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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05383352




Registration number
NCT05383352
Ethics application status
Date submitted
3/05/2022
Date registered
20/05/2022
Date last updated
1/11/2024

Titles & IDs
Public title
A Study to Compare Onivyde Manufactured at Two Different Production Sites in Adult Participants With Advanced Cancer in the Pancreas
Scientific title
A Phase I, Randomised, Open-Label, Single-Dose, Two-Treatment, Two-Way Crossover, Two-Stage Study to Evaluate the Bioequivalence of Onivyde (Irinotecan Liposome Injection) Manufactured at Two Different Sites Administered in Combination With Anti-Cancer Agents in Adult Participants With Metastatic Pancreatic Adenocarcinoma
Secondary ID [1] 0 0
2021-003264-26
Secondary ID [2] 0 0
D-FR-60010-015
Universal Trial Number (UTN)
Trial acronym
SIRACUSA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Pancreatic Adenocarcinoma 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Irinotecan liposome injection
Treatment: Drugs - Irinotecan liposome injection
Treatment: Drugs - Irinotecan liposome injection
Treatment: Drugs - Irinotecan liposome injection
Treatment: Drugs - Folinic Acid
Treatment: Drugs - 5-Fluorouracil

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 receive Onivyde® Reference product on Day 1 and Day 15 of every 28-day cycle in combination with 5-FU/LV

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 will receive Onivyde® Reference product on Day 1 and Day 15 of every 28-day cycle in combination with 5-FU/LV.


Treatment: Drugs: 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)

Treatment: Drugs: Irinotecan liposome injection
Onivyde 70 mg/m2 intravenously over 90 minutes on Cycle 1 Day 15 (Crossover Phase)

Treatment: Drugs: Irinotecan liposome injection
Onivyde 70 mg/m2 intravenously over 90 minutes on Cycle 1 Day 1 (Crossover Phase)

Treatment: Drugs: 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)

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

Treatment: Drugs: 5-Fluorouracil
5-FU 2,400 mg/m2 intravenously over 46 hours, on Day 1 and Day 15 every 28-day cycle
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum (peak) plasma drug concentration (Cmax) of encapsulated irinotecan for Test relative to and Reference product
Timepoint [1] 0 0
Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
Primary outcome [2] 0 0
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
Timepoint [2] 0 0
Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
Primary outcome [3] 0 0
Area under the plasma concentration-time curve from time 0 to infinity (AUC(0-8) of encapsulated irinotecan for Test relative to Reference product
Timepoint [3] 0 0
Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
Secondary outcome [1] 0 0
Maximum (peak) plasma drug concentration (Cmax) of total irinotecan for Test relative to Reference product
Timepoint [1] 0 0
Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
Secondary outcome [3] 0 0
Area under the plasma concentration-time curve from time 0 to infinity (AUC(0-8)) of total irinotecan for Test relative to Reference product
Timepoint [3] 0 0
Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
Secondary outcome [4] 0 0
Time to maximum plasma concentration (Tmax) of encapsulated and total irinotecan over 15-days for each Test and Reference products
Timepoint [4] 0 0
Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
Secondary outcome [5] 0 0
Apparent clearance of drug from plasma (CL) of encapsulated and total irinotecan for Test and Reference products
Timepoint [5] 0 0
Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
Secondary outcome [6] 0 0
Apparent volume of distribution (VZ) of encapsulated and total irinotecan for Test and Reference products
Timepoint [6] 0 0
Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
Secondary outcome [7] 0 0
Terminal half-life (t1/2) of encapsulated and total irinotecan for Test and Reference products
Timepoint [7] 0 0
Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
Secondary outcome [8] 0 0
Apparent terminal elimination rate constant (?Z) of encapsulated and total irinotecan for Test and Reference products
Timepoint [8] 0 0
Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
Secondary outcome [9] 0 0
Percentage of participants with treatment-emergent adverse events (TEAEs) treatment-related leading to discontinuations, or to death
Timepoint [9] 0 0
Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
Secondary outcome [10] 0 0
Percentage of participants with clinically significant abnormal values
Timepoint [10] 0 0
Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/05/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/10/2024
Actual
Sample size
Target
Accrual to date
Final
177
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [2] 0 0
Peninsula and Southeast Oncology - Frankston Private Hospital - Frankston
Recruitment postcode(s) [1] 0 0
- Bedford Park
Recruitment postcode(s) [2] 0 0
- Frankston
Recruitment outside Australia
Country [1] 0 0
France
State/province [1] 0 0
Bordeaux
Country [2] 0 0
France
State/province [2] 0 0
Dijon
Country [3] 0 0
France
State/province [3] 0 0
Pierre Benite Cedex
Country [4] 0 0
France
State/province [4] 0 0
Poitiers
Country [5] 0 0
France
State/province [5] 0 0
Strasbourg
Country [6] 0 0
Germany
State/province [6] 0 0
Dresden
Country [7] 0 0
Germany
State/province [7] 0 0
Hamburg
Country [8] 0 0
Germany
State/province [8] 0 0
Saarbrücken
Country [9] 0 0
Hungary
State/province [9] 0 0
Budapest
Country [10] 0 0
Hungary
State/province [10] 0 0
Gyöngyös
Country [11] 0 0
Italy
State/province [11] 0 0
Bologna
Country [12] 0 0
Italy
State/province [12] 0 0
Meldola
Country [13] 0 0
Italy
State/province [13] 0 0
Milano
Country [14] 0 0
Italy
State/province [14] 0 0
Modena
Country [15] 0 0
Italy
State/province [15] 0 0
Torrette
Country [16] 0 0
Italy
State/province [16] 0 0
Verona
Country [17] 0 0
Portugal
State/province [17] 0 0
Guimarães
Country [18] 0 0
Portugal
State/province [18] 0 0
Lisboa
Country [19] 0 0
Spain
State/province [19] 0 0
A Coruña
Country [20] 0 0
Spain
State/province [20] 0 0
Badajoz
Country [21] 0 0
Spain
State/province [21] 0 0
Barcelona
Country [22] 0 0
Spain
State/province [22] 0 0
Lleida
Country [23] 0 0
Spain
State/province [23] 0 0
Madrid
Country [24] 0 0
Spain
State/province [24] 0 0
Pamplona
Country [25] 0 0
Spain
State/province [25] 0 0
Santander
Country [26] 0 0
Spain
State/province [26] 0 0
Santiago De Compostela

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Ipsen
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/study/NCT05383352
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ipsen Medical Director
Address 0 0
Ipsen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Ipsen Recruitment Enquiries
Address 0 0
Country 0 0
Phone 0 0
See email
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05383352