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This is a multicenter, open-label, dose-escalation, dose-expansion, and cohort-expansion Phase I/II clinical study to evaluate safety, tolerability, pharmacokinetics, antitumor efficacy and to determine the maximum tolerated dose (MTD) and recommended Phase 2 doses (RP2D) of cisplatin micelle injection in patients with advanced malignant solid tumors. This study is divided into two stages, the first stage (stage I) is the dose escalation and dose expansion study of cisplatin micelle injection, to determine the maximum tolerated dose (MTD), and to initially explore the recommended dose of phase II clinical practice (RP2D). The second stage (stage II) is the cisplatin micelle injection cohort expansion study to evaluate the efficacy and safety of cisplatin micelle injection (HA132) in patients with advanced solid tumors.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cisplatin micelle injection (HA132) | Experimental | Dose-escalation: Five dose levels have been selected for evaluation in the Phase Ⅰ of the study. Dose escalation decisions will be determined based on toxicities observed during the first cycle. Dose-expansion: Patients will be administered HA132 at one or two dose levels (e.g. MTD and the dose below MTD). Cohort-expansion: Patients will be administered HA132 at one or two dose levels (e.g. MTD and the dose below MTD). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cisplatin micelle injection (HA132) | Drug | HA132 will be administered intravenously (IV), once per 3 weeks. |
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| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Dose-limiting Toxicities (DLTs) in Stage I | Day 1 to 21 of Cycle 1 (each cycle of 21 days). | |
| Incidence of adverse events in Stage I | Patients will be assessed for incidence and severity of adverse events(AEs) according to NCI-CTCAE criteria. | From Baseline (Day 1) up to 28 days post last dose. |
| Maximum tolerated dose (MTD) in Stage I | Day 1 to 21 of Cycle 1 (each cycle of 21 days). | |
| Recommended phase 2 dose (RP2D) in Stage I | The RP2D will be determined based on safety data including DLT, preliminary efficacy data,and PK data. | Day 1 to 21 of Cycle 1 (each cycle of 21 days). |
| Objective Response Rate (ORR) in stage Ⅱ | Proportion of patients whose best overall response is CR or PR in studies assessed according to RECIST v1.1. | Up to approximately 2 years. |
| Confirmed objective response rate (ORR) in stage Ⅱ | During the study period, the best overall response is the proportion of patients with confirmed CR or PR (ie, CR+PR) as assessed by Response Evaluation Criteria in Solid Tumors.(RECIST v1.1). | Up to approximately 2 years. |
| Measure | Description | Time Frame |
|---|---|---|
| PK Indicator: Area under plasma concentration vs time curve(AUC)、Peak plasma concentration(Cmax)、Terminal Half Life(T1/2). | Day 1 of Cycle 1 up to Day 1 of Last Cycle. | |
| ORR in Stage I | Up to approximately 2 years. |
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Inclusion Criteria:
Aged 18 to 70 years (inclusive), no gender limitation;
Stage I: patients with advanced, recurrent or metastatic solid tumors confirmed by histology or cytology, and no standard treatment, or ineffective or intolerable to standard treatment, or those who are not eligible to receive standard treatment; Stage II: Pending;
Have at least one measurable lesion according to RECIST v1.1;
Eastern Cooperative Oncology Group (ECOG) physical performance status score of 0-1;
Life expectancy of at least 3 months;
Major organ function within 7 days prior to treatment, meeting the following criteria (have not received blood transfusion, EPO, G-CSF or other medical supportive treatment within 14 days before study drug administration):
Blood routine:
Renal function:
Liver function:
Women of childbearing age should agree that contraceptive measures (such as intrauterine device or condoms) must be used within study period and within 6 months after the end of the study; the serum or urine pregnancy tests is negative within 7days prior to the study for non-lactating patients; men should agree to use contraceptive measures during the study period and within 6 months after the end of the study period;
Patients must give informed consent to this study before the trial, and voluntarily sign the written informed consent.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xianying Piao, doctor | Contact | +86-17813168890 | piaoxianying@mail.ecspc.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Jilin Cancer Hospital | Changchun | Jilin | 130000 | China |
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| Confirmed ORR in Stage I | Up to approximately 2 years. |
| Progression-free survival (PFS) | Progression-free survival is defined as the time from the patient's first dose of study treatment (HA132) to the first date of either disease progression or death, whichever occurs first. | Up to approximately 2 years. |
| Disease control rate (DCR) | Proportion of patients whose best overall response is CR, PR or SD in studies assessed according to RECIST v1.1. | Up to approximately 2 years. |
| Duration of response (DOR) | The DOR for a responder is defined as the time from the patient's initial objective response to the first date of either disease progression or death, whichever occurs first. | Up to approximately 2 years. |
| Incidence of Adverse Events and Serious Adverse Events (SAEs) in stage Ⅱ | Up to approximately 2 years. |
| Estimated glomerular filtration rate (eGFR) and creatinine clearance | Up to approximately 2 years. |