A Study to Compare Onivyde Manufactured at Two Different Production Sites in Adult Participants With Advanced Cancer in the Pancreas

NCT ID: NCT05383352

Last Updated: 2025-04-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 177 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-30
• Study Completion Date: 2025-04-15

Brief Summary

The aim of this study is to compare Onivyde manufactured at two different production sites in adult participants with advanced cancer in the pancreas.

Adult participants with metastatic pancreatic adenocarcinoma will receive Test Product (TP) and Reference Product (RP) Onivyde in line with its approved indication. The order in which they receive them depends on the group to which they are randomly assigned, this will be referred to as the crossover phase.

The average study duration for each participant until end of crossover phase is estimated to be approximately 3 months. After completion of the crossover phase, participants who in the opinion of the investigator will benefit from the treatment will be offered to enter the extension phase where they will receive the commercial Onivyde (RP) until disease progression, withdrawal, unacceptable toxicity or death. Metastatic pancreatic adenocarcinoma is a cancer that has spread (metastasized) beyond the area of the pancreas to other organs of the body.

Onivyde is approved for the treatment of metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy, in combination with 5-fluorouracil (5-FU) and leucovorin (LV).

Conditions

Metastatic Pancreatic Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sequence RT: Reference Product followed by Test Product

Cycle 1 (Crossover Phase) Day 1: One dose Onivyde® Reference product + 5-FU/LV.

Cycle 1 (Crossover Phase) Day 15: One dose Onivyde Test product + 5-FU/LV

Cycle 2 Onwards (Extension Phase): Participants who choose to continue treatment after Cycle 1 will receive Onivyde® Reference product on Day 1 and Day 15 of every 28-day cycle in combination with 5-FU/LV

Group Type: EXPERIMENTAL

Irinotecan liposome injection

Intervention Type: DRUG

Onivyde 70 mg/m2 intravenously over 90 minutes on Cycle 1 Day 1 (Crossover Phase) and from cycle 2 onwards on Day 1 and Day 15 of every 28-day cycle (Extension Phase)

Irinotecan liposome injection

Intervention Type: DRUG

Onivyde 70 mg/m2 intravenously over 90 minutes on Cycle 1 Day 15 (Crossover Phase)

Folinic Acid

Intervention Type: DRUG

LV 400 mg/m2 intravenously over 30 minutes, on Day 1 and Day 15 of every 28-day cycle

5-Fluorouracil

Intervention Type: DRUG

5-FU 2,400 mg/m2 intravenously over 46 hours, on Day 1 and Day 15 every 28-day cycle

Sequence TR: Test Product followed by Reference Product

Cycle 1 (Crossover Phase) Day 1: One dose Onivyde Test product + 5-FU/LV.

Cycle 1 (Crossover Phase) Day 15: One dose Onivyde® Reference product + 5-FU/LV.

Cycle 2 Onwards (Extension Phase): Participants who choose to continue treatment after Cycle 1 will receive Onivyde® Reference product on Day 1 and Day 15 of every 28-day cycle in combination with 5-FU/LV.

Group Type: EXPERIMENTAL

Irinotecan liposome injection

Intervention Type: DRUG

Onivyde 70 mg/m2 intravenously over 90 minutes on Cycle 1 Day 1 (Crossover Phase)

Irinotecan liposome injection

Intervention Type: DRUG

Onivyde 70 mg/m2 intravenously over 90 minutes on Cycle 1 Day 15 (Crossover Phase) and from cycle 2 onwards on Day 1 and Day 15 of every 28-day cycle (Extension Phase)

Folinic Acid

Intervention Type: DRUG

LV 400 mg/m2 intravenously over 30 minutes, on Day 1 and Day 15 of every 28-day cycle

5-Fluorouracil

Intervention Type: DRUG

5-FU 2,400 mg/m2 intravenously over 46 hours, on Day 1 and Day 15 every 28-day cycle

Interventions

Irinotecan liposome injection

Onivyde 70 mg/m2 intravenously over 90 minutes on Cycle 1 Day 1 (Crossover Phase) and from cycle 2 onwards on Day 1 and Day 15 of every 28-day cycle (Extension Phase)

Intervention Type: DRUG

Irinotecan liposome injection

Onivyde 70 mg/m2 intravenously over 90 minutes on Cycle 1 Day 15 (Crossover Phase)

Intervention Type: DRUG

Irinotecan liposome injection

Onivyde 70 mg/m2 intravenously over 90 minutes on Cycle 1 Day 1 (Crossover Phase)

Intervention Type: DRUG

Irinotecan liposome injection

Onivyde 70 mg/m2 intravenously over 90 minutes on Cycle 1 Day 15 (Crossover Phase) and from cycle 2 onwards on Day 1 and Day 15 of every 28-day cycle (Extension Phase)

Intervention Type: DRUG

Folinic Acid

LV 400 mg/m2 intravenously over 30 minutes, on Day 1 and Day 15 of every 28-day cycle

Intervention Type: DRUG

5-Fluorouracil

5-FU 2,400 mg/m2 intravenously over 46 hours, on Day 1 and Day 15 every 28-day cycle

Intervention Type: DRUG

Other Intervention Names

Onivyde® Reference product; Onivyde Test product; Onivyde Test product; Onivyde® Reference product; Leucovorin (LV); 5-FU

