Clinical trial NCT04275050: A Study to Evaluate the Tolerance and Pharmacokinetics of TQB3303 Tablets
Official title: A Phase I, Open-label, Dose Escalation and Expansion Study to Evaluate the Tolerance and Pharmacokinetics of TQB3303 Tablets
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Malignant Solid Tumor
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-02-19
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: TQB3303 tablet is a small molecule oral drug inhibiting cyclin-dependent kinases 4 and 6 (CDK4 / 6). Based on current research, overexpression of positive regulatory proteins in the cell cycle is one of the important reasons for resistance to endocrine therapy. CDK4 / 6 is the key regulators of the cell cycle inhibiting tumor cell proliferation.


Eligibility criteria: Inclusion Criteria:

* 1.≥ 18 years old. 2. Histologically or cytologically confirmed advanced malignant solid tumors, without conventional treatment methods or fail or relapse after treatment.

  3.Has at least one measurable lesion (based on RECIST 1.1) or bone metastases. 4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2; Life expectancy ≥12 weeks.

  5. Adequate organ system function. 6.Understood and signed an informed consent form. 7. Male or female subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study (such as intrauterine devices , contraceptives or condoms) ；No pregnant or breastfeeding women, and a negative pregnancy test are received within 7 days before the randomization.

Exclusion Criteria:

* 1. Has diagnosed and/or treated additional malignancy with the exception of cured basal cell carcinoma of the skin and cervical carcinoma in situ.

  2. Has received cytotoxic chemotherapy in 4 weeks, or mitomycin C or nitrosourea in 6 weeks.

  3. Has received any anti-tumor treatment such as hormone therapy, radioimmunotherapy, molecular targeted therapy, immunotherapy or other biological therapy within 4 weeks.

  4. Has received other CDK4 / 6 inhibitors. 5. Has known spinal cord compression, cancerous meningitis, newly diagnosed central nervous system metastasis or brain metastases with stable symptoms less than 4 weeks; asymptomatic and stable imaging without corticosteroid treatment.

  6.Has received stem cell or bone marrow transplant. 7.Has multiple factors affecting oral medication. 8.Has uncured wounds or fracture, except of pathological fracture with bone metastases patients.

  9.Has uncontrolled cardiovascular disease. 10.Has received CYP3A4 inhibitors or inducers during the screening period and during the trial.

  11.Has drug abuse history that unable to abstain from or mental disorders. 12.urinary protein ≥ ++, and the 24-hour urine protein quantification \> 1.0 g. 13. Has active hepatitis B or C. 14. Has a history of autoimmune disease, immunodeficiency. 15. Hypersensitivity to TQB3303 or its excipient. 16. Has participated in other clinical trials within 4 weeks before participating in this trial.

  17. According to the judgement of the researchers, there are other factors that subjects are not suitable for the study.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: Baseline up to 28 days
Secondary outcomes:
measure: Cmax
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 11, 24, 48, 72, 120 hours post-dose on single dose; Hour 0 of day 7,day 14,day21 on multiple dose and hour 0, 0.5, 1, 2, 3, 4, 6, 8, 11, 24, 48, 72, 120 hours post-dose on multiple dose of day 28.
measure: Tmax
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 11, 24, 48, 72, 120 hours post-dose on single dose; Hour 0 of day 7,day 14,day21 on multiple dose and hour 0, 0.5, 1, 2, 3, 4, 6, 8, 11, 24, 48, 72, 120 hours post-dose on multiple dose of day 28.
measure: AUC0-t
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 11, 24, 48, 72, 120 hours post-dose on single dose; Hour 0 of day 7, day 14, day21 on multiple dose and hour 0, 0.5, 1, 2, 3, 4, 6, 8, 11, 24, 48, 72, 120 hours post-dose on multiple dose of day 28.
measure: Overall response rate (ORR)
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
measure: Progression-free survival (PFS)
timeFrame: up to 96 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese Academy of Medical Sciencesand Peking Union Medical College
state: Beijing
Study officials:
References: