Advanced Solid Tumors
Conditions
Brief summary
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.
Interventions
Irinotecan liposome、5-fluorouracil、Leucovorin
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
a dose-escalation and expansion study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed solid tumors documented as advanced or metastatic disease; 2. Subjects must be considered relapsed or refractory to standard therapies, have been intolerant to standard therapies, or have refused standard therapy; 3. ECOG: 0-1; 4. Adequate organ and bone marrow function; 5. sign an informed consent.
Exclusion criteria
1. Patients with brain malignant tumor or active CNS metastasis; 2. UGT1A1\*28 homozygous mutants; 3. Clinically significant GI disorders; 4. Significant cardiovascular disease; 5. Active infection or uncontrolled fever; 6. Pregnant or breast feeding patients; 7. Allergic to a drug ingredient or component; 8. The investigators determined that other conditions were inappropriate for participation in this clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event (AE) | Assessed from study inclusion to 30 days after last dose | Assessed by CTCAE v4.03 |
| Dose Limiting Toxicities (DLT) | DLTs will be evaluated during 28-day period following the first dose of study treatment | Dose Limiting Toxicities for patients in combination treatment |
| Maximal tolerated dose (MTD) | after the last patient in each cohort up to 12 months | Maximum tolerated dose for patients in combination treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed plasma concentration (Cmax) | up to 168 hours after the first dose | Cmax of total irinotecan, free irinotecan and SN-38 |
| Area under the plasma concentration versus time curve from time zero to time of last observed concentration (AUC0-t) | up to 168 hours after the first dose | AUC0-t of total irinotecan, free irinotecan and SN-38 |
| Area under the plasma concentration versus time curve from time zero to infinity (AUC0-inf) | up to 168 hours after the first dose | AUC0-inf of total irinotecan, free irinotecan and SN-38 |
| Objective Response Rate | maximum time on study 12 months | Objective response rate was based on response evaluation criteria in solid tumors 1.1 (RECIST 1.1) |
| Clearance of drug from plasma (CL) | up to 168 hours after the first dose | CL of total irinotecan |
| Volume of distribution (Vss) | up to 168 hours after the first dose | Vss of total irinotecan |
| Elimination half-life (T1/2) | up to 168 hours after the first dose | T1/2 of total irinotecan, free irinotecan and SN-38 |
| Progression Free Survival | The maximum time in follow up was 12 months | 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. |
| Time to reach maximum plasma concentration (Tmax) | up to 168 hours after the first dose | Tmax of total irinotecan, free irinotecan and SN-38 |
Countries
China
Outcome results
None listed