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This is a study to evaluate the maximum tolerated dose (MTD) , occurrence of all adverse events (AEs) and serious adverse events (SAEs) , pharmacokinetic parameters and antitumor effect of TQB3823 tablets in Chinese adult patients with advanced solid tumors .The study was divided into phase Ia and phase Ib, Phase Ia: Dose escalation period, to evaluate the safety and tolerability of TQB3823 tablets, determine MTD;Phase Ib: Effectiveness exploration period, to expand the safe and effective dose group, and to recommend appropriate dosage and method for subsequent clinical research.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TQB3823 tablets | Experimental | Subjects receive TQB3823 in the first cycle for a total of 28 days , a single dose on Day 1. Day 2 to Day 7 are the elution period, and the continuous doses are from Day 8 to Day 21. From the second cycle, continuous treatment for 28 days is as a treatment cycle. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TQB3823 tablets | Drug | TQB3823 is a small molecule Poly ADP-ribose Polymerase (PARP) inhibitor that can inhibit the enzyme activity of PARP1/2, making it difficult to repair the DNA in cancer cells, leading to cell death and delaying or blocking tumor development. |
| Measure | Description | Time Frame |
|---|---|---|
| Dose Limiting Toxicities (DLT) | Subjects within 28 days after treatment appear the following toxicity reaction relate to the drug :III °or above of non-hematological toxicity, IV°hematological toxicity ,Neutropenia associated with fever. | Baseline up to 28 days |
| Maximum tolerated dose (MTD) | The highest dose at which no more than 33% of the subjects experience a dose-limiting toxicity (DLT) during treatment | Baseline up to 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse events (AEs) and serious adverse events (SAEs) | The occurrence of all AEs and SAEs,such as Anemia, Platelet count decreased, Nausea, Vomiting, Elevated transaminase. | Baseline up to 28 days |
| Overall response rate (ORR) |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sun Yat-sen University Cancer Cen | Guangzhou | Guangdong | 510060 | China |
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Overall response rate(From the first drug treatment to the last drug treatment)
| 21 days |
| Disease control rate(DCR) | Disease control rate(From the first drug treatment to the last drug treatment) | 21 days |
| Progression-free survival (PFS) | First-time progression of disease/ recurrence /death) | 21 days |
| Duration of Response (DOR) | Baseline up to progression of disease/ recurrence /death | 21 days |
| Time to reach maximum (peak) plasma concentration following drug administration(Tmax) | To characterize the pharmacokinetics of TQB3823 by assessment of time to reach maximum plasma concentration after single and multiple dosing | Hour 0 (pre-dose), 1, 2, 3, 4, 6, 8, 11, 24, 48, 72, 120, 168 hours post-dose on single dose; Hour 0(pre-dose) of day 7,day 14 on multiple dose and Hour 0 (pre-dose), 1, 2, 3, 4, 6, 8, 11, 24 hours post-dose on multiple dose of day 21. |
| Maximum (peak) plasma drug concentration (Cmax) | Cmax is the maximum plasma concentration of TQB3823 or metabolite(s). | Hour 0 (pre-dose), 1, 2, 3, 4, 6, 8, 11, 24, 48, 72, 120, 168 hours post-dose on single dose; Hour 0(pre-dose) of day 7,day 14 on multiple dose and Hour 0 (pre-dose), 1, 2, 3, 4, 6, 8, 11, 24 hours post-dose on multiple dose of day 21. |
| Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss) | Cmax is the maximum plasma concentration of TQB3823 or metabolite(s). | Hour 0 (pre-dose), 1, 2, 3, 4, 6, 8, 11, 24, 48, 72, 120, 168 hours post-dose on single dose; Hour 0(pre-dose) of day 7,day 14 on multiple dose and Hour 0 (pre-dose), 1, 2, 3, 4, 6, 8, 11, 24 hours post-dose on multiple dose of day 21. |
| Area under the plasma concentration-time curve from time zero to time t (AUC0-t)、Area under the plasma concentration-time curve from time zero to infinity (ACU0-∞) | To characterize the pharmacokinetics of TQB3823 by assessment of area under the plasma concentration time curve from the first dose to infinity. | Hour 0 (pre-dose), 1, 2, 3, 4, 6, 8, 11, 24, 48, 72, 120, 168 hours post-dose on single dose; Hour 0(pre-dose) of day 7,day 14 on multiple dose and Hour 0 (pre-dose), 1, 2, 3, 4, 6, 8, 11, 24 hours post-dose on multiple dose of day 21. |
| Apparent total clearance of the drug from plasma after oral administration (CL/f) | CL/f is total clearance rate for TQB3823. | Hour 0 (pre-dose), 1, 2, 3, 4, 6, 8, 11, 24, 48, 72, 120, 168 hours post-dose on single dose; Hour 0(pre-dose) of day 7,day 14 on multiple dose and Hour 0 (pre-dose), 1, 2, 3, 4, 6, 8, 11, 24 hours post-dose on multiple dose of day 21. |
| Elimination half-life(t1/2) | t1/2 is time it takes for the blood concentration of TQB3823 or metabolite(s) to drop by half. | Hour 0 (pre-dose), 1, 2, 3, 4, 6, 8, 11, 24, 48, 72, 120, 168 hours post-dose on single dose; Hour 0(pre-dose) of day 7,day 14 on multiple dose and Hour 0 (pre-dose), 1, 2, 3, 4, 6, 8, 11, 24 hours post-dose on multiple dose of day 21. |
| Mean residence time (MRT) | MRT describes the average time that TQB3823 or metabolite(s) remain in the body. | Hour 0 (pre-dose), 1, 2, 3, 4, 6, 8, 11, 24, 48, 72, 120, 168 hours post-dose on single dose; Hour 0(pre-dose) of day 7,day 14 on multiple dose and Hour 0 (pre-dose), 1, 2, 3, 4, 6, 8, 11, 24 hours post-dose on multiple dose of day 21. |
| Minimum steady-state plasma drug concentration during a dosage interval (Css-min) | Css-min is the minimum plasma concentration of TQB3823 or metabolite(s). | Hour 0 (pre-dose), 1, 2, 3, 4, 6, 8, 11, 24, 48, 72, 120, 168 hours post-dose on single dose; Hour 0(pre-dose) of day 7,day 14 on multiple dose and Hour 0 (pre-dose), 1, 2, 3, 4, 6, 8, 11, 24 hours post-dose on multiple dose of day 21. |
| Average steady-state plasma drug concentration during multiple-dose administration (Css-av) | Css-av is mean steady-state plasma concentration of TQB3823 or metabolite(s). | Hour 0 (pre-dose), 1, 2, 3, 4, 6, 8, 11, 24, 48, 72, 120, 168 hours post-dose on single dose; Hour 0(pre-dose) of day 7,day 14 on multiple dose and Hour 0 (pre-dose), 1, 2, 3, 4, 6, 8, 11, 24 hours post-dose on multiple dose of day 21. |