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

NCT05383352
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Phase
Phase 1
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Recruitment status
Completed
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Participants
177
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Lead sponsor
Ipsen
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Start date
2022-05-30
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Number of sites
36
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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).
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Acronym
SIRACUSA
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Short title
A Study to Compare Onivyde Manufactured at Two Different Production Sites in Adult Participants With Advanced Cancer in the Pancreas
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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
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Completed
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Phase
Phase 1
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Study type
Interventional
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Completion date
2025-04-15
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First posted
2022-05-20
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Registry last updated
2025-04-30
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Primary completion date
2024-05-27
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Start date
2022-05-30
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Actual participants
177
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Participants
177
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Participant count basis
Actual
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Protocol amendments
4
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Number of sites
36
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
Ipsen
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05383352
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ClinicalTrials.gov ID
NCT05383352
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Registry record
Open registry record
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Allocation
Randomised
Model
Crossover
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. 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))

  2. 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))

  3. 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))

  1. 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))

  2. 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))

  3. 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))

  4. 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))

  5. 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))

  6. 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))

  7. 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))

  8. 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))

  9. 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))

    Including treatment-emergent serious adverse events

  10. 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))

    It includes clinically significant abnormal laboratory results, physical examination findings, Electrocardiogram (ECG) and vital signs

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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
Sources for eligibility
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  • Flinders Medical CentreBedford Park, Australia
  • Peninsula and Southeast Oncology - Frankston Private HospitalFrankston, Australia
  • Institut BERGONIE Centre de Lutte Contre le CancerBordeaux, France
  • Centre GEORGES FRANÇOIS LECLERCDijon, France
  • Centre Hospitalier Lyon SudPierre-Bénite, France
  • Chu La MiletriePoitiers, France
  • Centre PAUL STRAUSSStrasbourg, France
  • University Hospital DresdenDresden, Germany
  • Asklepios Klinik AltonaHamburg, Germany
  • Caritasklinikum Saarbruecken St TheresiaSaarbrücken, Germany
  • Mav Korhaz Es Kozponti RendelointezetBudapest, Hungary
  • Semmelweis EgyetemBudapest, Hungary
  • Clinexpert Kft Fázis I. VizsgálóhelyGyöngyös, Hungary
  • AOU-S.Orsola-Malpighi - Universita degli Studi di BolognaBologna, Italy
  • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCSMeldola, Italy
  • Instituto Europeo di OncologiaMilan, Italy
  • Azienda Ospedaliero Universitaria ModenaModena, Italy
  • Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto ITorrette, Italy
  • Ospedale Borgo RomaVerona, Italy
  • Hospital Senhora Da Oliveira - Hso-EpeGuimarães, Portugal
  • Centro Hospitalar Lisboa Norte - Hospital de Santa MariaLisbon, Portugal
  • Fundacao ChampalimaudLisbon, Portugal
  • Chuac Hospital Teresa HerreraA Coruña, Spain
  • Hospital Universitario de BadajozBadajoz, Spain
  • Hospital Universitario Vall D HebronBarcelona, Spain

And 11 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

Other registry identifiers

  • 2021-003264-26
Sources for references
clinicaltrials.gov

Related records

Drugs (3)

Lead sponsors (1)

Conditions (1)

Targets (2)