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Trial record 1 of 1 for:    D-FR-60010-015_SIRACUSA
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A Study to Compare Onivyde Manufactured at Two Different Production Sites in Adult Participants With Advanced Cancer in the Pancreas (SIRACUSA)

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ClinicalTrials.gov Identifier: NCT05383352
Recruitment Status : Recruiting
First Posted : May 20, 2022
Last Update Posted : January 26, 2023
Sponsor:
Information provided by (Responsible Party):
Ipsen

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: Folinic Acid Drug: 5-Fluorouracil Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : September 2023

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 Name: Onivyde® Reference product

Drug: Irinotecan liposome injection
Onivyde 70 mg/m2 intravenously over 90 minutes on Cycle 1 Day 15 (Crossover Phase)
Other Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 5 FU




Primary Outcome Measures :
  1. Maximum (peak) plasma drug concentration (Cmax) on encapsulated irinotecan for Test and Reference products [ Time Frame: From Day 1 to Day 29 ]
  2. Area under the plasma concentration-time curve from time 0 to time t (AUC(0-t) on encapsulated irinotecan for Test and Reference products [ Time Frame: From Day 1 to Day 29 ]
  3. Area under the plasma concentration-time curve from time 0 to infinity (AUC(0-∞) on encapsulated irinotecan for Test and Reference products [ Time Frame: From Day 1 to Day 29 ]

Secondary Outcome Measures :
  1. Maximum (peak) plasma drug concentration (Cmax) on total irinotecan for Test and Reference products [ Time Frame: From Day 1 to Day 29 ]
  2. Area under the plasma concentration-time curve from time 0 to time t (AUC(0-t)) on total irinotecan for Test and Reference products. [ Time Frame: From Day 1 to Day 29 ]
  3. Area under the plasma concentration-time curve from time 0 to infinity (AUC(0-∞)) on total irinotecan for Test and Reference products [ Time Frame: From Day 1 to Day 29 ]
  4. Time to maximum plasma concentration (Tmax) of encapsulated and total irinotecan for Test and Reference products [ Time Frame: From Day 1 to Day 29 ]
  5. Apparent clearance of drug from plasma (CL) of encapsulated and total irinotecan for Test and Reference products [ Time Frame: From Day 1 to Day 29 ]
  6. Apparent volume of distribution (VZ) of encapsulated and total irinotecan for Test and Reference products [ Time Frame: From Day 1 to Day 29 ]
  7. Terminal half-life (t1/2) of encapsulated and total irinotecan for Test and Reference products [ Time Frame: From Day 1 to Day 29 ]
  8. Apparent terminal elimination rate constant (λZ) of encapsulated and total irinotecan for Test and Reference products [ Time Frame: From Day 1 to Day 29 ]
  9. Incidence of all treatment-emergent adverse events (TEAEs) treatment-related leading to discontinuations, or to death. [ Time Frame: Baseline to 30 days after administration of last dose in Crossover Phase ]
    Including treatment-emergent serious adverse events

  10. Percentage of participants with clinically significant abnormal values [ Time Frame: 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05383352


Contacts
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Contact: Ipsen Recruitment Enquiries See email clinical.trials@ipsen.com

Locations
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Sponsors and Collaborators
Ipsen
Investigators
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Study Director: Ipsen Medical Director Ipsen
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Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT05383352    
Other Study ID Numbers: D-FR-60010-015
2021-003264-26 ( EudraCT Number )
First Posted: May 20, 2022    Key Record Dates
Last Update Posted: January 26, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Leucovorin
Folic Acid
Fluorouracil
Irinotecan
Camptothecin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antidotes
Protective Agents
Vitamin B Complex
Vitamins
Micronutrients
Hematinics
Antineoplastic Agents, Phytogenic