Back to resultsStudy of Nanoliposomal Irinotecan (Nal-IRI)-Containing Regimens Versus Nab-paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma
Primary Purpose
Pancreatic Cancer
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
nal-IRI
5 fluorouracil
Leucovorin
Oxaliplatin
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Cancer focused on measuring Pancreatic cancer, MM-398, Metastatic pancreatic cancer, First line pancreatic cancer treatment
Eligibility Criteria
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
Sites / Locations
- University of South Alabama
- University of South Alabama - Mobile
- Arizona Center for Cancer Care
- Mayo Clinic Hospital
- UCLA Hematology Oncology - Ventura
- University of California Irvine Medical Center (UCIMC) - Chao Family Comprehensive Cancer Center
- University of Colorado (CU) Cancer Center - Anschutz Cancer Pavilion
- Mayo Clinic Cancer Center
- University of Miami
- Eastern Maine Medical Cancer Care
- Maryland Oncology Hematology
- Lahey Hospital & Medical Center
- Mayo Clinic Cancer Center - Rochester
- Oncology Hematology West PC dba Nebraska
- US Oncology - Comprehensive Cancer Centers of Nevada (CCCN)
- Holy Name Medical Center
- Roswell Park Cancer Institute
- Oncology/Hematology Care Clinical Trials, LLC
- University of Oklahoma Health Sciences Center (OUHSC) Stephenson Cancer Center
- Willamette Valley Cancer Institute & Research Center
- Gettysburg Cancer Center
- Greenville Health System
- Medical Group of the Carolinas - Spartanburg Regional Health Services
- Texas Oncology Methodist Dallas Cancer Center
- Texas Oncology-Fort Worth 12 Ave
- Houston Methodist Cancer Center and Institute of Academic Medicine
- Oncology Consultants - Houston
- Joe Arrington Cancer Research and Treatment Center - Lubbock
- Texas Oncology, P.A.
- St. John of God Health Care - Subiaco
- Flinders Medical Centre
- Box Hill Hospital
- Hospital General Universitario de Elche
- Hospital Universitario de Fuenlabrada
- Hospital Universitario Vall d'Hebron
- Hospital Universitario Madrid Sanchinarro Centro Integral Oncologico Clara Campal (CIOCC)
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
nal-IRI + 5-FU/LV + oxaliplatin
Arm Description
Outcomes
Primary Outcome Measures
Part 1A: Number of Participants With Dose-Limiting Toxicities (DLT)
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.
Secondary Outcome Measures
Median Progression Free Survival (PFS)
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.
Best Overall Response (BOR)
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.
Overall Response Rate (ORR)
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.
Disease Control Rate (DCR)
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.
Median Overall Survival (OS)
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.
Median Duration of Response (DoR)
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02551991
Brief Title
Study of Nanoliposomal Irinotecan (Nal-IRI)-Containing Regimens Versus Nab-paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
October 19, 2015 (Actual)
Primary Completion Date
February 15, 2021 (Actual)
Study Completion Date
February 15, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ipsen
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer
Keywords
Pancreatic cancer, MM-398, Metastatic pancreatic cancer, First line pancreatic cancer treatment
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
56 (Actual)
8. Arms, Groups, and Interventions
Arm Title
nal-IRI + 5-FU/LV + oxaliplatin
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
nal-IRI
Other Intervention Name(s)
MM-398
Intervention Type
Drug
Intervention Name(s)
5 fluorouracil
Other Intervention Name(s)
5-FU
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Other Intervention Name(s)
LV
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Primary Outcome Measure Information:
Title
Part 1A: Number of Participants With Dose-Limiting Toxicities (DLT)
Description
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.
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
Secondary Outcome Measure Information:
Title
Median Progression Free Survival (PFS)
Description
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.
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).
Title
Best Overall Response (BOR)
Description
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.
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).
Title
Overall Response Rate (ORR)
Description
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.
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).
Title
Disease Control Rate (DCR)
Description
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.
Time Frame
At Week 16
Title
Median Overall Survival (OS)
Description
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.
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).
Title
Median Duration of Response (DoR)
Description
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.
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).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ipsen Medical Director
Organizational Affiliation
Ipsen
Official's Role
Study Director
Facility Information:
Facility Name
University of South Alabama
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36604
Country
United States
Facility Name
University of South Alabama - Mobile
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36688
Country
United States
Facility Name
Arizona Center for Cancer Care
City
Avondale
State/Province
Arizona
ZIP/Postal Code
85392
Country
United States
Facility Name
Mayo Clinic Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
UCLA Hematology Oncology - Ventura
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of California Irvine Medical Center (UCIMC) - Chao Family Comprehensive Cancer Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
University of Colorado (CU) Cancer Center - Anschutz Cancer Pavilion
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Mayo Clinic Cancer Center
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Eastern Maine Medical Cancer Care
City
Brewer
State/Province
Maine
ZIP/Postal Code
04412
Country
United States
Facility Name
Maryland Oncology Hematology
City
Silver Spring
State/Province
Maryland
ZIP/Postal Code
20904
Country
United States
Facility Name
Lahey Hospital & Medical Center
City
Burlington
State/Province
Massachusetts
ZIP/Postal Code
01805
Country
United States
Facility Name
Mayo Clinic Cancer Center - Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Oncology Hematology West PC dba Nebraska
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68130
Country
United States
Facility Name
US Oncology - Comprehensive Cancer Centers of Nevada (CCCN)
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Facility Name
Holy Name Medical Center
City
Teaneck
State/Province
New Jersey
ZIP/Postal Code
07666
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Oncology/Hematology Care Clinical Trials, LLC
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45230
Country
United States
Facility Name
University of Oklahoma Health Sciences Center (OUHSC) Stephenson Cancer Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Willamette Valley Cancer Institute & Research Center
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97401
Country
United States
Facility Name
Gettysburg Cancer Center
City
Gettysburg
State/Province
Pennsylvania
ZIP/Postal Code
17325
Country
United States
Facility Name
Greenville Health System
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Medical Group of the Carolinas - Spartanburg Regional Health Services
City
Spartanburg
State/Province
South Carolina
ZIP/Postal Code
29303
Country
United States
Facility Name
Texas Oncology Methodist Dallas Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75203
Country
United States
Facility Name
Texas Oncology-Fort Worth 12 Ave
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Houston Methodist Cancer Center and Institute of Academic Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Oncology Consultants - Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Joe Arrington Cancer Research and Treatment Center - Lubbock
City
Lubbock
State/Province
Texas
ZIP/Postal Code
79410
Country
United States
Facility Name
Texas Oncology, P.A.
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78217
Country
United States
Facility Name
St. John of God Health Care - Subiaco
City
Subiaco
State/Province
Western Australia
ZIP/Postal Code
6008
Country
Australia
Facility Name
Flinders Medical Centre
City
Bedford Park
ZIP/Postal Code
5042
Country
Australia
Facility Name
Box Hill Hospital
City
Lilydale
ZIP/Postal Code
3140
Country
Australia
Facility Name
Hospital General Universitario de Elche
City
Elche
State/Province
Alicante
ZIP/Postal Code
03203
Country
Spain
Facility Name
Hospital Universitario de Fuenlabrada
City
Fuenlabrada
State/Province
Madrid
ZIP/Postal Code
28942
Country
Spain
Facility Name
Hospital Universitario Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario Madrid Sanchinarro Centro Integral Oncologico Clara Campal (CIOCC)
City
Madrid
ZIP/Postal Code
28050
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
34750990
Citation
Brendel K, Bekaii-Saab T, Boland PM, Dayyani F, Dean A, Macarulla T, Maxwell F, Mody K, Pedret-Dunn A, Wainberg ZA, Zhang B. Population pharmacokinetics of liposomal irinotecan in patients with cancer and exposure-safety analyses in patients with metastatic pancreatic cancer. CPT Pharmacometrics Syst Pharmacol. 2021 Dec;10(12):1550-1563. doi: 10.1002/psp4.12725. Epub 2021 Nov 20.
Results Reference
derived
PubMed Identifier
33957442
Citation
Wainberg ZA, Bekaii-Saab T, Boland PM, Dayyani F, Macarulla T, Mody K, Belanger B, Maxwell F, Moore Y, Thiagalingam A, Wang T, Zhang B, Dean A. First-line liposomal irinotecan with oxaliplatin, 5-fluorouracil and leucovorin (NALIRIFOX) in pancreatic ductal adenocarcinoma: A phase I/II study. Eur J Cancer. 2021 Jul;151:14-24. doi: 10.1016/j.ejca.2021.03.028. Epub 2021 May 4.
Results Reference
derived
PubMed Identifier
30525443
Citation
Liu X, Jiang J, Chan R, Ji Y, Lu J, Liao YP, Okene M, Lin J, Lin P, Chang CH, Wang X, Tang I, Zheng E, Qiu W, Wainberg ZA, Nel AE, Meng H. Improved Efficacy and Reduced Toxicity Using a Custom-Designed Irinotecan-Delivering Silicasome for Orthotopic Colon Cancer. ACS Nano. 2019 Jan 22;13(1):38-53. doi: 10.1021/acsnano.8b06164. Epub 2018 Dec 11.
Results Reference
derived
Learn more about this trial
Study of Nanoliposomal Irinotecan (Nal-IRI)-Containing Regimens Versus Nab-paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma
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