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

Metastatic Pancreatic Adenocarcinoma Clinical Trial

— SIRACUSA  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05383352
• Other study ID #: D-FR-60010-015
• Secondary ID: 2021-003264-26
• Status: Recruiting
• Phase: Phase 1
• Start date: May 30, 2022
• Est. completion date: September 30, 2024

Study information

• Verified date: April 2024
• Source: Ipsen
• Contact: Ipsen Recruitment Enquiries
• Phone: See email
• Email: clinical.trials[@]ipsen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 122
• Est. completion date: September 30, 2024
• Est. primary completion date: May 27, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Metastatic Pancreatic Adenocarcinoma

Intervention

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

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Bedford Park
Australia	Peninsula and Southeast Oncology - Frankston Private Hospital	Frankston
France	Institut BERGONIE Centre de Lutte Contre le Cancer	Bordeaux
France	Centre GEORGES FRANÇOIS LECLERC	Dijon
France	Centre Hospitalier Lyon Sud	Pierre Benite Cedex
France	Chu La Miletrie	Poitiers
France	Centre PAUL STRAUSS	Strasbourg
Germany	University Hospital Dresden	Dresden
Germany	Asklepios Klinik Altona	Hamburg
Germany	Caritasklinikum Saarbruecken St Theresia	Saarbrücken
Germany	Universitätsklinikum Ulm -Zentrum Für Innere Medizin	Ulm
Hungary	Mav Korhaz Es Kozponti Rendelointezet	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Clinexpert Kft Fázis I. Vizsgálóhely	Gyöngyös
Italy	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	Milano
Italy	Azienda Ospedaliero Universitaria Modena	Modena
Italy	Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I	Torrette
Italy	Ospedale Borgo Roma	Verona
Portugal	Hospital de Braga	Braga
Portugal	Hospital Senhora Da Oliveira - Hso-Epe	Guimarães
Portugal	Centro Hospitalar Lisboa Norte - Hospital de Santa Maria	Lisboa
Portugal	Fundacao Champalimaud	Lisboa
Portugal	Instituto Portugues de Oncologia Do Porto Francisco Gentil E.P.E	Porto
Spain	Chuac Hospital Teresa Herrera	A Coruña
Spain	Hospital Universitario de Badajoz	Badajoz
Spain	Hospital Del Mar Servicio de Oncologia	Barcelona
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 General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Quiron Salud	Madrid
Spain	Hospital Universitario Ramon Y Cajal	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

Sponsors (1)

Lead Sponsor	Collaborator
Ipsen

Countries where clinical trial is conducted

Australia,  France,  Germany,  Hungary,  Italy,  Portugal,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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))
Primary	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))
Primary	Area under the plasma concentration-time curve from time 0 to infinity (AUC(0-8) 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	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))
Secondary	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))
Secondary	Area under the plasma concentration-time curve from time 0 to infinity (AUC(0-8)) 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))
Secondary	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))
Secondary	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))
Secondary	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))
Secondary	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))
Secondary	Apparent terminal elimination rate constant (?Z) 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))
Secondary	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))
Secondary	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))