A Phase I Study of TQB3616 on Tolerance and Pharmacokinetics

Phase 1

• Conditions: Advanced Breast Cancer
• Interventions: Drug: TQB3616

• Registration Number: NCT03850873
• Lead Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2019-02
• Study First Submitted: 2019-02-20
• Study First Submitted QC: 2019-02-20
• Last Update Submitted: 2019-02-20
• Study First Posted: 2019-02-22
• Last Update Posted: 2019-02-22
• Study Start: 2019-03-01
• Primary Completion: 2020-09-30
• Study Completion: 2021-09-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 30

Inclusion Criteria

1. ≥18 years old
2. Patients definitely diagnosed by pathology and/or cytology as advanced breast cancer with ER+、Her2-,who failed with standard endocrine therapy.
3. ECOG PS:0-1,Survival is expected to be greater than 3 months
4. 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

1. Patients with malignant tumors, except for Cured cutaneous basal cell carcinoma and cervical carcinoma in situ
2. Prior treatment with chemotherapy with cytotoxic drugs within 4 weeks, mitomycin C or nirtosocarbamide within 8 weeks
3. Prior treatment with any anti-cancer therapy including hormone therapy radioimmunotherapy, molecular targeted therapy, immunotherapy or other biological therapy with 2 weeks
4. Patients treated with other CDK4/6 inhibitors;
5. 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;
6. Previous history of stem cell or bowe marrow transplant;
7. A variety of factors that affect oral medication (such as inability to swallow, gastrointestinal resection, intestinal obstruction, etc.)
8. Patients with non-healing wounds or fractures, except for bone metastatics with pathologic frature
9. 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)
10. Patients who need to take CYP3A4 inhibitors or inducers from the screening period;
11. Patients with drug abuse history or unable to get rid of drugs or Patients with mental disorders
12. Patients with the urine protein≥2+, total ammount of 24 hours urinary protein determination>1.0 grams;
13. Patients with hyperactive/venous thrombosis events within 6 months,such as cerebrovascular accidents (including temporary ischemic attack), deep venous thrombosis and pulmonary embolism
14. Patients with active hepatitis b or c infection
15. Patients with immunodeficiency, including HIV positive or other acquired, congenital immunodeficiency disease, or organ transplant history;
16. Patients allergic to TQB3616 or any adjuvant in the capsule
17. Patients who took part in other trials within 4 weeks;
18. Patients with concomitant diseases which could seriously endanger themselves or those who won't complete the study according to investigators;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TQB3616	TQB3616	TQB3616 administerde days 28 of a 28-day schedule,doses ranging from 20m to 120mg once daily

Primary Outcome Measures

Name	Time	Method
DLT	Baseline up to 28 days	Dose-Limiting Toxicities
MTD	Baseline up to 28 days	Maximum Tolerated Dose

Secondary Outcome Measures

Name	Time	Method
Cmax	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	Maximum Observed Plasma Concentration
Tmax	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	Maximum Observed Plasma Concentration
t1/2	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	Terminal Half-life
AUC	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	Area Under the Curve