A Study to Assess the Effectiveness and Safety of Irinotecan Liposome Injection, 5-fluorouracil/Leucovorin Plus Oxaliplatin in Patients Not Previously Treated for Metastatic Pancreatic Cancer, Compared to Nab-paclitaxel+Gemcitabine Treatment (NAPOLI 3)

• ClinicalTrials.gov Identifier: NCT04083235
• Recruitment Status: Active, not recruiting
• First Posted: September 10, 2019
• Results First Posted: March 13, 2024
• Last Update Posted: April 30, 2024
• Sponsor: Ipsen
• Information provided by (Responsible Party): Ipsen

Tracking Information

• First Submitted Date: September 6, 2019
• First Posted Date: September 10, 2019
• Results First Submitted Date: February 15, 2024
• Results First Posted Date: March 13, 2024
• Last Update Posted Date: April 30, 2024
• Actual Study Start Date: February 11, 2020
• Actual Primary Completion Date: July 23, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 15, 2024)

Overall Survival (OS) [ Time Frame: 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 up to DCO date of 23 July 2022 (maximum of 893 days) ]

The OS was defined as time from the date of randomization to the date of death due to any cause. Participants who did not have a date of death recorded at the time of the final analysis were censored at the last known time that the participant was alive. The median OS was measured using Kaplan-Meier technique.

• Original Primary Outcome Measures (submitted: September 6, 2019): Overall survival (OS) [ Time Frame: From study start until 564 OS events have occurred (approximately 15 months after last patient enrollment) ]

Current Secondary Outcome Measures (submitted: February 15, 2024)

• Progression Free Survival (PFS) [ Time Frame: Assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose until EoT visit (maximum of 893 days) ]
  PFS was defined as the time from the date of randomization to the first documented disease progression using response evaluation criteria in solid tumors (RECIST) Version 1.1 as per Investigator assessment or death due to any cause. The median PFS was measured using Kaplan-Meier technique.
• Overall Response Rate (ORR) [ Time Frame: Assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose until EoT visit, (maximum of 893 days) ]
  The ORR was defined as the percentage of participants with a best overall response (BOR) characterized as either a complete response (CR) or partial response (PR) per RECIST Version 1.1. BOR was defined as the best response as recorded from randomization until documented objective disease progression using RECIST Version 1.1. As per RECIST version 1.1, CR is disappearance of all target lesions; PR is >=30% decrease in the sum of the longest diameter of target lesions; and overall response = CR + PR. The ORR was calculated using Clopper-Pearson method.

Original Secondary Outcome Measures (submitted: September 6, 2019)

• Progression free survival (PFS) [ Time Frame: From study start until 564 OS events have occurred (approximately 15 months after last patient enrollment) ]
• Overall Response Rate (ORR) [ Time Frame: From study start until 564 OS events have occurred (approximately 15 months after last patient enrollment) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Assess the Effectiveness and Safety of Irinotecan Liposome Injection, 5-fluorouracil/Leucovorin Plus Oxaliplatin in Patients Not Previously Treated for Metastatic Pancreatic Cancer, Compared to Nab-paclitaxel+Gemcitabine Treatment
• Official Title: An Open-label, Randomised, Multicentre, Phase III Study of Irinotecan Liposome Injection, Oxaliplatin, 5-fluorouracil/Leucovorin Versus Nab-paclitaxel Plus Gemcitabine in Subjects Who Have Not Previously Received Chemotherapy for Metastatic Adenocarcinoma of the Pancreas
• Brief Summary: The purpose of this study is to look at the efficacy and safety of Irinotecan liposome injection in combination with other approved drugs used for cancer therapy, namely 5 fluorouracil/leucovorin (5FU/LV) plus oxaliplatin compared to nab-paclitaxel + gemcitabine treatment in improving the overall survival of patients not previously treated for metastatic pancreatic cancer.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Adenocarcinoma of the Pancreas

Intervention

• Drug: Irinotecan Liposomal Injection
  Irinotecan liposome injection is irinotecan in the form of the sucrosofate salt, encapsulated in liposomes for i.v. infusion. It is supplied in sterile, single-use vials containing 10 mL of irinotecan liposome injection at a concentration of 4.3 mg/mL free base equivalent (FBE).
  Other Names:

  • Onivyde®
  • Nal-IRI
• Drug: Oxaliplatin
  Oxaliplatin injection, USP is supplied in single-dose vials containing 50 mg, 100 mg or 200 mg of oxaliplatin as a sterile, preservative-free, aqueous solution at a concentration of 5 mg/mL.
  Other Name: Eloxatin®
• Drug: 5Fluorouracil
  Fluorouracil injection, USP is a colorless to faint yellow, aqueous, sterile, nonpyrogenic injectable solution available in 50 mL and 100 mL pharmacy bulk package. Each mL contains 50 mg fluorouracil in water for injection, USP.
  Other Names:

