Study of Nanoliposomal Irinotecan (Nal-IRI)-Containing Regimens Versus Nab-paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma
- Conditions
- Pancreatic Cancer
- Interventions
- Registration Number
- NCT02551991
- Lead Sponsor
- Ipsen
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 56
- 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)
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description nal-IRI + 5-FU/LV + oxaliplatin 5 fluorouracil - nal-IRI + 5-FU/LV + oxaliplatin Leucovorin - nal-IRI + 5-FU/LV + oxaliplatin nal-IRI - nal-IRI + 5-FU/LV + oxaliplatin Oxaliplatin -
- Primary Outcome Measures
Name Time Method Part 1A: Number of Participants With Dose-Limiting Toxicities (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 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
Name Time Method Disease Control Rate (DCR) 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.
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). 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) 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.
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). 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.
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). 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) 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.
Trial Locations
- Locations (36)
Hospital Universitario Madrid Sanchinarro Centro Integral Oncologico Clara Campal (CIOCC)
🇪🇸Madrid, Spain
Hospital General Universitario de Elche
🇪🇸Elche, Alicante, Spain
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Houston Methodist Cancer Center and Institute of Academic Medicine
🇺🇸Houston, Texas, United States
Oncology Consultants - Houston
🇺🇸Houston, Texas, United States
University of Miami
🇺🇸Miami, Florida, United States
University of South Alabama
🇺🇸Mobile, Alabama, United States
University of South Alabama - Mobile
🇺🇸Mobile, Alabama, United States
UCLA Hematology Oncology - Ventura
🇺🇸Los Angeles, California, United States
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
University of California Irvine Medical Center (UCIMC) - Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
Maryland Oncology Hematology
🇺🇸Silver Spring, Maryland, United States
Lahey Hospital & Medical Center
🇺🇸Burlington, Massachusetts, United States
Mayo Clinic Cancer Center - Rochester
🇺🇸Rochester, Minnesota, United States
Oncology Hematology West PC dba Nebraska
🇺🇸Omaha, Nebraska, United States
US Oncology - Comprehensive Cancer Centers of Nevada (CCCN)
🇺🇸Las Vegas, Nevada, United States
Holy Name Medical Center
🇺🇸Teaneck, New Jersey, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Oncology/Hematology Care Clinical Trials, LLC
🇺🇸Cincinnati, Ohio, United States
University of Oklahoma Health Sciences Center (OUHSC) Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Willamette Valley Cancer Institute & Research Center
🇺🇸Eugene, Oregon, United States
Gettysburg Cancer Center
🇺🇸Gettysburg, Pennsylvania, United States
Greenville Health System
🇺🇸Greenville, South Carolina, United States
Texas Oncology-Fort Worth 12 Ave
🇺🇸Fort Worth, Texas, United States
Medical Group of the Carolinas - Spartanburg Regional Health Services
🇺🇸Spartanburg, South Carolina, United States
Texas Oncology Methodist Dallas Cancer Center
🇺🇸Dallas, Texas, United States
Joe Arrington Cancer Research and Treatment Center - Lubbock
🇺🇸Lubbock, Texas, United States
Texas Oncology, P.A.
🇺🇸San Antonio, Texas, United States
Box Hill Hospital
🇦🇺Lilydale, Australia
Flinders Medical Centre
🇦🇺Bedford Park, Australia
St. John of God Health Care - Subiaco
🇦🇺Subiaco, Western Australia, Australia
University of Colorado (CU) Cancer Center - Anschutz Cancer Pavilion
🇺🇸Aurora, Colorado, United States
Hospital Universitario de Fuenlabrada
🇪🇸Fuenlabrada, Madrid, Spain
Mayo Clinic Cancer Center
🇺🇸Jacksonville, Florida, United States
Arizona Center for Cancer Care
🇺🇸Avondale, Arizona, United States
Eastern Maine Medical Cancer Care
🇺🇸Brewer, Maine, United States