A Study of Docetaxel Polymeric Micelles for Injection in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This study is an open, multi-cohort phase II clinical trial, the overall design is divided into two parts: dose confirmation stage and expansion stage. Dose confirmation stage is to evaluate the safety and tolerability of three dosing regimenes of docetaxel polymer micelle for injection in patients with advanced esophageal cancer, and to determine the best dosing regimenes for entering the expansion stage. The expansion stage iwas used to evaluate the efficacy and further safety of the best dosing regimen identified in the dose confirmation stage in patients with advanced solid tumors. All subjects in the dose confirmation stage and expansion stage will continue treatment according to the injection docetaxel micelle regimen they received at enrollment until the disease progresses or the investigator determines that continuing treatment with the study drug will not benefit, or any intolerable toxicity occurs, or they voluntarily withdraw, or for other reasons, whichever occurs first.

Official Title
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An Open, Multi-cohort, Phase II Clinical Study Evaluating the Efficacy and Safety of Docetaxel Polymer Micelles for Injection in Patients With Advanced Malignant Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: Docetaxel Polymeric Micelles for Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female aged 18 75 years old Patients with histopathologically or cytologically confirmed advanced or metastatic solid tumors who have failed or are not eligible for standard therapy in the past Have an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 There are measurable tumors(RECIST 1.1) Exclusion Criteria: Previous palliative chemotherapy with docetaxel failed Central nervous system metastasis or meningeal metastasis with clinical symptoms Has a history of serious cardiovascular disease A history of immunodeficiency, including a positive test for human immunodeficiency virus (HIV) Active hepatitis B (HBsAg positive, HBV DNA>; ULN) or hepatitis C (HCV antibody positive and HCV RNA>ULN) Has a history of allergies to yew medications Pregnant or lactating women The investigator considered that there were other reasons for the subjects' ineligibility for this clinical 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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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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Docetaxel Polymeric Micelles for Injection<br>Docetaxel Polymeric Micelles for Injection | Drug: Docetaxel Polymeric Micelles for Injection<br>* Docetaxel polymeric micelles，usage and quantity of Docetaxel polymeric micelles follows the clinical study proctol，not published.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose confirmation stage: Safety and tolerability to determine the subsequent recommended dosing regimen | Incidence of DLT（Dose limited toxicity） | 2 years | 
| Expansion stage: effect，ORR(Objective Response Rate ) by investigator | Proportion of subjects who have a complete or partial response relative to baseline as assessed by investigator according to RECIST 1.1 criteria | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose confirmation stage: Objective Response Rate（ORR） by investigator | Proportion of subjects who have a complete or partial response relative to baseline as assessed by investigator according to RECIST 1.1 criteria | 2 years | 
| Dose confirmation stage: Objective Response Rate（DoR）by investigator | Measured from the date of partial or complete response to therapy until the cancer progresses based on RECIST v1.1 criteria | 2 years | 
| Dose confirmation stage: Progression free survival（PFS） by investigator | PFS was defined as the time from the date of randomization to the first documented disease progression or death, whichever occurred first. Progression was based on tumor assessment according to the RECIST 1.1 criteria | 2 years | 
| Dose confirmation stage: Disease Control Rate（DCR）by investigator | Proportion of subjects who have a complete or partial response, or stable disease relative to baseline as assessed by investigator according to RECIST 1.1 criteria | 2 years | 
| Dose confirmation stage: Overall Survival（OS）by investigator | OS is the time interval from the date of randomization to death from any cause. | 2 years | 
| Dose confirmation stage: Area under the plasma concentration versus time curve（AUC） | Area under the plasma concentration versus time curve | Day 1 to Day 3 of Cycle 1，each cycle is 21 （queue A and C）or 28 days（queue B） | 
| Dose confirmation stage: Peak Plasma Concentration（Cmax） | Peak Plasma Concentration，Maximum concentration of HT001 derived from plasma concentration-time profile | Day 1 to Day 3 of Cycle 1，each cycle is 21 （queue A and C）or 28 days（queue B） | 
| Dose confirmation stage: Time to Peak（Tmax） | Time of peak blood concentration of HT001 derived from plasma concentration-time profile | Day 1 to Day 3 of Cycle 1，each cycle is 21 （queue A and C）or 28 days（queue B） | 
| Dose confirmation stage: Half-life（t1/2） | Half-life of HT001 derived from plasma concentration-time profile | Day 1 to Day 3 of Cycle 1，each cycle is 21 （queue A and C）or 28 days（queue B） | 
| Dose confirmation stage: Clearance（CL） | Clearance of HT001 derived from plasma concentration-time profile | Day 1 to Day 3 of Cycle 1，each cycle is 21 （queue A and C）or 28 days（queue B） | 
| Dose confirmation stage: Volume of distribution（Vd） | Volume of distribution of HT001 derived from plasma concentration-time profile | Day 1 to Day 3 of Cycle 1，each cycle is 21 （queue A and C）or 28 days（queue B） | 
| Dose confirmation stage: Mean Residence Time（MRT） | Mean Residence Time of HT001 derived from plasma concentration-time profile | Day 1 to Day 3 of Cycle 1，each cycle is 21 （queue A and C）or 28 days（queue B） | 
| Expansion stage: Objective Response Rate（DoR）by investigator | Measured from the date of partial or complete response to therapy until the cancer progresses based on RECIST v1.1 criteria | 2 years | 
| Expansion stage：Progression free survival（PFS） by investigator | PFS was defined as the time from the date of randomization to the first documented disease progression or death, whichever occurred first. Progression was based on tumor assessment according to the RECIST 1.1 criteria | 2 years | 
| Expansion stage：Disease Control Rate（DCR）by investigator | Proportion of subjects who have a complete or partial response, or stable disease relative to baseline as assessed by investigator according to RECIST 1.1 criteria | 1.5 year | 
| Expansion stage：Overall Survival（OS）by investigator | OS is the time interval from the date of randomization to death from any cause. | 2 years | 
| Expansion stage: The incidence and severity of adverse events (AEs) and serious adverse events (SAEs) | Frequency and severity of Adverse Events or Serious Adverse Events as defined by CTCAE version 5.0 | 2 years |