A Study To Compare Onivyde Manufactured At Two Different Production Sites In Adult Participants With Advanced Cancer In The Pancreas

Study Overview

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

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).

N/A

Metastatic Pancreatic Adenocarcinoma

DRUG: Irinotecan liposome injection
DRUG: Irinotecan liposome injection
DRUG: Irinotecan liposome injection
DRUG: Irinotecan liposome injection
DRUG: Folinic Acid
DRUG: 5-Fluorouracil

D-FR-60010-015
2021-003264-26 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2022-05-03	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-04-29
First Submitted that Met QC Criteria 2022-05-16	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-04-30
First Posted (ACTUAL) 2022-05-20	Results First Posted N/A	Last Verified 2025-04

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Crossover

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: 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	DRUG: 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) DRUG: Irinotecan liposome injection Onivyde 70 mg/m2 intravenously over 90 minutes on Cycle 1 Day 15 (Crossover Phase) DRUG: Folinic Acid LV 400 mg/m2 intravenously over 30 minutes, on Day 1 and Day 15 of every 28-day cycle DRUG: 5-Fluorouracil 5-FU 2,400 mg/m2 intravenously over 46 hours, on Day 1 and Day 15 every 28-day cycle
EXPERIMENTAL: 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 wil	DRUG: Irinotecan liposome injection Onivyde 70 mg/m2 intravenously over 90 minutes on Cycle 1 Day 1 (Crossover Phase) 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) DRUG: Folinic Acid LV 400 mg/m2 intravenously over 30 minutes, on Day 1 and Day 15 of every 28-day cycle DRUG: 5-Fluorouracil 5-FU 2,400 mg/m2 intravenously over 46 hours, on Day 1 and Day 15 every 28-day cycle

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: 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

DRUG: 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)

DRUG: Irinotecan liposome injection

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

DRUG: Folinic Acid

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

DRUG: 5-Fluorouracil

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

EXPERIMENTAL: 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 wil

DRUG: Irinotecan liposome injection

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

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)

DRUG: Folinic Acid

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

DRUG: 5-Fluorouracil

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

Primary Outcome Measures	Measure Description	Time Frame
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 Outcome Measures	Measure Description	Time Frame
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))
Apparent volume of distribution (VZ) 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))
Terminal half-life (t1/2) 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))
Apparent terminal elimination rate constant (λZ) 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))
Percentage of participants with treatment-emergent adverse events (TEAEs) treatment-related leading to discontinuations, or to death	Including treatment-emergent serious adverse events	Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
Percentage of participants with clinically significant abnormal values	It includes clinically significant abnormal laboratory results, physical examination findings, Electrocardiogram (ECG) and vital signs	Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Ipsen Medical Director, Ipsen

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Clinical Trial Record