A Study of Irinotecan Hydrochloride Liposome in Advanced Solid Tumors

Study Overview
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Brief Summary
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This is an open label, dose-escalation and expansion, single centre, phase Ia study . In this study, the tolerability, safety, pharmacokinetics and efficacy of irinotecan hydrochloride liposome injection were studied in patients with advanced solid tumors, to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of irinotecan hydrochloride liposome.

Official Title
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A Phase Ia Study on Tolerability and Pharmacokinetics of Irinotecan Hydrochloride Liposome Alone in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: Irinotecan liposome


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed solid tumors documented as advanced or metastatic disease; Subjects must be considered relapsed or refractory to standard therapies, have been intolerant to standard therapies, or have refused standard therapy; ECOG: 0-1; Adequate organ and bone marrow function; sign an informed consent. Exclusion Criteria: Patients with brain malignant tumor, lymphoma or other malignant hematologic diseases; Active CNS metastasis; Clinically significant GI disorders; Significant cardiovascular disease; Active infection or uncontrolled fever; Pregnant or breast feeding patients; Allergic to a drug ingredient or component; The investigators determined that other conditions were inappropriate for participation in this clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Interventional Model Description: A dose-escalation（3+3 design） and expansion study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group A<br>Treatment group : Irinotecan liposome | Drug: Irinotecan liposome<br>* Irinotecan liposome<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Event (AE) | Assessed by CTCAE 4.03 | Assessed from study inclusion to 30 days after last dose | 
| Dose Limiting Toxicities (DLT) | Dose limiting toxicities for patients in the treatment | DLTs will be evaluated during 21-day period following the first dose of study treatment | 
| Maximal tolerated dose (MTD) | Maximum tolerated dose for patients in the treatment | after the last patient in each cohort up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Objective response rate was based on response evaluation criteria in solid tumors 1.1 (RECIST 1.1) | maximum time on study 12 months | 
| Progression Free Survival | Progression-free survival was defined as the time from the date of randomization to the date of disease progression, or death (any cause) on or prior to the clinical cutoff date, whichever occurs first. | The maximum time in follow up was 12 months | 
| Time to reach maximum plasma concentration (Tmax) | Tmax of total irinotecan, free irinotecan and SN-38 | up to 120 hours after the first dose | 
| Maximum observed plasma concentration (Cmax) | Cmax of total irinotecan, free irinotecan and SN-38 | up to 120 hours after the first dose | 
| Area under the plasma concentration versus time curve from time zero to time of last observed concentration (AUC0-t) | AUC0-t of total irinotecan, free irinotecan and SN-38 | up to 120 hours after the first dose | 
| Area under the plasma concentration versus time curve from time zero to infinity (AUC0-inf) | AUC0-inf of total irinotecan, free irinotecan and SN-38 | up to 120 hours after the first dose | 
| Elimination half-life (T1/2) | T1/2 of total irinotecan, free irinotecan and SN-38 | up to 120 hours after the first dose | 
| Clearance of drug from plasma (CL) | CL of total irinotecan | up to 120 hours after the first dose | 
| Volume of distribution (Vss) | Vss of total irinotecan | up to 120 hours after the first dose |