A Study of Irinotecan Hydrochloride Liposome in Combination With 5-FU/LV in Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a dose-escalation and expansion, open label, single centre, phase Ib study. In this study, the tolerability, safety, pharmacokinetics and efficacy of irinotecan hydrochloride liposome injection in combination with 5-FU/LV were studied in patients with advanced solid tumors. Meanwhile, to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of irinotecan hydrochloride liposome.

Official Title
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A Phase Ib Study to Evaluate Tolerability, Safety and Pharmacokinetics of Irinotecan Hydrochloride Liposome Injection in Combination With 5-FU/LV in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: Irinotecan liposome、5-fluorouracil、Leucovorin


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 or active CNS metastasis; UGT1A1*28 homozygous mutants; 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

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 and expansion study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group:<br>Irinotecan liposome plus 5-fluorouracil, Leucovorin | Drug: Irinotecan liposome、5-fluorouracil、Leucovorin<br>* Irinotecan liposome、5-fluorouracil、Leucovorin<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 v4.03 | Assessed from study inclusion to 30 days after last dose | 
| Dose Limiting Toxicities (DLT) | Dose Limiting Toxicities for patients in combination treatment | DLTs will be evaluated during 28-day period following the first dose of study treatment | 
| Maximal tolerated dose (MTD) | Maximum tolerated dose for patients in combination 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 168 hours after the first dose | 
| Maximum observed plasma concentration (Cmax) | Cmax of total irinotecan, free irinotecan and SN-38 | up to 168 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 168 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 168 hours after the first dose | 
| Elimination half-life (T1/2) | T1/2 of total irinotecan, free irinotecan and SN-38 | up to 168 hours after the first dose | 
| Clearance of drug from plasma (CL) | CL of total irinotecan | up to 168 hours after the first dose | 
| Volume of distribution (Vss) | Vss of total irinotecan | up to 168 hours after the first dose |