A Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Efficacy of Cisplatin Micelle Injection (HA132) in Patients With Advanced Malignant Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- Cisplatin micelle injection (HA132)
- Conditions
- Advanced Malignant Solid Tumors
- Sponsor
- CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
- Enrollment
- 126
- Locations
- 1
- Primary Endpoint
- Confirmed objective response rate (ORR) in stage Ⅱ
- Status
- Not yet recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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:
- •Neutrophil absolute value (ANC) ≥ 1.5 × 10\^9/L;
- •Platelet (PLT) ≥ 90× 10\^9/L;
- •Hemoglobin (HB) ≥ 90 g/L;
Exclusion Criteria
- •The patient has received chemotherapy, biological therapy, endocrine therapy, targeted therapy, immunotherapy and other anti-tumor treatments or participated in other clinical trials within 4 weeks before the first use of the study drug, or within 5 half-lives of the treatment drug, whichever is longer;
- •The patient has received platinum-based therapy within 3 months prior to the study drug;
- •The patient has undergone major organ surgery (excluding needle biopsy) or suffered significant trauma within 4 weeks before the first use of the study drug;
- •The patient has received nephrotoxic or ototoxic drugs such as cephalosporin, aminoglycoside antibiotics, amphotericin B within 14 days before the first use of the study drug;
- •Those who are allergic to any excipients of the study drug or cisplatin and other platinum-based drug or have a history of severe allergies;
- •Any unresolved toxicities from prior anti-tumor therapy (including radiotherapy) greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1(except for alopecia or other adverse reactions judged no safety risk by the investigators);
- •Patients with clinical symptoms of central nervous system metastases or meningeal metastases, or there is other evidence that the patient's central nervous system metastases or meningeal metastases have not been controlled, and the investigators judge that they are not suitable for enrollment;
- •The patient has active infectious disease;
- •The patient has a history of autoimmune disease, immunodeficiency, including positive HIV test, or has other acquired, congenital immunodeficiency diseases, or a history of organ transplantation;
- •Active hepatitis B (hepatitis B virus titer \> 1000 copies/mL or 200 IU/mL), prophylactic antiviral therapy other than interferon is allowed; hepatitis C virus infection;
Arms & Interventions
Cisplatin micelle injection (HA132)
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).
Intervention: Cisplatin micelle injection (HA132)
Outcomes
Primary Outcomes
Confirmed objective response rate (ORR) in stage Ⅱ
Time Frame: Up to approximately 2 years.
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).
Incidence of Dose-limiting Toxicities (DLTs) 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
Time Frame: Day 1 to 21 of Cycle 1 (each cycle of 21 days).
The RP2D will be determined based on safety data including DLT, preliminary efficacy data,and PK data.
Incidence of adverse events in Stage I
Time Frame: From Baseline (Day 1) up to 28 days post last dose.
Patients will be assessed for incidence and severity of adverse events(AEs) according to NCI-CTCAE criteria.
Maximum tolerated dose (MTD) in Stage I
Time Frame: Day 1 to 21 of Cycle 1 (each cycle of 21 days).
Objective Response Rate (ORR) in stage Ⅱ
Time Frame: Up to approximately 2 years.
Proportion of patients whose best overall response is CR or PR in studies assessed according to RECIST v1.1.
Secondary Outcomes
- 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.)
- Confirmed ORR in Stage I(Up to approximately 2 years.)
- Duration of response (DOR)(Up to approximately 2 years.)
- ORR in Stage I(Up to approximately 2 years.)
- Progression-free survival (PFS)(Up to approximately 2 years.)
- Disease control rate (DCR)(Up to approximately 2 years.)
- Estimated glomerular filtration rate (eGFR) and creatinine clearance(Up to approximately 2 years.)
- Incidence of Adverse Events and Serious Adverse Events (SAEs) in stage Ⅱ(Up to approximately 2 years.)