A Study to Evaluate the Safety and Efficacy of PLM60 in Advanced HCC

Study Overview
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Brief Summary
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This is a dose escalation study based on 3+3 design with the aim to establish MTD and provide RP2D. PLM60 is to administered by multi-cycle intravenous infusion.

Official Title
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A Single-arm, Open-label, Single-center Phase Ib Study to Evaluate the Safety and Efficacy of Liposome-entrapped Mitoxantrone Hydrochloride Injection (PLM60) in Advanced Hepatocellular Carcinoma (HCC)

Conditions
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Advanced Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Liposome-entrapped Mitoxantrone Hydrochloride Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent from the patient； ECOG performance status of 0 or 1; Histologically/cytologically confirmed diagnosis of advanced HCC; Adequate washout period for previous anti-tumor therapy; Measurable disease according to RECIST v1.1; Life expectancy ≥ 12 weeks; Adequate organ function; Child-Pugh grade A or partial grade B; BCLC stage B or C;V Exclusion Criteria: Prior treatment with Mitoxantrone or Liposome-entrapped Mitoxantrone, or other anthracyclines, with the total cumulative dose of > 360 mg/m2 ; Any drug-related adverse event derived from any previous anti-tumor treatment, excluding alopecia, Pigmentation, or other toxicity with little safety risk for subjects, that has not recovered to grade1 or less; Active central nervous system (CNS) metastases (brain or leptomeningeal metastases, etc.); Any history of other malignancy within 5 years; Untreated hepatitis infection; HIV positive; History of liver transplantation, severe cirrhosis, hepatic encephalopathy; Inadequate cardiac function; Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: PLM60<br>Three dose levels will be tested according to the 3 + 3 dose-escalation design.The dose-limiting toxicity (DLT) will be assessed from the first administration of PLM60 to the end of the first cycle (28 days). | Drug: Liposome-entrapped Mitoxantrone Hydrochloride Injection<br>* Intravenous infusion<br>* Other names: PLM60;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limited toxicity (DLT) | To identify the dose-limited toxicity (DLT). | 1year | 
| Maximum tolerated dose (MTD) | To identify the maximum tolerated dose (MTD). | 1 year | 
| Recommended Phase II Dose (RP2D) | To identify the Recommended Phase II Dose (RP2D) | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) | To preliminarily evaluate the AUC in patients with advanced HCC. | 2 years | 
| Peak Plasma Concentration (Cmax) | To preliminarily evaluate Cmax in patients with advanced HCC. | 2 years | 
| Time of peak plasma concentration (Tmax) | To preliminarily evaluate Tmax in patients with advanced HCC. | 2 years | 
| Median overall survival (OS) | To preliminarily evaluate ORR in patients with advanced HCC. | 2 years | 
| Median progression free survival (PFS) | To preliminarily evaluate PFS in patients with advanced HCC. | 2 years | 
| Overall response rate (ORR) | To preliminarily evaluate ORR in patients with advanced HCC. | 2 years | 
| Duration of Response (DoR) | To preliminarily evaluate DoR in patients with advanced HCC. | 2 years |