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NCT01494506 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2016-06-17

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Overall Survival

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outcome · POSTED

Progression Free Survival

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outcome · POSTED

Objective Response Rate

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outcome · POSTED

Time to Treatment Failure

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outcome · POSTED

Percentage of Patients With Clinical Benefit Response

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outcome · POSTED

Percentage of Patients With Tumor Marker (CA 19-9) Response

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outcome · POSTED

EORTC-QLQ-C30

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outcome · POSTED

Pharmacokinetic Measurements of Total Irinotecan

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
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
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    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.
    intervention Names
    1. Drug: MM-398
    label
    MM-398
    type
    EXPERIMENTAL
  2. description
    5 Fluorouracil and Leucovorin IV
    intervention Names
    1. Drug: 5 Fluorouracil
    2. Drug: Leucovorin
    label
    5 Fluorouracil and Leucovorin IV
    type
    ACTIVE_COMPARATOR
  3. description
    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.
    intervention Names
    1. Drug: MM-398
    2. Drug: 5 Fluorouracil
    3. Drug: Leucovorin
    label
    MM-398, 5-FU and Leucovorin
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. MM-398
    2. MM-398, 5-FU and Leucovorin
    description
    Arm A: MM-398 120 mg/m2 IV Q3W Arm C: MM-398 80mg/m2 IV Q2W
    name
    MM-398
    other Names
    1. PEP02
    type
    DRUG
  2. arm Group Labels
    1. 5 Fluorouracil and Leucovorin IV
    2. MM-398, 5-FU and Leucovorin
    description
    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
    name
    5 Fluorouracil
    other Names
    1. 5-FU
    type
    DRUG
  3. arm Group Labels
    1. 5 Fluorouracil and Leucovorin IV
    2. MM-398, 5-FU and Leucovorin
    description
    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
    name
    Leucovorin
    other Names
    1. Folinic Acid
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
417
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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.
    measure
    Overall Survival
    time Frame
    From randomization to death; until the data cut off 14 Feb 2014. The maximum time in follow up was 25 months.
secondary Outcomes
  1. description
    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.
    measure
    Progression Free Survival
    time Frame
    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.
  2. description
    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.
    measure
    Objective Response Rate
    time Frame
    Assessment every 6 weeks after initial response; Day 1 to data cut off of 14 Feb 2014; maximum time on study 25 months.
  3. description
    Time from randomization to discontinuation of treatment for any reason, including disease progression, treatment toxicity or death.
    measure
    Time to Treatment Failure
    time Frame
    Randomization to treatment discontinuation (any cause). The maximum time in follow up was 25 months
  4. description
    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.
    measure
    Percentage of Patients With Clinical Benefit Response
    time Frame
    Randomization to treatment discontinuation.The maximum time in follow up was 25 months
  5. description
    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.
    measure
    Percentage of Patients With Tumor Marker (CA 19-9) Response
    time Frame
    Baseline to treatment discontinuation every 6 weeks; The maximum time in follow up was 25 months
  6. description
    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.
    measure
    EORTC-QLQ-C30
    time Frame
    Baseline to treatment discontinuation every 6 weeks; The maximum time in follow up was 25 months
  7. description
    Plasma concentration-time data for MM-398 will be analyzed using population pharmacokinetic methods.
    measure
    Pharmacokinetic Measurements of Total Irinotecan
    time Frame
    6 weeks after first study drug administration
Full study description
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.
Source references
references
  1. 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.
    pmid
    33214082
    type
    DERIVED
  2. 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.
    pmid
    31856081
    type
    DERIVED
  3. 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.
    pmid
    31789476
    type
    DERIVED
  4. 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.
    pmid
    30842038
    type
    DERIVED
  5. 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.
    pmid
    30654298
    type
    DERIVED
  6. 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.
    pmid
    30414528
    type
    DERIVED
  7. 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.
    pmid
    26615328
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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      1. context
        Updated: February 12, 2025
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        February 12, 2025

    Preserved source evidence · Not medical advice