A Clinical Study of TQB3823 in Patients With Advanced Malignant Tumor
- Conditions
- Advanced Solid Tumor
- Interventions
- Drug: TQB3823 tablets
- Registration Number
- NCT05021367
- Lead Sponsor
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 164
- Subjects who voluntarily join the study, sign the informed consent form, and have good compliance.
- Aged from 18 to 75 years; Eastern Cooperative Oncology Group (ECOG) performance status score: 0-1; at least 3 months expected survival period.
- Subjects with relapse advanced malignant solid tumors clearly diagnosed by pathology and / or cytology, lack of conventional effective treatment methods.
- The function of main organs is normal.
- Subjects need to adopt effective methods of contraception.
- 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)].
- Subjects with multiple factors affecting oral administration.
- Subjets with unhealed toxicity above Grade 1 Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 due to previous antitumor treatment.
- Subjects who have received major surgical treatment, open biopsy or obvious traumatic injury within 28 days before first administration.
- Subjects with long lasting wounds or fractures.
- Subjects with a history of psychotropic drug abuse unable to quit or with mental disorders.
- Subjects with any severe and/or uncontrolled disease.
- Subjects who have received surgery, chemotherapy, radiotherapy or other anticancer therapies 4 weeks before the first administration ( 2 weeks for brain radiotherapy ).
- 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.
- Subjects with pleural effusion, pericardial effusion or ascites that cannot be controlled and need repeated drainage.
- Subjects with known central nervous system metastases and/or cancerous meningitis.
- Subjects who have participated in other clinical studies within 4 weeks before the first administration.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description TQB3823 tablets 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.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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）
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
Progression-free survival (PFS) 21 days First-time progression of disease/ recurrence /death）
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).
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.
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).
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.
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.
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).
Trial Locations
- Locations (1)
Sun Yat-sen University Cancer Cen
🇨🇳Guangzhou, Guangdong, China