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

Pancreatic Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02551991
• Other study ID #: MM-398-07-02-03
• Secondary ID: 2015-003086-28
• Status: Completed
• Phase: Phase 2
• Start date: October 19, 2015
• Est. completion date: February 15, 2021

Study information

• Verified date: October 2022
• Source: Ipsen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: February 15, 2021
• Est. primary completion date: February 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• nal-IRI

• 5 fluorouracil

• Leucovorin

• Oxaliplatin

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Bedford Park
Australia	Box Hill Hospital	Lilydale
Australia	St. John of God Health Care - Subiaco	Subiaco	Western Australia
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital General Universitario de Elche	Elche	Alicante
Spain	Hospital Universitario de Fuenlabrada	Fuenlabrada	Madrid
Spain	Hospital Universitario Madrid Sanchinarro Centro Integral Oncologico Clara Campal (CIOCC)	Madrid
United States	University of Colorado (CU) Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado
United States	Arizona Center for Cancer Care	Avondale	Arizona
United States	Eastern Maine Medical Cancer Care	Brewer	Maine
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Lahey Hospital & Medical Center	Burlington	Massachusetts
United States	Oncology/Hematology Care Clinical Trials, LLC	Cincinnati	Ohio
United States	Texas Oncology Methodist Dallas Cancer Center	Dallas	Texas
United States	Willamette Valley Cancer Institute & Research Center	Eugene	Oregon
United States	Texas Oncology-Fort Worth 12 Ave	Fort Worth	Texas
United States	Gettysburg Cancer Center	Gettysburg	Pennsylvania
United States	Greenville Health System	Greenville	South Carolina
United States	Houston Methodist Cancer Center and Institute of Academic Medicine	Houston	Texas
United States	Oncology Consultants - Houston	Houston	Texas
United States	Mayo Clinic Cancer Center	Jacksonville	Florida
United States	US Oncology - Comprehensive Cancer Centers of Nevada (CCCN)	Las Vegas	Nevada
United States	UCLA Hematology Oncology - Ventura	Los Angeles	California
United States	Joe Arrington Cancer Research and Treatment Center - Lubbock	Lubbock	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	University of Oklahoma Health Sciences Center (OUHSC) Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Oncology Hematology West PC dba Nebraska	Omaha	Nebraska
United States	University of California Irvine Medical Center (UCIMC) - Chao Family Comprehensive Cancer Center	Orange	California
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	Mayo Clinic Cancer Center - Rochester	Rochester	Minnesota
United States	Texas Oncology, P.A.	San Antonio	Texas
United States	Maryland Oncology Hematology	Silver Spring	Maryland
United States	Medical Group of the Carolinas - Spartanburg Regional Health Services	Spartanburg	South Carolina
United States	Holy Name Medical Center	Teaneck	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Ipsen

Countries where clinical trial is conducted

United States,  Australia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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).
Secondary	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).
Secondary	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).
Secondary	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
Secondary	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).
Secondary	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).