Study of Nanoliposomal Irinotecan (Nal-IRI)-Containing Regimens Versus Nab-paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma

October 7, 2022 updated by: Ipsen

A Randomized, Open-label Phase 2 Study of Nanoliposomal Irinotecan (Nal-IRI)-Containing Regimens Versus Nab-Paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma

This is an open-label, phase 2 non-comparative study to assess the safety, tolerability, and preliminary efficacy of nal-IRI in combination with other anticancer therapies in patients not previously treated for metastatic pancreatic adenocarcinoma. This study will assess the following regimen:

• nal-IRI + 5-fluorouracil (5-FU)/leucovorin (LV) + oxaliplatin

The study will be conducted in two parts:

Part 1, consisting of an initial dose exploration (Part 1A) followed by dose expansion (Part 1B) of the irinotecan liposome injection +5-FU/LV + oxaliplatin regimen and Part 2, consisting of a comparison of irinotecan liposome injection-containing regimen versus nab-paclitaxel plus gemcitabine. The comparative Part 2 was removed in a protocol amendment, dated 11 April 2018 (Version 6.0), before it was initiated, as this comparative part of the study is being undertaken as a stand-alone phase III study D-US-60010-001. This CSR only pertains to the single-arm dose exploration and dose expansion Part 1 results and no further reference is made to the comparative Part 2.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

56

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Bedford Park, Australia, 5042
        • Flinders Medical Centre
      • Lilydale, Australia, 3140
        • Box Hill Hospital
    • Western Australia
      • Subiaco, Western Australia, Australia, 6008
        • St. John of God Health Care - Subiaco
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitario Vall d'Hebron
      • Madrid, Spain, 28050
        • Hospital Universitario Madrid Sanchinarro Centro integral Oncologico Clara Campal (CIOCC)
    • Alicante
      • Elche, Alicante, Spain, 03203
        • Hospital General Universitario de Elche
    • Madrid
      • Fuenlabrada, Madrid, Spain, 28942
        • Hospital Universitario de Fuenlabrada
  • United States
    • Alabama
      • Mobile, Alabama, United States, 36604
        • University of South Alabama
      • Mobile, Alabama, United States, 36688
        • University of South Alabama - Mobile
    • Arizona
      • Avondale, Arizona, United States, 85392
        • Arizona Center for Cancer Care
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic Hospital
    • California
      • Los Angeles, California, United States, 90095
        • UCLA Hematology Oncology - Ventura
      • Orange, California, United States, 92868
        • University of California Irvine Medical Center (UCIMC) - Chao Family Comprehensive Cancer Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado (CU) Cancer Center - Anschutz Cancer Pavilion
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic Cancer Center
      • Miami, Florida, United States, 33136
        • University of Miami
    • Maine
      • Brewer, Maine, United States, 04412
        • Eastern Maine Medical Cancer Care
    • Maryland
      • Silver Spring, Maryland, United States, 20904
        • Maryland Oncology Hematology
    • Massachusetts
      • Burlington, Massachusetts, United States, 01805
        • Lahey Hospital & Medical Center
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Cancer Center - Rochester
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Oncology Hematology West PC dba Nebraska
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • US Oncology - Comprehensive Cancer Centers of Nevada (CCCN)
    • New Jersey
      • Teaneck, New Jersey, United States, 07666
        • Holy Name Medical Center
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
    • Ohio
      • Cincinnati, Ohio, United States, 45230
        • Oncology/Hematology Care Clinical Trials, LLC
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center (OUHSC) Stephenson Cancer Center
    • Oregon
      • Eugene, Oregon, United States, 97401
        • Willamette Valley Cancer Institute & Research Center
    • Pennsylvania
      • Gettysburg, Pennsylvania, United States, 17325
        • Gettysburg Cancer Center
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • Greenville Health System
      • Spartanburg, South Carolina, United States, 29303
        • Medical Group of the Carolinas - Spartanburg Regional Health Services
    • Texas
      • Dallas, Texas, United States, 75203
        • Texas Oncology Methodist Dallas Cancer Center
      • Fort Worth, Texas, United States, 76104
        • Texas Oncology-Fort Worth 12 Ave
      • Houston, Texas, United States, 77030
        • Houston Methodist Cancer Center and Institute of Academic Medicine
      • Houston, Texas, United States, 77030
        • Oncology Consultants - Houston
      • Lubbock, Texas, United States, 79410
        • Joe Arrington Cancer Research and Treatment Center - Lubbock
      • San Antonio, Texas, United States, 78217
        • Texas Oncology, P.A.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed adenocarcinoma of the pancreas that has not been previously treated in the metastatic setting
  • Unresectable, locally advanced or metastatic disease; diagnosed within 6 weeks prior to screening
  • At least one tumor lesion measurable by CT or MRI scan (according to RECIST v1.1)
  • ECOG performance status of 0 or 1 at screening and within 72 hours prior to first dose if first dose occurs more than 72 hours post-screening
  • Adequate hematological, hepatic, renal and cardiac function
  • Recovered from the effects of any prior surgery or radiotherapy
  • Patient has a Karnofsky performance status (KPS) ≥ 70 at Screening, and within 72 hours prior to date of first dose if first dose occurs more than 72 hours after screening (Part 1B only)

