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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
126
HA132 will be administered intravenously (IV), once per 3 weeks.
Jilin Cancer Hospital
Changchun, Jilin, China
Incidence of Dose-limiting Toxicities (DLTs) in Stage I
Time frame: 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.
Time frame: From Baseline (Day 1) up to 28 days post last dose.
Maximum tolerated dose (MTD) in Stage I
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: Up to approximately 2 years.
PK Indicator: Area under plasma concentration vs time curve(AUC)、Peak plasma concentration(Cmax)、Terminal Half Life(T1/2).
Time frame: Day 1 of Cycle 1 up to Day 1 of Last Cycle.
ORR in Stage I
Time frame: Up to approximately 2 years.
Confirmed ORR in Stage I
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to approximately 2 years.
Incidence of Adverse Events and Serious Adverse Events (SAEs) in stage Ⅱ
Time frame: Up to approximately 2 years.
Estimated glomerular filtration rate (eGFR) and creatinine clearance
Time frame: Up to approximately 2 years.
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