A Phase I Study of TQB3616 on Tolerance and Pharmacokinetics

Study Overview
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Brief Summary
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TQB3616 may work in cancer by stopping cancer cells from multiplying.TQB3616 is in a new class of drugs called CDK inhibitors.This research study is the first time that TQB3616 will be given to people.TQB3616 is taken by mouth daily.

Official Title
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A Phase I Clinical， Tolerance and Pharmacokinetic Evaluation of 1 Schedules of Oral TQB3616，A Cyclin-Dependent Kinase Inhibitor ，In Patients With Advanced Breast Cancer

Conditions
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Advanced Breast Cancer

Intervention / Treatment
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* Drug: TQB3616


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years old Patients definitely diagnosed by pathology and/or cytology as advanced breast cancer with ER+、Her2-,who failed with standard endocrine therapy. ECOG PS:0-1,Survival is expected to be greater than 3 months Main organs function is normal or must meet the following criteria(within past 14 days) 1) hemoglobin≥90g/L; neutrophils≥1.5 x109/L; Platelets≥100 x109/L 2)Albumin≥29g/L; total bilirubin ≤ 1.5 x upper limit of normal (ULN); aspartic transaminase(AST) and alanine transaminase(ALT)≤2.5 ULN, and ≤ 5 x ULN with hepatic metastasis;serum creatinine ≤1.5 xULN，creatinine clearance >60ml/min; Triglyceride≤3.0mmol/L, cholesterol≤7.75mmol/L 3)Doppler ultrasound evaluation: Left ventricular ejection fraction(LVEF)≥50% 5.Patients should be voluntary and sign the informed consent before taking part in the study Exclusion Criteria: Patients with malignant tumors, except for Cured cutaneous basal cell carcinoma and cervical carcinoma in situ Prior treatment with chemotherapy with cytotoxic drugs within 4 weeks, mitomycin C or nirtosocarbamide within 8 weeks Prior treatment with any anti-cancer therapy including hormone therapy radioimmunotherapy, molecular targeted therapy, immunotherapy or other biological therapy with 2 weeks Patients treated with other CDK4/6 inhibitors; Patients with brain metastasis, spinal cord compression, cancerous meningitis, CT or MRI examination reminds patients with cerebral or soft meningeal diseases in the screening phase; Previous history of stem cell or bowe marrow transplant; A variety of factors that affect oral medication (such as inability to swallow, gastrointestinal resection, intestinal obstruction, etc.) Patients with non-healing wounds or fractures, except for bone metastatics with pathologic frature Previous history of uncontrolled cardiovascular disease including: a) Grade 3 or higher congestive heart failure (NYHA Classification);b)unstable angina pectoris or newly developped angina pectoris within 3months before the trial; c) Myocardial in farction or stroke occured within 6 months prior to intiation of trial; d) Arrhythmias requiring antiarrhythmic treatment(beta-blocker or digoxin is permitted) Patients who need to take CYP3A4 inhibitors or inducers from the screening period; Patients with drug abuse history or unable to get rid of drugs or Patients with mental disorders Patients with the urine protein≥2+, total ammount of 24 hours urinary protein determination>1.0 grams; Patients with hyperactive/venous thrombosis events within 6 months,such as cerebrovascular accidents (including temporary ischemic attack), deep venous thrombosis and pulmonary embolism Patients with active hepatitis b or c infection Patients with immunodeficiency, including HIV positive or other acquired, congenital immunodeficiency disease, or organ transplant history; Patients allergic to TQB3616 or any adjuvant in the capsule Patients who took part in other trials within 4 weeks; Patients with concomitant diseases which could seriously endanger themselves or those who won't complete the study according to investigators;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TQB3616<br>TQB3616 administerde days 28 of a 28-day schedule,doses ranging from 20m to 120mg once daily | Drug: TQB3616<br>* TQB3616 administerde days 28 of a 28-day schedule,doses ranging from 20m，40mg，60mg，80mg，100mg，120mg once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLT | Dose-Limiting Toxicities | Baseline up to 28 days | 
| MTD | Maximum Tolerated Dose | Baseline up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum Observed Plasma Concentration | Hour 0(pre-dose),1,2,4,6,8,12,24,36,48,72,120,168hours post-dose on single dose ; Hour 0(pre-dose) of day1,day7,day14,day21,day28 on multiple dose and Hour 0(pre-dose),1,2,4,6,8,12,24hours post-dose on multiple dose of day28 | 
| Tmax | Maximum Observed Plasma Concentration | Hour 0(pre-dose),1,2,4,6,8,12,24,36,48,72,120,168hours post-dose on single dose ; Hour 0(pre-dose) of day1,day7,day14,day21,day28 on multiple dose and Hour 0(pre-dose),1,2,4,6,8,12,24hours post-dose on multiple dose of day28 | 
| t1/2 | Terminal Half-life | Hour 0(pre-dose),1,2,4,6,8,12,24,36,48,72,120,168hours post-dose on single dose ; Hour 0(pre-dose) of day1,day7,day14,day21,day28 on multiple dose and Hour 0(pre-dose),1,2,4,6,8,12,24hours post-dose on multiple dose of day28 | 
| AUC | Area Under the Curve | Hour 0(pre-dose),1,2,4,6,8,12,24,36,48,72,120,168hours post-dose on single dose ; Hour 0(pre-dose) of day1,day7,day14,day21,day28 on multiple dose and Hour 0(pre-dose),1,2,4,6,8,12,24hours post-dose on multiple dose of day28 |