A Study to Evaluate the Cardiac Safety of Mitoxantrone Hydrochloride Liposome Injection in the Treatment of Advanced Malignant Tumor

Study Overview
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Brief Summary
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This is a multicenter, open-label, phase II study to evaluate the cardiac safety of Mitoxantrone Hydrochloride Liposome in patients with advanced malignant tumor who has received at least first-line treatment.

Detailed Description
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This is a multicenter, open-label, phase II study to evaluate the cardiac safety of Mitoxantrone Hydrochloride Liposome in patients with advanced malignant tumor who has received at least first-line treatment. About 120 patients will be recruited in this study. Patients with solid tumors will receive Mitoxantrone Hydrochloride Liposome 20 mg/m^2 by an intravenous infusion (IV) every 3 weeks (q3w, 1 cycle). Patients with lymphoma will receive Mitoxantrone Hydrochloride Liposome 20 mg/m^2 by an intravenous infusion (IV) every 4 weeks (q4w, 1 cycle). All the patients will receive the treatment until disease progression, intolerable toxic reaction, death, or withdrawal by investigator's or patient's decision.

Official Title
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An Open-label, Multi-center Phase II Clinical Trial to Evaluate the Cardiac Safety of Mitoxantrone Hydrochloride Liposome Injection in the Treatment of Advanced Malignant Tumor

Conditions
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Advanced Malignant Tumor

Intervention / Treatment
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* Drug: Mitoxantrone Hydrochloride Liposome


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients fully understand and voluntarily participate in this study and sign informed consent; Age ≥18 years; Histologically confirmed diagnosis of late-stage solid tumor or peripheral T cell lymphoma (PTCL); Has received standard first-line treatment; Previous treated with anthracyclines, and converted to doxorubicin at equivalent doses. The cumulative dose of doxorubicin is 160 mg/m^2 < doxorubicin ≤550 mg/m^2; Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2; Adequate organ function: Absolute neutrophil count (ANC) >1.5 10^9/L; Hemoglobin > 90 g/L; Platelet count > 75 10^9/L; Creatinine < 1.5 upper limit of normal (ULN); Total bilirubin < 1.5 ULN (< 3 ULN in patients with hepatic metastasis); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 ULN (< 5 ULN in patients with hepatic metastasis); Patients of childbearing potential must agree to use effective contraceptive measures from screening until 6 months after the end of the last dose; Female patients must have a negative pregnancy test before enrolment. Exclusion Criteria: History of allergy to mitoxantrone hydrochloride or liposomal drugs; Other malignant tumors in the past 3 years, excluding cervical carcinoma in situ, basal cell carcinoma of the skin or squamous cell carcinoma of the skin that have been radically treated; Cerebral or meningeal metastases; HBsAg or HBcAb positive with HBV DNA ≥ 2000 IU/mL, HCV antibody positive with HCV RNA above the lower limit of detection of the study center, or human immunodeficiency virus (HIV) antibody positive; Life expectancy ≤ 12 weeks; AEs from the previous treatment > Grade 1 based on CTCAE (except for the toxicity without safety risk judged by the investigator, such as alopecia, hyperpigmentation); Cardiac dysfunction, including: 1)Long QT interval syndrome; 2)High-degree atrioventricular block; 3)Malignant arrhythmia poorly controlled by medication; 4)A history of chronic heart failure with NYHA≥3; 5)Severe heart valve regurgitation or stenosis requiring treatment; 6)Acute coronary syndrome, severe pericardial disease, severe myocardial disease within 6 months prior to screening; 7)Poorly controlled hypertension (defined as systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than100 mmHg, measured ≥3 times, under control of antihypertensive drug); 8)Echocardiography showed LVEF < 50%; 8.Active bacterial or fungal infection requiring systemic intravenous therapy within 1 week before the first dose; 9.Use of other anticancer treatment within 4 weeks prior to the first dose; 10.Enrolled in any other clinical trials within 4 weeks prior to the first dose; 11.Patients underwent major surgery within 3 months prior to the first dose, or have a surgical schedule during the study period;; 12.Thrombosis or thromboembolism within 6 months prior to the first dose; 13.Lactating female; 14.Serious and/or uncontrolled systemic diseases; 15.Not suitable for this study as decided by the investigator due to other reasons.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mitoxantrone Hydrochloride Liposome Injection<br>Patients with advanced malignant tumor will receive 20 mg/m^2 Mitoxantrone Hydrochloride Liposome by an intravenous infusion (IV) on day 1 of each treatment cycle. | Drug: Mitoxantrone Hydrochloride Liposome<br>* Mitoxantrone Hydrochloride Liposome, intravenous injection (IV), 20 mg/m^2. Solid tumors: every 3 weeks (q3w, 1 cycle), Lymphoma: every 4 weeks (q4w, 1 cycle).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac adverse event |  | up to approximately 5 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) |  | up to approximately 3 years | 
| Progression-free survival (PFS) |  | up to approximately 3 years. | 
| Overall survival (OS) |  | up to approximately 5 years | 
| Incidence of treatment emergent adverse event (TEAE) |  | up to approximately 3 years. |