  • Adrucil®
  • flurouracil
  • 5-FU
• Drug: Leucovorin
  Leucovorin Calcium for Injection is supplied in vials ranging from 50-500 mg and available as an injectable solution or lyophilized powder for reconstitution.
  Other Name: Folinic Acid
• Drug: Nab-paclitaxel
  Nab-paclitaxel is a lyophilised powder containing 100 or 250 mg of paclitaxel formulated as albumin-bound particles in single-use vials for re-constitution. Each mL of the reconstituted formulation will contain 5 mg/mL paclitaxel.
  Other Name: Abraxane®
• Drug: Gemcitabine
  Gemcitabine for injection is a lyophilised powder for solution for infusion, with each single use vial containing 200 mg, 1 g or 2 g of gemcitabine.
  Other Name: Gemzar®

Study Arms

• Experimental: Irinotecan liposome injection + Oxaliplatin + 5-FU/LV
  Irinotecan liposome injection, oxaliplatin, 5 FU/LV, will be administered on Days 1 and 15 of each 28-day cycle (until progression or unacceptable toxicity).
  Interventions:

  • Drug: Irinotecan Liposomal Injection
  • Drug: Oxaliplatin
  • Drug: 5Fluorouracil
  • Drug: Leucovorin
• Active Comparator: Nab-paclitaxel + Gemcitabine
  Nab-paclitaxel and gemcitabine will be administered on Days 1, 8 and 15 of each 28-day cycle (until progression or unacceptable toxicity).
  Interventions:

  • Drug: Nab-paclitaxel
  • Drug: Gemcitabine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: August 11, 2022): 770
• Original Estimated Enrollment (submitted: September 6, 2019): 750
• Estimated Study Completion Date: December 31, 2024
• Actual Primary Completion Date: July 23, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histological or cytologically confirmed adenocarcinoma of the pancreas that has not been previously treated in the metastatic setting.
• Initial diagnosis of metastatic disease must have occurred ≤6 weeks prior to screening.
• Subject has one or more metastatic lesions measurable by computed tomography (CT) scan (or magnetic resonance imaging (MRI), if the subject is allergic to CT contrast media) according to RECIST Version 1.1 criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Subject has adequate biological parameters as demonstrated by the following blood counts:(a) Absolute neutrophil count (ANC) ≥2000/mm3 without the use of hemopoietic growth factors within the last 7 days prior to randomisation (b) Platelet count ≥100,000/mm3 (c) Haemoglobin (Hgb) ≥9 g/dL obtained ≤14 days prior to randomisation.
• Adequate hepatic function as evidenced by: (a) Serum total bilirubin ≤1.5x ULN (biliary drainage is allowed for biliary obstruction), and (b) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5x upper limit of normal (ULN) (≤5x ULN is acceptable if liver metastases are present).
• Adequate renal function as evidenced by creatinine clearance ≥30 mL/min.
• Adequate coagulation studies (obtained ≤14 days prior to randomisation) as demonstrated by prothrombin time and partial thromboplastin time within normal limits (≤1.5xULN ).

Exclusion Criteria:

• Prior treatment of pancreatic cancer in the metastatic setting with surgery, radiotherapy, chemotherapy or investigational therapy
• Prior treatment of pancreatic adenocarcinoma with chemotherapy in the adjuvant setting, except those where at least 12 months have elapsed since completion of the last dose and no persistent treatment-related toxicities are present.
• Subject has only localised advanced disease.
• Documented serum albumin <3 g/dL
• Known history of central nervous system (CNS) metastases.
• Clinically significant gastrointestinal disorder
• History of any second malignancy in the last 2 years
• Concurrent illnesses that would be a relative contraindication to trial participation
• Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1
• Neuroendocrine (carcinoid, islet cell) or acinar pancreatic carcinoma
• Known low or absent dihydropyrimidine dehydrogenase (DPD) activity

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Brazil, Canada, Czechia, France, Germany, Greece, Hungary, Israel, Italy, Korea, Republic of, Portugal, Russian Federation, Spain, United Kingdom, United States
• Removed Location Countries: Sweden

Administrative Information

• NCT Number: NCT04083235
• Other Study ID Numbers: D-US-60010-001; 2018-003585-14 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants.
• Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
• Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).
• URL: https://vivli.org/members/ourmembers/

• Current Responsible Party: Ipsen
• Original Responsible Party: Same as current
• Current Study Sponsor: Ipsen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Ipsen Medical Director; Ipsen

• PRS Account: Ipsen
• Verification Date: April 2024