Clinical trial NCT05383352: A Study to Compare Onivyde Manufactured at Two Different Production Sites in Adult Participants With Advanced Cancer in the Pancreas
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Pancreatic Adenocarcinoma
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2022-05-20
Enrollment: 177
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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).


Eligibility 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

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

Primary outcomes:
measure: Maximum (peak) plasma drug concentration (Cmax) of encapsulated irinotecan for Test relative to and Reference product
timeFrame: Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
measure: 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
timeFrame: Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
measure: Area under the plasma concentration-time curve from time 0 to infinity (AUC(0-∞) of encapsulated irinotecan for Test relative to Reference product
timeFrame: Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
Secondary outcomes:
measure: Maximum (peak) plasma drug concentration (Cmax) of total irinotecan for Test relative to Reference product
timeFrame: Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
measure: 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
timeFrame: Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
measure: Area under the plasma concentration-time curve from time 0 to infinity (AUC(0-∞)) of total irinotecan for Test relative to Reference product
timeFrame: Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
measure: Time to maximum plasma concentration (Tmax) of encapsulated and total irinotecan over 15-days for each Test and Reference products
timeFrame: Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
measure: Apparent clearance of drug from plasma (CL) of encapsulated and total irinotecan for Test and Reference products
timeFrame: Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
measure: Apparent volume of distribution (VZ) of encapsulated and total irinotecan for Test and Reference products
timeFrame: Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
measure: Terminal half-life (t1/2) of encapsulated and total irinotecan for Test and Reference products
timeFrame: Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
measure: Apparent terminal elimination rate constant (λZ) of encapsulated and total irinotecan for Test and Reference products
timeFrame: Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
measure: Percentage of participants with treatment-emergent adverse events (TEAEs) treatment-related leading to discontinuations, or to death
timeFrame: Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
measure: Percentage of participants with clinically significant abnormal values
timeFrame: Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
Other outcomes:
Locations:
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
city: Frankston
country: Australia
facility: Peninsula and Southeast Oncology - Frankston Private Hospital
city: Bordeaux
country: France
facility: Institut BERGONIE Centre de Lutte Contre le Cancer
city: Dijon
country: France
facility: Centre GEORGES FRANÇOIS LECLERC
city: Pierre Benite Cedex
country: France
facility: Centre Hospitalier Lyon Sud
city: Poitiers
country: France
facility: Chu La Miletrie
city: Strasbourg
country: France
facility: Centre PAUL STRAUSS
city: Dresden
country: Germany
facility: University Hospital Dresden
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona
city: Saarbrücken
country: Germany
facility: Caritasklinikum Saarbruecken St Theresia
city: Budapest
country: Hungary
facility: Mav Korhaz Es Kozponti Rendelointezet
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Gyöngyös
country: Hungary
facility: Clinexpert Kft Fázis I. Vizsgálóhely
city: Bologna
country: Italy
facility: AOU-S.Orsola-Malpighi - Universita degli Studi di Bologna
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS
city: Milano
country: Italy
facility: Instituto Europeo di Oncologia
city: Modena
country: Italy
facility: Azienda Ospedaliero Universitaria Modena
city: Torrette
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I
city: Verona
country: Italy
facility: Ospedale Borgo Roma
city: Guimarães
country: Portugal
facility: Hospital Senhora Da Oliveira - Hso-Epe
city: Lisboa
country: Portugal
facility: Centro Hospitalar Lisboa Norte - Hospital de Santa Maria
city: Lisboa
country: Portugal
facility: Fundacao Champalimaud
city: A Coruña
country: Spain
facility: Chuac Hospital Teresa Herrera
city: Badajoz
country: Spain
facility: Hospital Universitario de Badajoz
city: Barcelona
country: Spain
facility: Hospital Universitario Vall D Hebron
city: Barcelona
country: Spain
facility: Instituto Oncologico Dr Rosell Lor
city: Lleida
country: Spain
facility: Hospital Universitari de Lleida Arnaud de Villanova
city: Madrid
country: Spain
facility: Hospital Universitario Ramon Y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Quiron Salud
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Md Anserson Cancer Center
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Santiago De Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago de Compostela -Chus
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References: