A Phase I Additional Study of Anlotinib on Tolerance and Pharmacokinetics

Study Overview
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Brief Summary
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A Phase I Additional Study of Anlotinib on Tolerance and Pharmacokinetics.To further study the pharmacokinetic characteristics of Anlotinib in the human body, recommend a reasonable regimen for subsequent research.

Official Title
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Phase I Additional Study of Tolerance and Pharmacokinetics of Anlotinib in Patients With Advanced Solid Tumors

Conditions
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Cancer

Intervention / Treatment
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* Drug: Anlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological documentation of Advanced solid tumors except the digestive tract tumors,at least one measurable lesion (by RECIST1.1) Lack of the standard treatment or treatment failure 18-65 years,ECOG PS:0-1,Life expectancy of more than 3 months 30 Days or more from the last cytotoxic therapy 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 participate in the study voluntarily and sign informed consent Exclusion Criteria: Patients who are used by anlotinib Patients with factors that could affect oral medication (such as dysphagia，chronic diarrhea, intestinal obstruction etc.) Brain metastases patients with symptoms or symptoms controlled < 3 months Patients with any severe and/or unable to control diseases，including： Blood pressure unable to be controlled ideally(systolic pressure≥150 mmHg，diastolic pressure≥100 mmHg); Patients with Grade 1 or higher myocardial ischemia, myocardial infarction or malignant arrhythmias(including QT≥480ms) and patients with Grade 1 or higher congestive heart failure (NYHA Classification); Patients with active or unable to control serious infections; Patients with cirrhosis, decompensated liver disease, or active hepatitis; Patients with poorly controlled diabetes (fasting blood glucose(FBG)>10mmol/L) Urine protein ≥ ++，and 24-hour urinary protein excretion>1.0 g confirmed Patients with non-healing wounds or fractures Patients with any CTC AE Grade 1 or higher bleeding events occurred in the lungs or any CTC AE Grade 2 or higher bleeding events occurred within 4 weeks prior to assignment;Patients with any physical signs of bleeding diathesis or receiving thrombolysis and anticoagulation Patients with drug abuse history and unable to get rid of or Patients with mental disorders Patients participated in other anticancer drug clinical trials within 4 weeks History of immunodeficiency Patients with concomitant diseases which could seriously endanger their own safety or could affect completion of the study according to investigators' judgment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

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: Anlotinib<br> | Drug: Anlotinib<br>* Anlotinib QD po. and it should be continued until disease progression or intolerable toxicity or patients withdrawal of consent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of Anlotinib (in whole blood):Peak Plasma Concentration(Cmax) | Peak Plasma Concentration(Cmax),Cmax in ng/mL.In the study of single-dose, full PK profiles will be obtained at H0/H1/H2/H4/H8/H11/H24/H48/H72/H120/H168/H240（H means Hour）.In the study of multiple-dose,full PK profiles will be obtained at D1/D4/D7/D10/D14/D18/Before the next cycle（D means Day）. | up to 18 Days (endpoint when the two consecutive time points of blood drug concentration <150 DPM/mL) | 
| Pharmacokinetics of Anlotinib (in whole blood):Peak time（Tmax） | Peak time（Tmax）,Tmax in h.In the study of single-dose, full PK profiles will be obtained at H0/H1/H2/H4/H8/H11/H24/H48/H72/H120/H168/H240(H means hour).In the study of multiple-dose,full PK profiles will be obtained at D1/D4/D7/D10/D14/D18/Before the next cycle(D means Day). | up to 18 Days (endpoint when the two consecutive time points of blood drug concentration <150 DPM/mL) | 
| Pharmacokinetics of Anlotinib (in whole blood):Half life（t1/2） | Half life（t1/2）,t1/2 in h.In the study of single-dose, full PK profiles will be obtained at H0/H1/H2/H4/H8/H11/H24/H48/H72/H120/H168/H240(H mans Hour).In the study of multiple-dose,full PK profiles will be obtained at D1/D4/D7/D10/D14/D18/Before the next cycle(D means Day). | up to 18 Days (endpoint when the two consecutive time points of blood drug concentration <150 DPM/mL) | 
| Pharmacokinetics of Anlotinib (in whole blood):Area under the plasma concentration versus time curve (AUC) | Area under the plasma concentration versus time curve (AUC), AUC in ng.h/mL.In the study of single-dose, full PK profiles will be obtained at H0/H1/H2/H4/H8/H11/H24/H48/H72/H120/H168/H240(H means Hour).In the study of multiple-dose,full PK profiles will be obtained at D1/D4/D7/D10/D14/D18/Before the next cycle(D means Day). | up to 18 Days (endpoint when the two consecutive time points of blood drug concentration <150 DPM/mL) | 
| Pharmacokinetics of Anlotinib (in whole blood):Clearance（CL） | Clearance（CL）,CL in L/h.In the study of single-dose, full PK profiles will be obtained at H0/H1/H2/H4/H8/H11/H24/H48/H72/H120/H168/H240(H means Hour).In the study of multiple-dose,full PK profiles will be obtained at D1/D4/D7/D10/D14/D18/Before the next cycle(D means Day). | up to 18 Days (endpoint when the two consecutive time points of blood drug concentration <150 DPM/mL) | 
| Cumulative excretion of Anlotinib (in urine) |  | up to 10 Days(endpoint when the two consecutive time points of cumulative excretion <1%) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) |  | each 42 days up to intolerance the toxicity or PD(Disease progression) (up to 24 months) |