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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/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 - 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.
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 - Progression-free survival was defined as the time from the date of randomization to the date of disease progression, or death (any cause) on or prior to the clinical cutoff date, whichever occurred earlier. Participants who did not have disease progression or had not died were censored at the date of the last tumor assessment. Patients with two or more consecutive missing response assessments prior to a visit with documented progression (or death) were censored at the last date of tumor assessment when the patient was documented to be progression free. PFS was summarized using Kaplan-Meier methods.
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.
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 - The objective response rate was a secondary efficacy endpoint of the study and was defined by the percentage of patients in the study population with a best overall response of Complete Response (CR) or Partial Response (PR) as assessed by the investigator. Best overall response was defined per RECIST (version 1.1) recorded from randomization until progression or end of study. RECIST (v 1.1) criteria does not require confirmation of response, but an additional, more stringent analysis was also conducted, with designation of CR (or PR) requiring confirmation of response at least 4 weeks following the initial assessment of CR (or PR). Stable disease (SD) required an assessment of SD at least 6 weeks after starting treatment. Subjects with insufficient data for response classification were classified as Not Evaluable for best overall response, and as a non-responder for objective response, in the ITT population. Treatment groups are as indicated for the primary outcome of OS.
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 - Time from randomization to discontinuation of treatment for any reason, including disease progression, treatment toxicity or death.
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 - Composite measure based on patient-reported pain (per VAS), patient-reported pain medication, KPS, and weight. Clinical benefit is indicated by either:
(a) improvement in pain (less pain intensity with stable or decreased pain medication; or less pain medication with stable or decreased pain intensity) with stable or improved KPS; or (b) improvement in KPS with stable or improved pain.
With stable for KPS and pain, clinical benefit may be indicated with an observation of positive weight change.
Clinical benefit response (CBR) was classified weekly and a patient was considered a clinical benefit responder if clinical benefit was observed and maintained over a 4 week period.
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 - Tumor marker response (TMR) was evaluated by the change in CA19-9 serum levels. Response was defined as a decrease of 50% of CA19-9 in relation to the baseline level at least once during the treatment period.
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 - This patient recorded outcome consists of 15 subscales in 3 independent domains: global health-related quality of life (HRQoL), functional scales (cognitive, emotional, physical, role and social functioning), and symptom scales (appetite loss, constipation, diarrhea, dyspnea, fatigue, insomnia, nausea and vomiting, and pain). For each subscale, patients were classified as improved, worsened or stable. Improvement is indicated by achievement of subscale score at least 10% improved from baseline and maintained for at least 6 weeks. Worsened is indicated by subscale score at least 10% worse than baseline. Stable is indicated by neither improvement nor worsened. Achievement of improvement prior to worsening was classified as improvement.
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 - Plasma concentration-time data for MM-398 will be analyzed using population pharmacokinetic methods.
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
Gender
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
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United States of America
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Arizona
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United States of America
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California
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Florida
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Georgia
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Missouri
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Nevada
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New Mexico
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New York
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Ohio
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Oklahoma
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South Carolina
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Texas
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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
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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
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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
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Munich
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Germany
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Ulm
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Hungary
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Budapest
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Pecs
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Szeged
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Szolnok
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Szombathely
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Italy
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Castellana Grotte
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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
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Roma
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Korea, Republic of
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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
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Western Cape
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Spain
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Alicante
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Barcelona
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Santander
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Spain
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Valencia
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Chiayi
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Kaohsiung
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Taiching
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Tainan
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Taipei
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Taiwan
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Taoyuan
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United Kingdom
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Liverpool
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London
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Manchester
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United Kingdom
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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/show/NCT01494506
Trial related presentations / publications
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
Other publications