Elizabeth, South Africa
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Pretoria, South Africa
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Western Cape, South Africa
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Hwasun-gun, South Korea
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Seoul, South Korea
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Alicante, Spain
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Barcelona, Spain
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Madrid, Spain
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Santander, Spain
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Valencia, Spain
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Chiayi City, Taiwan
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Kaohsiung City, Taiwan
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Taiching, Taiwan
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Tainan, Taiwan
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Taipei, Taiwan
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Taoyuan District, Taiwan
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Liverpool, United Kingdom
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London, United Kingdom
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Manchester, United Kingdom
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Sutton, United Kingdom
Related Publications (7)
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.
PMID: 33214082DERIVEDMacarulla 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.
PMID: 31856081DERIVEDBang 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.
PMID: 31789476DERIVEDMacarulla 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.
PMID: 30842038DERIVEDWang-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.
PMID: 30654298DERIVEDChen 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.
PMID: 30414528DERIVEDWang-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.
PMID: 26615328DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Eliel Bayever
- Organization
- Merrimack Pharmaceuticals, Inc.
Study Officials
- STUDY DIRECTOR
Eliel Bayever, MD
Merrimack Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 14, 2011
First Posted
December 19, 2011
Study Start
November 1, 2011
Primary Completion
February 1, 2014
Study Completion
October 1, 2015
Last Updated
June 17, 2016
Results First Posted
February 12, 2016
Record last verified: 2016-06