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

Sponsor

Ipsen (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05383352

Collaborator

(none)

Enrollment

Locations

Arms

15.1

Anticipated Duration (Months)

3.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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-flurouracil (5-FU) and leucovorin (LV).

Condition or Disease	Intervention/Treatment	Phase
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	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

88 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official 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

Actual Study Start Date :

May 30, 2022

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Sep 1, 2023

Arms and Interventions

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 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 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) Other Names: Onivyde® Reference product Drug: Irinotecan liposome injection Onivyde 70 mg/m2 intravenously over 90 minutes on Cycle 1 Day 15 (Crossover Phase) Other Names: Onivyde Test product Drug: Folinic Acid LV 400 mg/m2 intravenously over 30 minutes, on day 1 and day 15 of every 28-day cycle Other Names: Leucovorin (LV) Drug: 5-Fluorouracil 5-FU 2,400 mg/m2 intravenously over 46 hours, on day 1 and day 15 every 28-day cycle Other Names: 5 FU
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.	Drug: Irinotecan liposome injection Onivyde 70 mg/m2 intravenously over 90 minutes on Cycle 1 Day 1 (Crossover Phase) Other Names: Onivyde Test product 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) Other Names: Onivyde® Reference product Drug: Folinic Acid LV 400 mg/m2 intravenously over 30 minutes, on day 1 and day 15 of every 28-day cycle Other Names: Leucovorin (LV) Drug: 5-Fluorouracil 5-FU 2,400 mg/m2 intravenously over 46 hours, on day 1 and day 15 every 28-day cycle Other Names: 5 FU

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 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

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)

Other Names:

Onivyde® Reference product

Drug: Irinotecan liposome injection

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

Other Names:

Onivyde Test product

Drug: Folinic Acid

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

Other Names:

Leucovorin (LV)

Drug: 5-Fluorouracil

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

Other Names:

5 FU

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.

Drug: Irinotecan liposome injection

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

Other Names:

Onivyde Test product

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)

Other Names:

Onivyde® Reference product

Drug: Folinic Acid

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

Other Names:

Leucovorin (LV)

Drug: 5-Fluorouracil

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

Other Names:

5 FU

Outcome Measures

Primary Outcome Measures

Maximum (peak) plasma drug concentration (Cmax) on encapsulated irinotecan for Test and Reference products [From Day 1 to Day 29]
Area under the plasma concentration-time curve from time 0 to time t (AUC(0-t) on encapsulated irinotecan for Test and Reference products [From Day 1 to Day 29]
Area under the plasma concentration-time curve from time 0 to infinity (AUC(0-∞) on encapsulated irinotecan for Test and Reference products [From Day 1 to Day 29]

Secondary Outcome Measures

Maximum (peak) plasma drug concentration (Cmax) on total irinotecan for Test and Reference products [From Day 1 to Day 29]
Area under the plasma concentration-time curve from time 0 to time t (AUC(0-t)) on total irinotecan for Test and Reference products. [From Day 1 to Day 29]
Area under the plasma concentration-time curve from time 0 to infinity (AUC(0-∞)) on total irinotecan for Test and Reference products [From Day 1 to Day 29]
Time to maximum plasma concentration (Tmax) of encapsulated and total irinotecan for Test and Reference products [From Day 1 to Day 29]
Apparent clearance of drug from plasma (CL) of encapsulated and total irinotecan for Test and Reference products [From Day 1 to Day 29]
Apparent volume of distribution (VZ) of encapsulated and total irinotecan for Test and Reference products [From Day 1 to Day 29]
Terminal half-life (t1/2) of encapsulated and total irinotecan for Test and Reference products [From Day 1 to Day 29]
Apparent terminal elimination rate constant (λZ) of encapsulated and total irinotecan for Test and Reference products [From Day 1 to Day 29]
Incidence of all treatment-emergent adverse events (TEAEs) treatment-related leading to discontinuations, or to death. [Baseline to 30 days after administration of last dose in Crossover Phase]
Including treatment-emergent serious adverse events
Percentage of participants with clinically significant abnormal values [Baseline to 30 days after administration of last dose in Crossover Phase]
It includes clinically significant abnormal laboratory results, physical examination findings, Electrocardiogram (ECG) and vital signs

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 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 during screening visits or 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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Institut BERGONIE Centre de Lutte Contre le Cancer	Bordeaux	France
2	CHU MORVAN -Institut de cancérologie et d'hématologie	Brest	France
3	Centre GEORGES FRANÇOIS LECLERC	Dijon	France
4	Centre Hospiltalier LYON SUD	Pierre-Bénite	France
5	Chu La Miletrie	Poitiers	France
6	Centre PAUL STRAUSS	Strasbourg	France
7	Mav Korhaz Es Kozponti Rendelointezet	Budapest	Hungary
8	Semmelweis Egyetem	Budapest	Hungary
9	Hospital de Braga	Braga	Portugal
10	Hospital Senhora Da Oliveira - Hso-Epe	Guimarães	Portugal
11	Centro Hospitalar Lisboa Norte - Hospital de Santa Maria	Lisboa	Portugal
12	Fundacao Champalimaud	Lisboa	Portugal
13	Instituto Portugues de Oncologia Do Porto Francisco Gentil E.P.E	Porto	Portugal
14	Chuac Hospital Teresa Herrera	A Coruña	Spain
15	Hospital Universitario de Badajoz	Badajoz	Spain
16	Hospital Del Mar Servicio de Oncologia	Barcelona	Spain
17	Instituto Oncologico Dr Rosell Lor	Barcelona	Spain
18	Hospital Universitari de Lleida Arnaud de Villanova	Lleida	Spain
19	Hospital Universitario Val D Hebron	Lleida	Spain
20	Hospital Universitario Ramon Y Cajal	Madrid	Spain	28034
21	Hospital General Universitario Gregorio Marañon	Madrid	Spain
22	Hospital Universitario 12 de Octobre	Madrid	Spain
23	Hospital Universitario La Paz	Madrid	Spain
24	Md Anserson Cancer Center	Madrid	Spain
25	Clinica Universidad de Navarra	Pamplona	Spain
26	Hospital Universitario Marques de Valdecilla	Santander	Spain
27	Complejo Hospitalario Universitario de Santiago de Compostela -Chus	Santiago De Compostela	Spain