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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: July 23, 2022

Interventions

  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

Arms, Groups and Cohorts

  • 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).
  • 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).

Clinical Trial Outcome Measures

Primary Measures

  • 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.

Secondary Measures

  • 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.

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Ipsen
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Ipsen Medical Director, Study Director, Ipsen

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