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This is a Phase I, open-label, non-randomized, dose-escalation study to evaluate the safety and tolerability, the maximum tolerated dose (MTD) and the dose limited toxicity(DLT) of LY01610 monotherapy and combine with 5-Fu in patients with advanced solid tumors. Additionally, the pharmacokinetics and preliminary efficacy of LY01610 monotherapy and combine with 5-Fu will be investigated in this study.
This study will be conducted in two stages: In the first stage, ascending doses of LY01610 will be administered as monotherapy in participants with solid tumors. The starting dose was 30 mg/m2 and the subsequent dose was increased according to the protocol of 60 mg/m2, 90 mg/m2, 120 mg/m2, 150 mg/m2, 180mg/m2. Each subject received only one dose of the drug, and the next dose group study could only be performed if the previous dose group was completed 21 days of observation after the first dose and safe tolerance was confirmed. According to the subjects' tolerance, appropriate doses will be selected and the safety, PK characteristics and initial efficacy of LY01610 were further evaluated in additional 6 - 8 patients. The interval between the first dose and the second dose was 3 weeks, followed by 2 weeks.Another 8 subjects were enrolled and given CAMPTO® (180 mg/m2) once every 2 weeks to perform the pharmacokinetic profiles.
The second stage is a dose escalation study of LY01610 combined with 5-Fu. Based on the results of the first stage, three doses of low, medium and high doses were selected in combination with a fixed dose of 5-Fu to determine the DLT and MTD. Similarly, according to the subjects' tolerance, appropriate dose will be selected and the safety, PK characteristics and initial efficacy of LY01610 combined with a fixed dose of 5-Fu were further evaluated in 6 - 8 patients. The drug was administered every 2 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LY01610-Dose Escalation | Experimental | The starting dose was 30 mg/m2 IV and the subsequent dose was increased according to the protocol of 60 mg/m2, 90 mg/m2, 120 mg/m2, 150 mg/m2, 180mg/m2. The interval between the first dose and the second dose was 3 weeks, followed by 2 weeks. |
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| LY01610-Dose Extension | Experimental | According to the subjects' tolerance, appropriate dose will be selected and the safety, PK characteristics and initial efficacy of LY01610 were further evaluated in 6 - 8 patients. The interval between the first dose and the second dose was 3 weeks, followed by 2 weeks. |
|
| LY01610 with 5-Fu -Dose Escalation | Experimental | Dose Escalation: Based on the results of the first stage, three doses of low, medium and high doses were selected in combination with a fixed dose of 5-Fu to determine the DLT, MTD, PK characteristics and the preliminary efficacy. 5-Fu, 400mg/m2 will be administered intravenously on days 1, followed by 600 mg/m2 given as a 22-hour continuous infusion on day 1 and 2, every 2 weeks. |
|
| LY01610 with 5-Fu -Dose Extension | Experimental | Similarly, according to the subjects' tolerance, appropriate dose will be selected and the safety, PK characteristics and initial efficacy of LY01610 combined with a fixed dose of 5-Fu were further evaluated in additional 6 - 8 patients. In dose escalation and dose extension stages, both LY01610 and fixed dose 5-Fu will be given once every 2 weeks. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LY01610 ( Irinotecan hydrochloride liposome injection ) | Drug | Part1-Dose Escalation and Part1-Dose Extension : subjects take LY01610; |
|
| Measure | Description | Time Frame |
|---|---|---|
| Dose limiting toxicity (DLT) | The DLT of LY01610 monotherapy was obtained through the dose-increasing study of LY01610 | 21 days for the LY01610 monotherapy (first treatment cycle of every subjects) |
| Dose limiting toxicity (DLT) | The DLT of combination of LY01610 and 5-fu was obtained through the dose-increasing study of LY01610 and 5-Fu | 14 days for the LY01610 combined 5-Fu (first treatment cycle of every subjects) |
| Maximum tolerated dose(MTD) | The MTD of LY01610 monotherapy was obtained through the single-drug dose increase study | 21 days for the LY01610 monotherapy (first treatment cycle of every subjects) |
| Maximum tolerated dose(MTD) | The MTD of combination of LY01610 and 5-fu was obtained through the combined dose increase study | 14 days for the LY01610 combined 5-Fu (first treatment cycle of every subjects) |
| Measure | Description | Time Frame |
|---|---|---|
| AUC | The AUC of LY01610 monotherapy was obtained through the dose escalation and extension study，the AUC of active comparator CAMPTO® was obtained through the study，and the AUC of LY01610 combined with 5-fu was obtained through the dose escalation and extension study. | 22 days for the LY01610 monotherapy (first treatment cycle of every subjects)，5 days for the active comparator CAMPTO® (first treatment cycle of every subjects)，and 15 days for the LY01610 combined with 5-fu(first treatment cycle of every subjects) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Huang jing | Chinese Academy of Medical Sciences and Peking Union Medical College | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chinese Academy of Medical Sciences and Peking Union Medical College | Beijing | Beijing Municipality | 100021 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34031756 | Derived | Liu Y, Zhang B, Xu J, Wang X, Tang J, Huang J. Phase I study of liposomal irinotecan (LY01610) in patients with advanced esophageal squamous cell carcinoma. Cancer Chemother Pharmacol. 2021 Sep;88(3):403-414. doi: 10.1007/s00280-021-04294-2. Epub 2021 May 24. |
