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

NCT05383352 | Completed Phase 1 FDA Drug

• 2 other identifiers: D-FR-60010-0152021-003264-26
• Study Type: interventional
• Target: 177
• Locations: 7 countries
• Sites: 36

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

Outcome Measures

Primary Outcomes (3)

• Maximum (peak) plasma drug concentration (Cmax) of encapsulated irinotecan for Test relative to and Reference product

  Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))

• Area under the plasma concentration-time curve from time 0 to time t (AUC(0-t) of encapsulated irinotecan for Test relative to Reference product

  Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))

• Area under the plasma concentration-time curve from time 0 to infinity (AUC(0-∞) of encapsulated irinotecan for Test relative to Reference product

  Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))

Secondary Outcomes (10)

• Maximum (peak) plasma drug concentration (Cmax) of total irinotecan for Test relative to Reference product

  Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))

• Area under the plasma concentration-time curve from time 0 to time t (AUC(0-t)) of total irinotecan for Test relative to Reference product

  Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))

• Area under the plasma concentration-time curve from time 0 to infinity (AUC(0-∞)) of total irinotecan for Test relative to Reference product

  Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))

• Time to maximum plasma concentration (Tmax) of encapsulated and total irinotecan over 15-days for each Test and Reference products

  Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))

• Apparent clearance of drug from plasma (CL) of encapsulated and total irinotecan for Test and Reference products

  Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))

Study Arms (2)

Sequence RT: Reference Product followed by Test Product

EXPERIMENTAL

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

Drug: Irinotecan liposome injection; Drug: Folinic Acid; Drug: 5-Fluorouracil

Sequence TR: Test Product followed by Reference Product

EXPERIMENTAL

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.

Drug: Irinotecan liposome injection; Drug: Folinic Acid; Drug: 5-Fluorouracil

Interventions

Irinotecan liposome injection 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)

Also known as: Onivyde® Reference product

Sequence RT: Reference Product followed by Test Product

Folinic Acid DRUG

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

Also known as: Leucovorin (LV)

Sequence RT: Reference Product followed by Test Product; Sequence TR: Test Product followed by Reference Product

5-Fluorouracil DRUG

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

Also known as: 5-FU

Sequence RT: Reference Product followed by Test Product; Sequence TR: Test Product followed by Reference Product

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ipsen: lead

Study Sites (36)

Flinders Medical Centre

Bedford Park, Australia

Location

Peninsula and Southeast Oncology - Frankston Private Hospital

Frankston, Australia

Location

Institut BERGONIE Centre de Lutte Contre le Cancer

Bordeaux, France

Location

Centre GEORGES FRANÇOIS LECLERC

Dijon, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Chu La Miletrie

Poitiers, France

Location

Centre PAUL STRAUSS

Strasbourg, France

Location

University Hospital Dresden

Dresden, Germany

Location

Asklepios Klinik Altona

Hamburg, 22763, Germany

Location

Caritasklinikum Saarbruecken St Theresia

Saarbrücken, 66113, Germany

Location

Mav Korhaz Es Kozponti Rendelointezet

Budapest, Hungary

Location

Semmelweis Egyetem

Budapest, Hungary

Location

Clinexpert Kft Fázis I. Vizsgálóhely

Gyöngyös, Hungary

Location

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

Bologna, Italy

Location

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

Meldola, Italy

Location

Instituto Europeo di Oncologia

Milan, Italy

Location

Azienda Ospedaliero Universitaria Modena

Modena, Italy

Location

Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I

Torrette, Italy

Location

Ospedale Borgo Roma

Verona, Italy

Location

Hospital Senhora Da Oliveira - Hso-Epe

Guimarães, Portugal

Location

Centro Hospitalar Lisboa Norte - Hospital de Santa Maria

Lisbon, Portugal

Location

Fundacao Champalimaud

Lisbon, Portugal

Location

Chuac Hospital Teresa Herrera

A Coruña, Spain

Location

Hospital Universitario de Badajoz

Badajoz, Spain

Location

Hospital Universitario Vall D Hebron

Barcelona, Spain

Location

Instituto Oncologico Dr Rosell Lor

Barcelona, Spain

Location

Hospital Universitari de Lleida Arnaud de Villanova

Lleida, Spain

Location

Hospital Universitario Ramon Y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Quiron Salud

Madrid, 28223, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Md Anserson Cancer Center

Madrid, Spain

Location

Clinica Universidad de Navarra

Pamplona, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, Spain

Location

Complejo Hospitalario Universitario de Santiago de Compostela -Chus

Santiago de Compostela, Spain

Location

MeSH Terms

Interventions

irinotecan sucrosofate; Leucovorin; Fluorouracil

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2022
• First Posted: May 20, 2022
• Study Start: May 30, 2022
• Primary Completion: May 27, 2024
• Study Completion: April 15, 2025
• Last Updated: April 30, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5); IT (6); PT (3); ES (14); AU (2); HU (3); DE (3)