Comparing the Pharmacokinetic Profile of LY01612 and CAELYX® in Chinese Subjects With Advanced Breast Cancer

Study Overview
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Brief Summary
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A multicenter, randomized, open-lable, single-dose, two-cycle, double-cross bioequivalence study comparing the pharmacokinetic profile of LY01612 (Doxorubicin hydrochloride liposome injection) and CAELYX® in Chinese subjects with advanced breast cancer

Official Title
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A Multicenter, Randomized, Open-lable, Single-dose, Two-cycle, Double-cross Bioequivalence Study Comparing the Pharmacokinetic Profile of LY01612 and CAELYX® in Chinese Subjects With Advanced Breast Cancer

Conditions
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Advanced Breast Cancer

Intervention / Treatment
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* Drug: Doxorubicin hydrochloride liposome injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntary agreement to provide written informed consent; Patients aged ≥18 years and ≤75 years with locally advanced or metastatic breast cancer diagnosed by histology or cytology，and who may benefit from monotherapy of Doxorubicin liposomes; Life expectancy of at least 3 months; Eastern Cooperative Oncology Group (ECOG) performance status (PS)<2; adequate bone marrow function [leukocyte ≥3,000/mm3, absolute neutrophil count (ANC) ≥1,500/mm3, hemoglobin ≥90g/L, and platelet count ≥90,000/mm3； adequate renal function (serum creatinine ≤1.5×Institutional upper limit of normal (ULN)); adequate coagulation function [prothrombin time (PT), activated partial thromboplastin time (APTT) ≤1.5×ULN]; adequate hepatic function [aspartate aminotransferase (AST), alanine aminotransferase (ALT) level ≤ 2.5×ULN (or ≤5×ULN for subjects with liver metastases), and total bilirubin level ≤ 1.5×ULN (or ≤ 3×ULN for subjects with liver metastases). Exclusion Criteria: Patients with a diagnosis of severe cardiovascular, lung, liver, kidney, gastrointestinal, endocrine, immune system, skin, musculoskeletal, neurological or psychiatric conditions that the researchers did not consider appropriate for inclusion; With a history of myocardial infarction, unstable angina pectoris, coronary revascularization, New York Heart Association (NYHA) grade ≥Ⅱ cardiac insufficiency, severe pericardial disease, and severe unstable ventricular arrhythmia, cerebrovascular accident or transient cerebral ischemia or pulmonary embolism within 6 months before randomization; Unstable brain metastases; Electrocardiogram (ECG) QTC >480ms; left ventricular ejection fraction <50% or below the lower limit of study center value; The total cumulative dose of doxorubicin was ﹥350mg/m2 before screening； Persistent or active infection requiring systemic treatment; Pregnancy or breast feeding; Other situations that investigators consider as contra-indication for this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

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: Doxorubicin hydrochloride liposome injection(LY01612)<br>20mg/10mL, 50mg/m2, intravenously for 90min (±3min) with an infusion pump on day 1 and day 29 of the trial. | Drug: Doxorubicin hydrochloride liposome injection<br>* Doxorubicin hydrochloride liposome injection was administered intravenously for 90min (±3min) with an infusion pump on day 1 and day 29 of the trial. Doxorubicin hydrochloride liposome injection was diluted with 250mL 5% glucose injection.<br>|
| Active Comparator: Doxorubicin hydrochloride liposome injection(CAELYX®)<br>20mg/10mL, 50mg/m2, intravenously for 90min (±3min) with an infusion pump on day 1 and day 29 of the trial | Drug: Doxorubicin hydrochloride liposome injection<br>* Doxorubicin hydrochloride liposome injection was administered intravenously for 90min (±3min) with an infusion pump on day 1 and day 29 of the trial. Doxorubicin hydrochloride liposome injection was diluted with 250mL 5% glucose injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma maximum concentration (Cmax) of encapsulated doxorubicin. |  | from baseline to day 56 | 
| Area under Plasma d concentration-time curves of encapsulated doxorubicin |  | from baseline to day 56 | 
| plasma maximum concentration (Cmax) of unencapsulated doxorubicin. |  | from baseline to day 56 | 
| Area under Plasma concentration-time curves of unencapsulated doxorubicin. |  | from baseline to day 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma maximum concentration（Cmax） of total doxorubicin； |  | from baseline to day 56 | 
| Area under plasma concentration-time curves of total doxorubicin； |  | from baseline to day 56 | 
| Partial area under plasma concentration-time curves （AUC0-48h and AUC48h-t）of encapsulated doxorubicin |  | from baseline to day 56 | 
| Encapsulated doxorubicin、unencapsulated doxorubicin and total doxorubicin Tmax |  | from baseline to day 56 | 
| Encapsulated doxorubicin、unencapsulated doxorubicin and total doxorubicin t1/2z |  | from baseline to day 56 | 
| Adverse event |  | from baseline to day 56 |