Eligibility Criteria

Inclusion Criteria

• Participant must be ≥18 years of age at the time of signing the informed consent.
• Participants who have histological or cytologically confirmed adenocarcinoma of the pancreas.
• Participants with an initial diagnosis of progressive metastatic disease
• Participants with a confirmed diagnosis of metastatic adenocarcinoma of the pancreas with disease progression following gemcitabine-based therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
• Adequate haematological parameters
• Adequate hepatic function
• Adequate renal function
• Adequate coagulation
• No clinically significant abnormalities in urinalysis results
• Electrocardiogram (ECG) without any clinically significant findings
• Participants known to be infected with controlled human immunodeficiency virus (HIV)
• Male and female participants: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
• Capable of giving signed informed consent

Exclusion Criteria

• Have only localised advanced disease.
• History of any second malignancy in the last 2 years.
• Known history of central nervous system metastases
• Clinically significant gastrointestinal disorder including hepatic disorders, bleeding, inflammation, occlusion, diarrhoea >Grade 1, malabsorption syndrome, ulcerative colitis, inflammatory bowel disease or partial bowel obstruction.
• Concurrent illnesses that would be a relative contraindication to trial participation such as active cardiac or liver disease
• Active infection or an unexplained fever >38.5°C on the first scheduled day of dosing
• Neuroendocrine tumour (carcinoid, islet cell) or acinar pancreatic carcinoma
• History of interstitial lung disease, history of slowly progressive dyspnoea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.
• Exposure to a non-liposomal irinotecan or SN-38 based regimen within 4 weeks prior to randomisation, or exposure to Onivyde or other irinotecan based liposomal products within 6 weeks prior to randomisation
• Major surgery, other than diagnostic surgery, within 4 weeks prior to randomisation
• Participants who have received a live vaccine within 4 weeks prior to randomisation.
• Use of strong CYP3A inhibitors or inducers, or strong inhibitors of UGT1A1.
• Investigational therapy administered within 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior to study intervention on Cycle 1 Day 1
• Known low or absent dihydropyrimidine dehydrogenase (DPD) activity.
• Homozygous for the UGT1A1*28 allele.
• Known hypersensitivity to any of the components of Onivyde injection, other liposomal products, or any components of 5-FU, or LV
• Presence of any contraindications outlined in the Contraindications or Warnings and Precautions sections of the IB for Onivyde, or in the prescribing information for 5-FU or LV.
• Participants who, in the opinion of the investigator, have symptoms or signs suggestive of clinically unacceptable deterioration of the primary disease at the time of screening
• Any other medical or social condition deemed by the investigator to be likely to interfere with a participant's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ipsen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ipsen Medical Director

Role: STUDY_DIRECTOR

Ipsen

Locations

Flinders Medical Centre

Bedford Park, , Australia

Peninsula and Southeast Oncology - Frankston Private Hospital

Frankston, , Australia

Institut BERGONIE Centre de Lutte Contre le Cancer

Bordeaux, , France

Centre GEORGES FRANÇOIS LECLERC

Dijon, , France

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Chu La Miletrie

Poitiers, , France

Centre PAUL STRAUSS

Strasbourg, , France

University Hospital Dresden

Dresden, , Germany

Asklepios Klinik Altona

Hamburg, , Germany

Caritasklinikum Saarbruecken St Theresia

Saarbrücken, , Germany

Mav Korhaz Es Kozponti Rendelointezet

Budapest, , Hungary

Semmelweis Egyetem

Budapest, , Hungary

Clinexpert Kft Fázis I. Vizsgálóhely

Gyöngyös, , Hungary

AOU-S.Orsola-Malpighi - Universita degli Studi di Bologna

Bologna, , Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS

Meldola, , Italy

Instituto Europeo di Oncologia

Milan, , Italy

Azienda Ospedaliero Universitaria Modena

Modena, , Italy

Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I

Torrette, , Italy

Ospedale Borgo Roma

Verona, , Italy

Hospital Senhora Da Oliveira - Hso-Epe

Guimarães, , Portugal

Centro Hospitalar Lisboa Norte - Hospital de Santa Maria

Lisbon, , Portugal

Fundacao Champalimaud

Lisbon, , Portugal

Chuac Hospital Teresa Herrera

A Coruña, , Spain

Hospital Universitario de Badajoz

Badajoz, , Spain

Hospital Universitario Vall D Hebron

Barcelona, , Spain

Instituto Oncologico Dr Rosell Lor

Barcelona, , Spain

Hospital Universitari de Lleida Arnaud de Villanova

Lleida, , Spain

Hospital Universitario Ramon Y Cajal

Madrid, , Spain

Hospital Universitario Quiron Salud

Madrid, , Spain

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Md Anserson Cancer Center

Madrid, , Spain

Clinica Universidad de Navarra

Pamplona, , Spain

Hospital Universitario Marques de Valdecilla

Santander, , Spain

Complejo Hospitalario Universitario de Santiago de Compostela -Chus

Santiago de Compostela, , Spain

Countries

Australia; France; Germany; Hungary; Italy; Portugal; Spain

Other Identifiers

2021-003264-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D-FR-60010-015

Identifier Type: -

Identifier Source: org_study_id