Clinical trial NCT01494506: Study of MM-398 With or Without 5-FU/LV, Versus 5-FU/LV in Patients With Metastatic Pancreatic Cancer
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Pancreatic Cancer
Keywords: Pancreatic cancer
MM-398
PEP02
Metastatic pancreatic cancer
Gemcitabine refractory pancreatic cancer
Second line pancreatic cancer treatment
Pancreatic cancer post gemcitabine therapy
Lead sponsor: Merrimack Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2011-12-19
Enrollment: 417
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

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

Primary outcomes:
measure: Overall Survival
timeFrame: From randomization to death; until the data cut off 14 Feb 2014. The maximum time in follow up was 25 months.
Secondary outcomes:
measure: Progression Free Survival
timeFrame: 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.
measure: Objective Response Rate
timeFrame: Assessment every 6 weeks after initial response; Day 1 to data cut off of 14 Feb 2014; maximum time on study 25 months.
measure: Time to Treatment Failure
timeFrame: Randomization to treatment discontinuation (any cause). The maximum time in follow up was 25 months
measure: Percentage of Patients With Clinical Benefit Response
timeFrame: Randomization to treatment discontinuation.The maximum time in follow up was 25 months
measure: Percentage of Patients With Tumor Marker (CA 19-9) Response
timeFrame: Baseline to treatment discontinuation every 6 weeks; The maximum time in follow up was 25 months
measure: EORTC-QLQ-C30
timeFrame: Baseline to treatment discontinuation every 6 weeks; The maximum time in follow up was 25 months
measure: Pharmacokinetic Measurements of Total Irinotecan
timeFrame: 6 weeks after first study drug administration
Other outcomes:
Locations:
city: Gilbert
country: United States
state: Arizona
city: Glendale
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Burbank
country: United States
state: California
city: Duarte
country: United States
state: California
city: Fresno
country: United States
state: California
city: LaVerne
country: United States
state: California
city: San Luis Obispo
country: United States
state: California
city: Boyton Beach
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Kansas City
country: United States
state: Missouri
city: St Louis
country: United States
state: Missouri
city: Henderson
country: United States
state: Nevada
city: Albuquerque
country: United States
state: New Mexico
city: Buffalo
country: United States
state: New York
city: Columbus
country: United States
state: Ohio
city: Norman
country: United States
state: Oklahoma
city: Greenville
country: United States
state: South Carolina
city: Bedford
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Tyler
country: United States
state: Texas
city: Fairfax
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Buenos Aires
country: Argentina
city: Rosario
country: Argentina
city: Santa Fe
country: Argentina
city: Westmead
country: Australia
state: New South Wales
city: Kurralta Park
country: Australia
state: South Australia
city: Boxhill
country: Australia
state: Victoria
city: Heidelberg
country: Australia
state: Victoria
city: Melbourne
country: Australia
state: Victoria
city: Nedlands
country: Australia
state: Western Australia
city: Belo Horizonte
country: Brazil
city: Ijui
country: Brazil
city: Passo Fundo
country: Brazil
city: Porto Alegre
country: Brazil
city: Sao Paulo
country: Brazil
city: Montreal
country: Canada
state: Quebec
city: Horovice
country: Czech Republic
city: Olomouc
country: Czech Republic
city: Prague
country: Czech Republic
city: Pribram
country: Czech Republic
city: Bordeaux
country: France
city: Lille
country: France
city: Marseille
country: France
city: Berlin
country: Germany
city: Jens
country: Germany
city: Munich
country: Germany
city: Ulm
country: Germany
city: Budapest
country: Hungary
city: Pecs
country: Hungary
city: Szeged
country: Hungary
city: Szolnok
country: Hungary
city: Szombathely
country: Hungary
city: Castellana Grotte
country: Italy
city: Genova
country: Italy
city: Legnano
country: Italy
city: Naples
country: Italy
city: Roma
country: Italy
city: Hwasun-gun
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Port Elizabeth
country: South Africa
city: Pretoria
country: South Africa
city: Western Cape
country: South Africa
city: Alicante
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Santander
country: Spain
city: Valencia
country: Spain
city: Chiayi
country: Taiwan
city: Kaohsiung
country: Taiwan
city: Taiching
country: Taiwan
city: Tainan
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan
country: Taiwan
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Sutton
country: United Kingdom
Study officials:
affiliation: Merrimack Pharmaceuticals
name: Eliel Bayever, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.