Bioequivalence Study of Irinotecan Liposome Injection in Chinese Advanced Pancreatic Cancer.

Study Overview
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Brief Summary
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Randomized, Open-label, Single-dose, Two-sequence, Two-period, Crossover Bioequivalence Trial of Irinotecan Liposome Injection in Patients With Advanced Pancreatic Cancer.

Detailed Description
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The purpose of this study was to determine the bioequivalence of two formulations of Irinotecan Liposome Injection (70mg/m2) in Chinese patients with Advanced Pancreatic Cancer, under fasting condition. These data were to be evaluated statistically to determine if the products meet bioequivalence criteria.

Official Title
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*Official Title: Randomized, Open-label, Single-dose, Two-sequence, Two-period, Crossover Bioequivalence Trial of Irinotecan Liposome Injection in Patients With Advanced Pancreatic Cancer.

Conditions
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Advanced Pancreatic Cancer

Intervention / Treatment
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* Drug: Irinotecan Liposome Injection combined with 5-FU/LV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent for participation in the trial. Advanced pancreatic cancer diagnosed by histopathology and / or cytology. Age ≥ 18 years, men or women. BMI is above 17. ECOG score 0 to 2. Life expectancy ≥ 3 months. Adequate bone marrow function. Adequate hepatic function. Adequate renal function. Patient with reproductive potential must agree to use adequate contraception from the signing of informed consent to at least 6 months after the trial Exclusion Criteria: Patients who have a severe allergy or a significant history of hypersensitivity or an idiopathic reaction attributed to irinotecan or compounds of similar chemical composition to irinotecan ; Patients who have previously used irinotecan liposomes and experienced treatment failure or serious adverse reactions; Patients with severe cardiovascular, lung, liver, kidney, gastrointestinal, endocrine, immune system, skin, musculoskeletal, neurological or psychiatric diseases that occurred within 3 months of the first dose of the study drug, and not suitable for this study as determined by the researchers; Patients who have undergone major surgery within 4 weeks of screening or have a schedule for major surgery during the study period; Patients who have received any radiotherapy or chemotherapy and other anti-tumor treatment within 4 weeks of the first dose of the study drug, traditional Chinese medicine with anti-tumor indications within 4 weeks of the first dose of the study drug, or small molecule targeted drugs within 2 weeks (or 5 half-lives whichever is longer) of the first dose of the study drug; Patients who currently enrolled in any other clinical study, or received other investigational agents within 4 weeks of the first dose of the study drug； Blood donation or massive blood loss (>400mL) within 90 days of screening; Concomitant use of strong CYP3A4 inhibitors or inducers, or UGT1A1 inhibitors within 4 weeks of the first dose of the study drug; Patients who received certain diet (such as grapefruit) which may interfere with the evaluation of PK results; LVEF≤50%; Patients with extended QT/QTc interval (QTcF>480ms); History of alcohol or drugs abuse; Pregnant or lactating women; Patients with known Hepatitis B Virus (HBV DNA≥104), Hepatitis C Virus (anti-HCV positive, HCV RNA positive), Human immunodeficiency virus antibody (anti-HIV positive), or active Treponema Pallidum viral infection; Patients with homozygous UGT1A1*28 genotype or UGT1A1*6 genotype; Patients who are not suitable for this study as determined by the researchers.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: T-R<br>Subjects will receive Irinotecan Liposome Injection (CSPC) 70mg/m2 plus 5-FU/LV, followed by Irinotecan Liposome Injection (Ipsen) 70mg/m2 plus 5-FU/LV | Drug: Irinotecan Liposome Injection combined with 5-FU/LV<br>* Drug: Irinotecan Liposome Injection 70mg/m2 (CSPC) combined with 5-FU/LV; Drug: Irinotecan Liposome Injection 70mg/m2 (Ipsen, ONIVYDETM) combined with 5-FU/LV;<br>|
| Experimental: R-T<br>Subjects will receive Irinotecan Liposome Injection (Ipsen) 70mg/m2 plus 5-FU/LV, followed by Irinotecan Liposome Injection (CSPC) 70mg/m2 plus 5-FU/LV | Drug: Irinotecan Liposome Injection combined with 5-FU/LV<br>* Drug: Irinotecan Liposome Injection 70mg/m2 (CSPC) combined with 5-FU/LV; Drug: Irinotecan Liposome Injection 70mg/m2 (Ipsen, ONIVYDETM) combined with 5-FU/LV;<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Cmax of Total Irinotecan and Free Irinotecan will be measured for the test product (CSPC) or the reference product (Ipsen). | 0 -190 hours | 
| AUC0-t | The exposure of Total Irinotecan and Free Irinotecan from time (0) to the last quantifiable concentration (t) will be measured for the test product (CSPC) or the reference product (Ipsen). | 0 -190 hours | 
| AUC0-∞ | The exposure of Total Irinotecan and Free Irinotecan from time (0) to infinity (∞) will be calculated for the test product (CSPC) or the reference product (Ipsen). | 0 -190 hours | 
| Tmax | The time to maximum concentration will be measured for the test product (CSPC) or the reference product (Ipsen). | 0 -190 hours | 
| t1/2 | The terminal elimination half-life will be calculated for the test product (CSPC) or the reference product (Ipsen). | 0 -190 hours | 
| λz | The terminal elimination rate constant will be calculated for the test product (CSPC) or the reference product (Ipsen). | 0 -190 hours |