Study of MM-398 With or Without 5-FU/LV, Versus 5-FU/LV in Patients With Metastatic Pancreatic Cancer

NCT ID: NCT01494506

Last Updated: 2016-06-17

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

417 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-11-30

Study Completion Date

2015-10-31

Brief Summary

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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.

Detailed Description

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Conditions

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Metastatic Pancreatic Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

MM-398

Intervention Type DRUG

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

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

5 Fluorouracil and Leucovorin IV

5 Fluorouracil and Leucovorin IV

Group Type ACTIVE_COMPARATOR

5 Fluorouracil

Intervention Type DRUG

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

Leucovorin

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

MM-398

Intervention Type DRUG

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

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

5 Fluorouracil

Intervention Type DRUG

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

Leucovorin

Intervention Type DRUG

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

Interventions

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MM-398

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

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

Intervention Type DRUG

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

Intervention Type DRUG

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 Type DRUG

Other Intervention Names

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PEP02 5-FU Folinic Acid

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merrimack Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Eliel Bayever, MD

Role: STUDY_DIRECTOR

Merrimack Pharmaceuticals

Locations

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Gilbert, Arizona, United States

Site Status

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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Ijuí, , Brazil

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Passo Fundo, , Brazil

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Porto Alegre, , Brazil

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São 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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Příbram, , 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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Pécs, , 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 City, , 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

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Countries

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United States Argentina Australia Brazil Canada Czechia France Germany Hungary Italy South Africa South Korea Spain Taiwan United Kingdom

References

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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.

Reference Type DERIVED
PMID: 33214082 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31856081 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31789476 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30842038 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30654298 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30414528 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26615328 (View on PubMed)

Other Identifiers

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MM-398-07-03-01

Identifier Type: -

Identifier Source: org_study_id

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