Tolerance and Pharmacokinetics of TQ-B3233

Study Overview
=================
Brief Summary
-----------------
Study of Tolerance and Pharmacokinetics of TQ-B3233 Capsule, phase I,single arm.

Detailed Description
-----------------
The maximum tolerated dose (MTD) of TQ-B3233 [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]The highest dose at which no more than 33% of the subjects experience a dose-limiting toxicity (DLT) during treatment. Pharmacokinetics of TQ-B3233 (in whole blood):In the study of single-dose, full PK profiles will be obtained at H0/H0.5/H1/H2/H3/H5/H8/H10/H12/H24/H48/H72（H means Hour）.In the study of multiple-dose,full PK profiles will be obtained at D0/D1/D2/D8/D15/D22/D28（D means Day）.

Official Title
-----------------
To Study the Pharmacokinetic Characteristics of TQ-B233 in the Human Body, Recommend a Reasonable Regimen for Subsequent Research

Conditions
-----------------
Tumor

Intervention / Treatment
-----------------
* Drug: TQ-B3233


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients definitely diagnosed by pathology and/or cytology as BRAF mutation advanced malignant melanoma. 18-70 years old, ECOG PS:0-1,Life expectancy of more than 3 months; Patients treated with chemotherapy agents or surgery before being enrolled into the study need waiting for 4 weeks, 6 weeks will be needed if agents were nitrocarbamide and mitomycin C; Main organs function is normal; Women of childbearing potential should agree to use and utilize an adequate method of contraception (such as intrauterine device，contraceptive and condom) throughout treatment and for at least 6 months after study is stopped；the result of serum or urine pregnancy test should be negative within 7 days prior to study enrollment，and the patients required to be non-lactating；Man participants should agree to use and utilize an adequate method of contraception throughout treatment and for at least 6 months after study is stopped; Patients should be voluntary and sign the informed consent before taking part in the study; Exclusion Criteria: Patients with Malignant tumors within 5 years, except for non-melanoma skin cancer and in situ cancer; Patients who had previously received specific BRAF inhibitors; A variety of factors that affect oral medication (such as inability to swallow, gastrointestinal resection, chronic diarrhea, intestinal obstruction, etc.) Patients who participated in other anticancer drug clinical trials within 4 weeks ; Blood pressure unable to be controlled ideally by one drug(systolic pressure≥150 mmHg，diastolic pressure≥90 mmHg); Patients with Grade 1 or higher myocardial ischemia, myocardial infarction or malignant arrhythmias or cardiac insufficiency (including QTc≥480ms) and patients with Grade 3 or higher congestive heart failure (NYHA Classification); Patients with non-healing wounds or fractures; 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; Patients with drug abuse history or unable to get rid of drugs or Patients with mental disorders; Coagulation function abnormality: haemorrhagic tendencies (e.g. active digestive tract ulcer), or are receiving thrombolytic or anticoagulant therapy; Patients with immunodeficiency, including HIV positive or other acquired, congenital immunodeficiency disease, or organ transplant history; Patients with thyroid dysfunction; Patients with concomitant diseases which could seriously endanger themselves or those who won't complete the study according to investigators; Parents with hepatitis b surface antigen positive or HCV;

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TQ-B3233 capsule<br>QD or BID; patients are given the doses according to the protocal, and a cycle is 28 days. | Drug: TQ-B3233<br>* QD or BID in different stage of this research<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum tolerated dose(MTD) |  | 28 Days | 
| dose-limiting toxicity(DLT) |  | 28 Days | 
| Peak Plasma Concentration(Cmax) |  | up to 28 Days | 
| Peak time(Tmax) |  | up to 28 Days | 
| Half life(t1/2) |  | up to 28 Days | 
| Area under the plasma concentration versus time curve (AUC) |  | up to 28 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) |  | up to 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
TQ-B3233, tumor, toleration, pharmacokinetics