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: Recruiting
• First Posted: September 10, 2019
• Last Update Posted: March 30, 2021
• Sponsor: Ipsen
• Information provided by (Responsible Party): Ipsen

Tracking Information

• First Submitted Date: September 6, 2019
• First Posted Date: September 10, 2019
• Last Update Posted Date: March 30, 2021
• Actual Study Start Date: February 19, 2020
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 24, 2020): Overall survival (OS) [ Time Frame: From study start until 565 OS events have occurred (approximately 15 months after last patient enrollment) ]
• 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: July 24, 2020)

• Progression free survival (PFS) [ Time Frame: From study start until 565 OS events have occurred (approximately 15 months after last patient enrollment) ]
• Overall Response Rate (ORR) [ Time Frame: From study start until 565 OS events have occurred (approximately 15 months after last patient enrollment) ]

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: Recruiting
• Estimated Enrollment (submitted: September 6, 2019): 750
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2023
• Estimated Primary Completion Date: December 31, 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 tumours 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: Ipsen Recruitment Enquiries; see email; clinical.trials@ipsen.com

Contact: MassiveBio US Recruitment Enquiries; 1-855-NAPOLI3 (855-627-6543); napoli3@massivebio.com

• Listed Location Countries: Australia, Austria, Belgium, Brazil, Canada, Czechia, France, Germany, Greece, Hungary, Israel, Italy, Korea, Republic of, Portugal, Russian Federation, Spain, Sweden, United Kingdom, United States

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: Where patient data can be anonymised, Ipsen will share all individual participant data that underlie the results reported in the published journal article with qualified researchers who provide a valid research question. Study documents, such as the study protocol and clinical study report, are not always available.
• Time Frame: Data are available beginning 6 months and ending 5 years after the publication of the findings in a journal; after this time, only raw data may be available.
• Access Criteria: Proposals should be submitted to DataSharing@ipsen.com and will be assessed by a scientific review board.

• Responsible Party: Ipsen
• Study Sponsor: Ipsen
• Collaborators: Not Provided

Investigators

• Study Director: Ipsen Medical Director; Ipsen

• PRS Account: Ipsen
• Verification Date: March 2021