Evaluation of the Safety and Efficacy of Albumin-bound Docetaxel

Study Overview
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Brief Summary
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This trial is an open-label, single-center, dose-escalation and cohort-expansion Phase I clinical study in patients with advanced solid tumors. The aim of this study is designed to evaluate the safety, tolerability, pharmacokinetics and preliminary antitumor activity of albumin-bound formulation of docetaxel for intravenous infusion in patients with advanced solid tumors.

Detailed Description
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This study was conducted in two stages. The first stage (Stage I) is a dose-escalation study. A classic 3+3 design will be used to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D). Patients with advanced solid tumors will be assigned to receive sequentially higher doses of albumin-bound formulation of docetaxel once every three weeks (a Cycle) by intravenous infusion, starting at a dose of 50mg/m2. Patients will receive the albumin-bound formulation of docetaxel

Official Title
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Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Albumin-bound Formulation of Docetaxel for Intravenous Infusion in Patients With Advanced Solid Tumors: A Phase 1, Single-center, Open-label, Dose-escalation Study

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: Albumin-bound docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18, ≤75 years, no gender limitation； Histologically or cytologically confirmed diagnosis of advanced or metastatic solid tumors, for which standard therapy either does not exist or has proven to be ineffective, intolerable or unacceptable for the patient； At least one measurable lesion as per RECIST version 1.1； Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1； Life expectancy ≥3 months； Adequate bone marrow, cardiac, liver and renal function； Exclusion Criteria: Chemotherapy, radiotherapy, biotherapy, endocrine therapy, targeted therapy, immunotherapy and other anti-tumor treatment within 4 weeks of the first dose of the study drug, 6 weeks for mitomycin C or nitrosoureas, 2 weeks (or 5 half-lives whichever is longer) for using fluorouracil or small molecule targeted drugs, 2 weeks for using traditional Chinese medicine with anti-tumor indications； Currently enrolled in any other clinical study, or administration of other investigational agents w

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: solid tumors<br>Albumin-bound docetaxel by intravenous infusion.Patients receive albumin-bound docetaxel once every three weeks (a Cycle), starting at a dose of 50mg/m2. | Drug: Albumin-bound docetaxel<br>* Albumin-bound docetaxel by intravenous infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who experienced AE during cycle1. | AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol specified procedure, whether or not considered related to the medicinal product/protocol specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. | 21 days. | 
| Number of participants who experienced DLT during cycle1. | A DLT was graded using the National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 4.02 and defined as any of the following: grade 3 or 4 non-hematologic adverse events unless they were not optimally treated with supportive care; grade 3 or 4 asymptomatic laboratory abnormal values lasting >7 days; prolonged grade 2 toxicity (lasting more than 2 weeks) leading to treatment interruption and/or dose reduction; pancytopenia with a hypocellular bone marrow and no marrow blasts lasting ≥6 weeks (AL participants); grade 3 neutropenia with fever or infection (OHM participants); grade 3 thrombocytopenia with bleeding (OHM participants); or grade 4 neutropenia or thrombocytopenia, regardless of symptoms and lasting ≥3 days (OHM participants). | 21 days. | 
| Classic 3+3 design to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) | The maximum tolerated dose (MTD) (if available) and recommended Phase 2 dose (RP2D) of Albumin-bound Docetaxel. | Through study completion, an average of 1 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve of Albumin-bound Docetaxel from time 0 to last (AUC 0-∞) | The pharmacokinetic parameters AUC0-last of Albumin-bound Docetaxel. | 21 days. | 
| Area under the concentration-time curve of Albumin-bound Docetaxel from time 0 to infinity (AUC 0-∞) | The pharmacokinetic parameters AUC0-∞ of Albumin-bound Docetaxel. | 21 days. | 
| Observed maximum concentration (Cmax )of Albumin-bound Docetaxel | The pharmacokinetic parameters Cmax of Albumin-bound Docetaxel. | 21 days. | 
| Time to maximum concentration (Tmax) of Albumin-bound Docetaxel | The pharmacokinetic parameters Tmax of Albumin-bound Docetaxel. | 21 days. | 
| Apparent terminal Half-Life (t1/2) of Albumin-bound Docetaxel | The pharmacokinetic parameters t½ of Albumin-bound Docetaxel. | 21 days. | 
| Apparent total body clearance (CL/F) of Albumin-bound Docetaxel | The pharmacokinetic parameters CL/F of Albumin-bound Docetaxel. | 21 days. | 
| Objective response rate (ORR) | Efficacy measures overall response rate (ORR) of Albumin-bound Docetaxel. | Through study completion, an average of 1 year. | 
| Progression free survival (PFS) | Efficacy measures progression-free survival (PFS) of Albumin-bound Docetaxel. | Through study completion, an average of 1 year. | 
| Disease control rate (DCR) | Efficacy measures disease control rate (DCR) of Albumin-bound Docetaxel. | Through study completion, an average of 1 year. | 
| Duration of response (DOR) | Efficacy measures duration of response (DOR) of Albumin-bound Docetaxel. | Through study completion, an average of 1 year. |