Clinical trial NCT05046847: A Clinical Study to Evaluate the Tolerability and Pharmacokinetics of TQB3811 Tablets in Patients With Advanced Malignant Tumors
Official title: Phase I Clinical Study to Evaluate the Tolerability and Pharmacokinetics of TQB3811 Tablets in Patients With Advanced Malignant Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Solid Tumor
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-09-16
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: TQB3811 tablet is a second-generation tropomyosin receptor kinase (TRK) inhibitor that selectively inhibits the kinase activity of TRKA, TRKB, and TRKC, and also selectively inhibits the kinase activity of TRKA, TRKB, and TRKC that produce secondary drug-resistant mutations.


Eligibility criteria: Inclusion Criteria:

* Patients with advanced malignancy diagnosed histologically and/or cytologically, who have failed standard treatment or are unable to receive standard treatment or have no effective treatment.
* Age: 18\~75 years old.
* Women of childbearing age must be negative for serum or urine HCG within 7 days prior to study enrollment and must be non-lactating; Patients should agree to use contraception during the study period and for 6 months after the study period.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; Life expectancy ≥ 3 months.
* Patients voluntarily joined the study and signed the informed consent, showing good compliance.

Exclusion Criteria:

* Patients has had or is currently having other malignant tumors within 3 years.
* Patients have multiple factors that affect their oral medication (such as inability to swallow, chronic diarrhea, and intestinal obstruction).
* The patient had unmitigated toxic reactions due to any prior treatment.
* Patients underwent major surgical treatment, open biopsy, or significant traumatic injury within 4 weeks prior to the start of study treatment.
* Patients have long-term unhealed wounds or fractures.
* The patient had experienced an arterial/venous thrombosis event in the past 6 months, such as a cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep venous thrombosis, and pulmonary embolism.
* The patient has a history of psychotropic drug abuse and cannot quit or has mental disorders.
* Patients are taking cytochrome P450 3A (CYP3A) inhibitors or inducers.
* Patients have uncontrolled pleural effusion, pericardial effusion, or ascites that still require repeated drainage.
* Patients with brain metastases with symptoms or control of symptoms for less than 2 weeks.
* The patients were currently breastfeeding or planned to breastfeed during the study period.
* Patients who, in the investigator's judgment, have a comorbidity that seriously endangers patient safety or interferes with study completion, or who are considered unsuitable for inclusion for other reasons

Primary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: Baseline up to 32 weeks
measure: Adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Baseline up to 28 days
measure: Dose-limiting toxicity (DLT)
timeFrame: Baseline up to 32 weeks
Secondary outcomes:
measure: Time to reach maximum (peak) plasma concentration following drug administration（Tmax）
timeFrame: 15, 30minutes, 1, 2, 4, 6, 8,10, 24, 48 hours after oral administration of day 1 and day 11;30 minutes before oral administration on day 1, day5, day7,day8 ,day 9 and day11.
measure: Maximum (peak) plasma drug concentration （Cmax）
timeFrame: 15, 30 minutes, 1, 2, 4, 6, 8,10, 24, 48 hours after oral administration of day 1 ;30 minutes before oral administration on day 1.
measure: Elimination half-life （t1/2）
timeFrame: 15, 30minutes, 1, 2, 4, 6, 8,10, 24, 48 hours after oral administration of day 1 and day 11;30 minutes before oral administration on day 1, day5, day7,day8 ,day 9 and day11.
measure: Area under the plasma concentration-time curve from time zero to time t （AUC0-t）
timeFrame: 15, 30 minutes, 1, 2, 4, 6, 8,10, 24, 48 hours after oral administration of day 1 ;30 minutes before oral administration on day 1.
measure: Maximum (peak) steady-state plasma drug concentration during a dosage interval （Cmax,ss）
timeFrame: 15, 30 minutes, 1, 2, 4, 6, 8,10, 24, 48 hours after oral administration of day 1 and day 11;30 minutes before oral administration on day 1, day5, day7,day8 ,day 9 and day11.
measure: Minimum steady-state plasma drug concentration during a dosage interval （Css-min）
timeFrame: 15, 30 minutes, 1, 2, 4, 6, 8,10, 24, 48 hours after oral administration of day 1 and day 11;30 minutes before oral administration on day 1, day5, day7,day8 ,day 9 and day11.
measure: Concentration at the end of the dosing interval (AUCtau,ss)
timeFrame: 15, 30 minutes, 1, 2, 4, 6, 8,10, 24, 48 hours after oral administration of day 1 and day 11;30 minutes before oral administration on day 1, day5, day7,day8 ,day 9 and day11.
measure: Progress Free Survival（PFS）
timeFrame: up to 96 weeks
measure: Disease control rate（DCR）
timeFrame: up to 96 weeks
measure: Duration of Response (DOR)
timeFrame: up to 96 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
References: