Study of Nanoliposomal Irinotecan (Nal-IRI)-Containing Regimens Versus Nab-paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma
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
2 other identifiers
interventional
56
3 countries
36
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2 pancreatic-cancer
Started Oct 2015
Typical duration for phase_2 pancreatic-cancer
36 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 10, 2015
CompletedFirst Posted
Study publicly available on registry
September 16, 2015
CompletedStudy Start
First participant enrolled
October 19, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 15, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
February 15, 2021
CompletedResults Posted
Study results publicly available
October 10, 2022
CompletedOctober 10, 2022
October 1, 2022
5.3 years
September 10, 2015
May 20, 2022
October 7, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
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 Outcomes (6)
Median Progression Free Survival (PFS)
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)
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)
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)
At Week 16
Median Overall Survival (OS)
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).
- +1 more secondary outcomes
Study Arms (1)
nal-IRI + 5-FU/LV + oxaliplatin
EXPERIMENTALInterventions
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Ipsenlead
Study Sites (36)
University of South Alabama
Mobile, Alabama, 36604, United States
University of South Alabama - Mobile
Mobile, Alabama, 36688, United States
Arizona Center for Cancer Care
Avondale, Arizona, 85392, United States
Mayo Clinic Hospital
Phoenix, Arizona, 85054, United States
UCLA Hematology Oncology - Ventura
Los Angeles, California, 90095, United States
University of California Irvine Medical Center (UCIMC) - Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
University of Colorado (CU) Cancer Center - Anschutz Cancer Pavilion
Aurora, Colorado, 80045, United States
Mayo Clinic Cancer Center
Jacksonville, Florida, 32224, United States
University of Miami
Miami, Florida, 33136, United States
Eastern Maine Medical Cancer Care
Brewer, Maine, 04412, United States
Maryland Oncology Hematology
Silver Spring, Maryland, 20904, United States
Lahey Hospital & Medical Center
Burlington, Massachusetts, 01805, United States
Mayo Clinic Cancer Center - Rochester
Rochester, Minnesota, 55905, United States
Oncology Hematology West PC dba Nebraska
Omaha, Nebraska, 68130, United States
US Oncology - Comprehensive Cancer Centers of Nevada (CCCN)
Las Vegas, Nevada, 89169, United States
Holy Name Medical Center
Teaneck, New Jersey, 07666, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Oncology/Hematology Care Clinical Trials, LLC
Cincinnati, Ohio, 45230, United States
University of Oklahoma Health Sciences Center (OUHSC) Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104, United States
Willamette Valley Cancer Institute & Research Center
Eugene, Oregon, 97401, United States
Gettysburg Cancer Center
Gettysburg, Pennsylvania, 17325, United States
Greenville Health System
Greenville, South Carolina, 29605, United States
Medical Group of the Carolinas - Spartanburg Regional Health Services
Spartanburg, South Carolina, 29303, United States
Texas Oncology Methodist Dallas Cancer Center
Dallas, Texas, 75203, United States
Texas Oncology-Fort Worth 12 Ave
Fort Worth, Texas, 76104, United States
Houston Methodist Cancer Center and Institute of Academic Medicine
Houston, Texas, 77030, United States
Oncology Consultants - Houston
Houston, Texas, 77030, United States
Joe Arrington Cancer Research and Treatment Center - Lubbock
Lubbock, Texas, 79410, United States
Texas Oncology, P.A.
San Antonio, Texas, 78217, United States
St. John of God Health Care - Subiaco
Subiaco, Western Australia, 6008, Australia
Flinders Medical Centre
Bedford Park, 5042, Australia
Box Hill Hospital
Lilydale, 3140, Australia
Hospital General Universitario de Elche
Elche, Alicante, 03203, Spain
Hospital Universitario de Fuenlabrada
Fuenlabrada, Madrid, 28942, Spain
Hospital Universitario Vall d'Hebron
Barcelona, 08035, Spain
Hospital Universitario Madrid Sanchinarro Centro Integral Oncologico Clara Campal (CIOCC)
Madrid, 28050, Spain
Related Publications (3)
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.
PMID: 34750990DERIVEDWainberg 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.
PMID: 33957442DERIVEDLiu 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.
PMID: 30525443DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The comparative Part 2 was removed in a protocol amendment, dated 11 April 2018, before it was initiated, as this comparative part of the study is being undertaken as a stand-alone Phase 3 study D-US-60010-001.
Results Point of Contact
- Title
- Medical Director
- Organization
- Ipsen Bioscience, Inc.
Study Officials
- STUDY DIRECTOR
Ipsen Medical Director
Ipsen
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 10, 2015
First Posted
September 16, 2015
Study Start
October 19, 2015
Primary Completion
February 15, 2021
Study Completion
February 15, 2021
Last Updated
October 10, 2022
Results First Posted
October 10, 2022
Record last verified: 2022-10