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

Study Overview

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.

N/A

Pancreatic Cancer

DRUG: nal-IRI
DRUG: 5 fluorouracil
DRUG: Leucovorin
DRUG: Oxaliplatin

MM-398-07-02-03
2015-003086-28 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )

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 Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2015-09-10	Results First Submitted 2022-05-20	Last Update Submitted that met QC Criteria 2022-10-07
First Submitted that Met QC Criteria 2015-09-15	Results First Submitted that Met QC Criteria 2022-10-07	Last Update Posted (ACTUAL) 2022-10-10
First Posted (ACTUAL) 2015-09-16	Results First Posted 2022-10-10	Last Verified 2022-10

Study Plan

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

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: nal-IRI + 5-FU/LV + oxaliplatin	DRUG: nal-IRI DRUG: 5 fluorouracil DRUG: Leucovorin DRUG: Oxaliplatin

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: nal-IRI + 5-FU/LV + oxaliplatin

DRUG: nal-IRI

DRUG: 5 fluorouracil

DRUG: Leucovorin

DRUG: Oxaliplatin

Primary Outcome Measures	Measure Description	Time Frame
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 Outcome Measures	Measure Description	Time Frame
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.	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)	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)	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)	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)	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)	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).

Contacts and Locations

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

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

Collaborators and Investigators

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

Investigators

STUDY_DIRECTOR: Ipsen Medical Director, Ipsen

Publications

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

General Publications

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.
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.
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.

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