Exclusion Criteria:

  • Prior treatment of pancreatic cancer in the metastatic setting (or locally advanced setting) with surgery (placement of stent is allowed), radiotherapy, chemotherapy or investigational therapy
  • Prior treatment of pancreatic cancer with chemotherapy in adjuvant setting, except those where at least 12 months have elapsed since completion of the last dose and no persistent treatment-related toxicities present
  • Uncontrolled Central Nervous System (CNS) metastases
  • Clinically significant gastrointestinal disorder
  • History of any second malignancy in the last 3 years. Patients with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible
  • Presence of any contraindications for nal-IRI, irinotecan, 5-FU, leucovorin, oxaliplatin
  • Use of strong CYP3A4 or inducers or presence of any other contra indications for irinotecan
  • Pregnant or breast feeding
  • Neuroendocrine or acinar pancreatic carcinoma
  • Serum albumin < 3 g/dL at screening visit and within 72 hours prior to first dose if first dose occurs more than 72 hours post screening
  • Patients with symptoms and signs of clinically unacceptable deterioration of primary disease at time of screening
  • Previous treatment with irinotecan-based, nab-paclitaxel-based or gemcitabine-based resulting in disease progression

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: nal-IRI + 5-FU/LV + oxaliplatin
Drug: Oxaliplatin
Drug: Leucovorin
Other Names:
  • LV
Drug: nal-IRI
Other Names:
  • MM-398
Drug: 5 fluorouracil
Other Names:
  • 5-FU

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1A: Number of Participants With Dose-Limiting Toxicities (DLT)
Time Frame: From the start of the first study treatment (Cycle 1 Day 1) up to 14 days after the second dose of study treatment, maximum of 42 days
Adverse events (AEs) were considered to be DLTs if they occurred during the safety evaluation period (i.e, 28 days of Cycle 1; or 14 days after the second dose of study treatment if there was a treatment delay) and were deemed related to the study treatment regimen. Any AE that was related to disease progression was not considered a DLT.
From the start of the first study treatment (Cycle 1 Day 1) up to 14 days after the second dose of study treatment, maximum of 42 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Progression Free Survival (PFS)
Time Frame: RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, end of treatment (EoT) visit, then every 2 months thereafter (maximum of 278 weeks).
The PFS was defined as the time from date of first study treatment to the first documented radiographical progression of disease (PD), per investigator using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, or death from any cause, whichever comes first. The PFS was calculated using Kaplan-Meier technique.
RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, end of treatment (EoT) visit, then every 2 months thereafter (maximum of 278 weeks).
Best Overall Response (BOR)
Time Frame: RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).
The BOR was defined as the best response (complete response [CR] + partial response [PR] + stable disease [SD]) recorded from the start of study treatment until disease progression or start of new anticancer therapy using RECIST Version 1.1.
RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).
Overall Response Rate (ORR)
Time Frame: RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).
The ORR was defined as the percentage of participants with a BOR characterized as either a CR or PR relative to the total number of evaluable participants using RECIST Version 1.1. Evaluable participants were defined as treated participants with measurable disease at baseline.
RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).
Disease Control Rate (DCR)
Time Frame: At Week 16
The DCR was defined as percentage of participants with CR or PR or SD or Non-PD/Non-CR, per RECIST Version 1.1 relative to total number of treated participants with measurable disease at baseline.
At Week 16
Median Overall Survival (OS)
Time Frame: RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).
The OS was the time from date of first study treatment to the date of death from any cause. Participant survival data were collected from all available sources. The OS was calculated using Kaplan-Meier technique.
RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).
Median Duration of Response (DoR)
Time Frame: RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).
The DoR was defined as the time from the first date of response (CR or PR) to first date of documented radiographical PD, per investigator using RECIST Version 1.1. This only applied to participants with CR or PR. If a participant was given a new anticancer therapy prior to first response, DoR was not calculated. The DoR was calculated using Kaplan-Meier technique.
RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ipsen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 19, 2015

Primary Completion (Actual)

February 15, 2021

Study Completion (Actual)

February 15, 2021

Study Registration Dates

First Submitted

September 10, 2015

First Submitted That Met QC Criteria

September 15, 2015

First Posted (Estimate)

September 16, 2015

Study Record Updates

Last Update Posted (Actual)

October 10, 2022

Last Update Submitted That Met QC Criteria

October 7, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MM-398-07-02-03
  • 2015-003086-28 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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