Clinical trial NCT02551991: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: Pancreatic cancer
MM-398
Metastatic pancreatic cancer
First line pancreatic cancer treatment
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2015-09-16
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Part 1A: Number of Participants With Dose-Limiting Toxicities (DLT)
timeFrame: 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:
measure: Median Progression Free Survival (PFS)
timeFrame: 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).
measure: Best Overall Response (BOR)
timeFrame: 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).
measure: Overall Response Rate (ORR)
timeFrame: 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).
measure: Disease Control Rate (DCR)
timeFrame: At Week 16
measure: Median Overall Survival (OS)
timeFrame: 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).
measure: Median Duration of Response (DoR)
timeFrame: 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).
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama
state: Alabama
city: Mobile
country: United States
facility: University of South Alabama - Mobile
state: Alabama
city: Avondale
country: United States
facility: Arizona Center for Cancer Care
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Los Angeles
country: United States
facility: UCLA Hematology Oncology - Ventura
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center (UCIMC) - Chao Family Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado (CU) Cancer Center - Anschutz Cancer Pavilion
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic Cancer Center
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Brewer
country: United States
facility: Eastern Maine Medical Cancer Care
state: Maine
city: Silver Spring
country: United States
facility: Maryland Oncology Hematology
state: Maryland
city: Burlington
country: United States
facility: Lahey Hospital & Medical Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center - Rochester
state: Minnesota
city: Omaha
country: United States
facility: Oncology Hematology West PC dba Nebraska
state: Nebraska
city: Las Vegas
country: United States
facility: US Oncology - Comprehensive Cancer Centers of Nevada (CCCN)
state: Nevada
city: Teaneck
country: United States
facility: Holy Name Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Cincinnati
country: United States
facility: Oncology/Hematology Care Clinical Trials, LLC
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center (OUHSC) Stephenson Cancer Center
state: Oklahoma
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute & Research Center
state: Oregon
city: Gettysburg
country: United States
facility: Gettysburg Cancer Center
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville Health System
state: South Carolina
city: Spartanburg
country: United States
facility: Medical Group of the Carolinas - Spartanburg Regional Health Services
state: South Carolina
city: Dallas
country: United States
facility: Texas Oncology Methodist Dallas Cancer Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology-Fort Worth 12 Ave
state: Texas
city: Houston
country: United States
facility: Houston Methodist Cancer Center and Institute of Academic Medicine
state: Texas
city: Houston
country: United States
facility: Oncology Consultants - Houston
state: Texas
city: Lubbock
country: United States
facility: Joe Arrington Cancer Research and Treatment Center - Lubbock
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Subiaco
country: Australia
facility: St. John of God Health Care - Subiaco
state: Western Australia
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
city: Lilydale
country: Australia
facility: Box Hill Hospital
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Alicante
city: Fuenlabrada
country: Spain
facility: Hospital Universitario de Fuenlabrada
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Madrid Sanchinarro Centro Integral Oncologico Clara Campal (CIOCC)
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References:
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.
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.
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.