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Parallel
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None，Open Label
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| Hydrochloride Injection- pharmacokinetics comparative study | Active Comparator | After receiving the MTD of LY01610, another 8 subjects were enrolled and given Irinotecan Hydrochloride Injection（captol ®） (180mg/m2) once every 2 weeks. Upon completion of the pharmacokinetics study, the sponsor will continue to provide the study drug treatment free of charge, and the researcher will conduct treatment and examination according to the subject's situation, without collecting any safety and efficacy data of the subject. |
|
| LY01610 ( Irinotecan hydrochloride liposome injection ) with 5-Fu（Fluorouracil Injection） | Drug | Part2-Dose Escalation and Part2-Dose Extension : subjects take LY01610 with 5-Fu; |
|
| Irinotecan Hydrochloride Injection（CAMPTO®） | Drug | Irinotecan Hydrochloride Injection（CAMPTO®） pharmacokinetics comparative study |
|
| t1/2 | The t1/2 of LY01610 monotherapy was obtained through the dose escalation and extension study，the t1/2 of active comparator CAMPTO® was obtained through the study，and the t1/2 of LY01610 combined with 5-fu was obtained through the dose escalation and extension study. | 22 days for the LY01610 monotherapy (first treatment cycle of every subjects)，5 days for the active comparator CAMPTO® (first treatment cycle of every subjects)，and 15 days for the LY01610 combined with 5-fu(first treatment cycle of every subjects) |
| Cmax | The Cmax of LY01610 monotherapy was obtained through the dose escalation and extension study，the Cmax of active comparator CAMPTO® was obtained through the study，and the Cmax of LY01610 combined with 5-fu was obtained through the dose escalation and extension study. | 22 days for the LY01610 monotherapy (first treatment cycle of every subjects)，5 days for the active comparator CAMPTO® (first treatment cycle of every subjects)，and 15 days for the LY01610 combined with 5-fu(first treatment cycle of every subjects) |
| tmax | The tmax of LY01610 monotherapy was obtained through the dose escalation and extension study，the tmax of active comparator CAMPTO® was obtained through the study，and the tmax of LY01610 combined with 5-fu was obtained through the dose escalation and extension study. | 22 days for the LY01610 monotherapy (first treatment cycle of every subjects)，5 days for the active comparator CAMPTO® (first treatment cycle of every subjects)，and 15 days for the LY01610 combined with 5-fu(first treatment cycle of every subjects) |
| Vd | The Vd of LY01610 monotherapy was obtained through the dose escalation and extension study，the Vd of active comparator CAMPTO® was obtained through the study，and the Vd of LY01610 combined with 5-fu was obtained through the dose escalation and extension study. | 22 days for the LY01610 monotherapy (first treatment cycle of every subjects)，5 days for the active comparator CAMPTO® (first treatment cycle of every subjects)，and 15 days for the LY01610 combined with 5-fu(first treatment cycle of every subjects) |
| CL | The CL of LY01610 monotherapy was obtained through the dose escalation and extension study，the CL of active comparator CAMPTO® was obtained through the study，and the CL of LY01610 combined with 5-fu was obtained through the dose escalation and extension study. | 22 days for the LY01610 monotherapy (first treatment cycle of every subjects)，5 days for the active comparator CAMPTO® (first treatment cycle of every subjects)，and 15 days for the LY01610 combined with 5-fu(first treatment cycle of every subjects) |
| MRT | The MRT of LY01610 monotherapy was obtained through the dose escalation and extension study，the MRT of active comparator CAMPTO® was obtained through the study，and the MRT of LY01610 combined with 5-fu was obtained through the dose escalation and extension study. | 22 days for the LY01610 monotherapy (first treatment cycle of every subjects)，5 days for the active comparator CAMPTO® (first treatment cycle of every subjects)，and 15 days for the LY01610 combined with 5-fu(first treatment cycle of every subjects) |
| Kel | The Kel of LY01610 monotherapy was obtained through the dose escalation and extension study，the Kel of active comparator CAMPTO® was obtained through the study，and the Kel of LY01610 combined with 5-fu was obtained through the dose escalation and extension study. | 22 days for the LY01610 monotherapy (first treatment cycle of every subjects)，5 days for the active comparator CAMPTO® (first treatment cycle of every subjects)，and 15 days for the LY01610 combined with 5-fu(first treatment cycle of every subjects) |
| Best Objective Response Rate | Preliminary efficacy evaluation of LY01610 and LY01610 combined with 5-fu | 8 weeks from enrollment |
| Progression Free Survival | Preliminary efficacy evaluation of LY01610 and LY01610 combined with 5-fu | from the date of enrollment to the date of disease progression or death up to 24 months from randomisation of the subject |
| Overall Survival | Preliminary efficacy evaluation of LY01610 and LY01610 combined with 5-fu | from the date of enrollment to the date of death up to 24 months from randomisation of the subject |