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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

Registration Number
NCT04083235
Lead Sponsor
Ipsen
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 available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
770
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Irinotecan liposome injection + Oxaliplatin + 5-FU/LVIrinotecan Liposomal InjectionIrinotecan liposome injection, oxaliplatin, 5 FU/LV, will be administered on Days 1 and 15 of each 28-day cycle (until progression or unacceptable toxicity).
Irinotecan liposome injection + Oxaliplatin + 5-FU/LV5FluorouracilIrinotecan liposome injection, oxaliplatin, 5 FU/LV, will be administered on Days 1 and 15 of each 28-day cycle (until progression or unacceptable toxicity).
Irinotecan liposome injection + Oxaliplatin + 5-FU/LVLeucovorinIrinotecan liposome injection, oxaliplatin, 5 FU/LV, will be administered on Days 1 and 15 of each 28-day cycle (until progression or unacceptable toxicity).
Nab-paclitaxel + GemcitabineNab-paclitaxelNab-paclitaxel and gemcitabine will be administered on Days 1, 8 and 15 of each 28-day cycle (until progression or unacceptable toxicity).
Irinotecan liposome injection + Oxaliplatin + 5-FU/LVOxaliplatinIrinotecan liposome injection, oxaliplatin, 5 FU/LV, will be administered on Days 1 and 15 of each 28-day cycle (until progression or unacceptable toxicity).
Nab-paclitaxel + GemcitabineGemcitabineNab-paclitaxel and gemcitabine will be administered on Days 1, 8 and 15 of each 28-day cycle (until progression or unacceptable toxicity).
Primary Outcome Measures
NameTimeMethod
Overall Survival (OS)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 Outcome Measures
NameTimeMethod
Progression Free Survival (PFS)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)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.

Trial Locations

Locations (199)

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

Banner Health- MD Anderson Cancer Center

🇺🇸

Gilbert, Arizona, United States

Mayo Clinic - Scottsdale

🇺🇸

Phoenix, Arizona, United States

Comprehensive Blood And Cancer Center

🇺🇸

Bakersfield, California, United States

University of California- Irvine Health Cancer Cente

🇺🇸

Costa Mesa, California, United States

City of Hope National Medical Center

🇺🇸

Duarte, California, United States

University of California, Los Angeles (UCLA)

🇺🇸

Los Angeles, California, United States

St. Jude Hospital Yorba Linda dba St. Joseph Heritage Healthcare

🇺🇸

Orange, California, United States

University of California - Irvine Medical Center

🇺🇸

Orange, California, United States

Torrance Memorial Physician Network Cancer Care

🇺🇸

Redondo Beach, California, United States

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University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States

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