A Clinical Study of TQB3823 in Patients With Advanced Malignant Tumor
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: TQB3823 tablets 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. |
Drug: TQB3823 tablets
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.
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Outcome Measures
Primary Outcome Measures
- Dose Limiting Toxicities (DLT) [Baseline up to 28 days]
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.
- Maximum tolerated dose (MTD) [Baseline up to 28 days]
The highest dose at which no more than 33% of the subjects experience a dose-limiting toxicity (DLT) during treatment
Secondary Outcome Measures
- Adverse events (AEs) and serious adverse events (SAEs) [Baseline up to 28 days]
The occurrence of all AEs and SAEs，such as Anemia, Platelet count decreased, Nausea, Vomiting, Elevated transaminase.
- Overall response rate (ORR) [21 days]
Overall response rate（From the first drug treatment to the last drug treatment）
- Disease control rate（DCR） [21 days]
Disease control rate（From the first drug treatment to the last drug treatment）
- Progression-free survival (PFS) [21 days]
First-time progression of disease/ recurrence /death）
- Duration of Response (DOR) [21 days]
Baseline up to progression of disease/ recurrence /death
- Time to reach maximum (peak) plasma concentration following drug administration（Tmax） [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.]
To characterize the pharmacokinetics of TQB3823 by assessment of time to reach maximum plasma concentration after single and multiple dosing
- Maximum (peak) plasma drug concentration （Cmax） [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.]
Cmax is the maximum plasma concentration of TQB3823 or metabolite(s).
- Maximum (peak) steady-state plasma drug concentration during a dosage interval （Cmax,ss） [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.]
Cmax is the maximum plasma concentration of TQB3823 or metabolite(s).
- 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-∞） [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.]
To characterize the pharmacokinetics of TQB3823 by assessment of area under the plasma concentration time curve from the first dose to infinity.
- Apparent total clearance of the drug from plasma after oral administration （CL/f） [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.]
CL/f is total clearance rate for TQB3823.
- Elimination half-life（t1/2） [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.]
t1/2 is time it takes for the blood concentration of TQB3823 or metabolite(s) to drop by half.
- Mean residence time (MRT) [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.]
MRT describes the average time that TQB3823 or metabolite(s) remain in the body.
- Minimum steady-state plasma drug concentration during a dosage interval （Css-min） [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.]
Css-min is the minimum plasma concentration of TQB3823 or metabolite(s).
- Average steady-state plasma drug concentration during multiple-dose administration （Css-av） [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.]
Css-av is mean steady-state plasma concentration of TQB3823 or metabolite(s).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Subjects who voluntarily join the study, sign the informed consent form, and have good compliance.
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Aged from 18 to 75 years; Eastern Cooperative Oncology Group (ECOG) performance status score: 0-1; at least 3 months expected survival period.
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Subjects with relapse advanced malignant solid tumors clearly diagnosed by pathology and / or cytology, lack of conventional effective treatment methods.
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The function of main organs is normal.
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Subjects need to adopt effective methods of contraception.
Exclusion Criteria:
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Subjects with other malignancies currently or suffered within 3 years. The following two conditions can be enrolled: other malignant tumors treated with a single operation to achieve disease-free survival (DFS) for 5 consecutive years; cured cervical carcinoma in situ, non-melanoma skin cancer and superficial bladder tumors[ Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)].
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Subjects with multiple factors affecting oral administration.
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Subjets with unhealed toxicity above Grade 1 Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 due to previous antitumor treatment.
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Subjects who have received major surgical treatment, open biopsy or obvious traumatic injury within 28 days before first administration.
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Subjects with long lasting wounds or fractures.
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Subjects with a history of psychotropic drug abuse unable to quit or with mental disorders.
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Subjects with any severe and/or uncontrolled disease.
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Subjects who have received surgery, chemotherapy, radiotherapy or other anticancer therapies 4 weeks before the first administration ( 2 weeks for brain radiotherapy ).
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Subjects who have taken Chinese patent medicines with anti-tumor indications in the drug instructions that National Medical Products Administration (NMPA)approved within 2 weeks before the first administration.
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Subjects with pleural effusion, pericardial effusion or ascites that cannot be controlled and need repeated drainage.
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Subjects with known central nervous system metastases and/or cancerous meningitis.
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Subjects who have participated in other clinical studies within 4 weeks before the first administration.
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According to the judgment of the investigators, there are accompanying diseases that seriously endanger the safety of patients or affect the completion of the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sun Yat-sen University Cancer Cen | Guangzhou | Guangdong | China | 510060 |
Sponsors and Collaborators
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TQB3823-I-01