A Phase I Study of Anlotinib on Tolerance and Pharmacokinetics

Study Overview
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Brief Summary
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Anlotibib (ALTN) is a kind of innovative medicines approved by State Food and Drug Administration（SFDA） which was researched by Jiangsu Chia-tai Tianqing Pharmaceutical Co., Ltd. ALTN is a kinase inhibitor of receptor tyrosine with multi-targets, especially for VEGFR2 and VEGFR3. It has the obvious resistance to new angiogenesis.

Detailed Description
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The primary objective of this trial is to explore the maximum tolerated dose(MTD), dose-limiting toxicity(DLT) of ALTN and rational dosage regimen for phase II study, to investigate the pharmacokinetics with single and multiple doses of ALTN from 5mg/d,10mg/d,16mg/d,12mg.

Official Title
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A Phase I Study of Anlotinib on Tolerance and Pharmacokinetics

Conditions
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Advanced Cancer

Intervention / Treatment
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* Drug: anlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: late malignant tumor patients diagnosed with the pathological and/or cytological; lack of the standard treatment or treatment failure; 18-65years, ECOG:0-1,Expected survival period >3 months; stop medicine > 30 days if any other chemotherapy drugs be used. HB≥90g/L,ANC(Absolute Neutrophil Count) ≥1.5×109/L；PLT ≥100×109/L ,BIL/ALT/AST(aspartate aminotransferase )/Cr in normal range,or CCR≥60ml/min,TG≤ 3.0mmol/L，cholesterol≤7.75mmol/L; LVEF≥LLN. Female should be agreed to use contraceptive during the study and after 6 months (such as intrauterine device(IUD), the pill or a condom); The serum or urine pregnancy test negative before take ALTN, and is out of non-lactation period. Male should be agreed to use contraceptive during the study and after the period of 6 months. Volunteer, informed consent form (ICF) signed, compliance. Exclusion Criteria: Subject was diagnosed with other malignant tumors previously or meanwhile; Participated in other clinical trials in four weeks; Has influence of oral drugs(such as unable to swallow, gastrointestinal tract after resection); Already diagnosed with brain metastases, spinal cord compression, cancerous meningitis, or screening CT or MRI findings of the brain or soft meningeal disease patient; Hypertension Urine protein: ++, and urinary in 24 hours > 1.0g; Coagulant function abnormality: subject with bleeding tendency (such as active peptic ulcer) or are receiving thrombolysis or anticoagulant therapy; Subject with psychiatric drugs abuse history and can't get rid of, or mental disorder; With artery/venous thrombotic before oral ALTN; With history of anticoagulant, vitamin K antagonists(such as warfarin or heparin) or other analogues treatment; With Abnormal thyroid function; With history of psychiatric drugs abuse or a mental disorder; Viral hepatitis B or hepatitis c patients (including hepatitis b, hepatitis c virus carriers); Have immunodeficiency history; According to the researcher's judgment,there are concomitant diseases which will seriously endanger the patients or obstruct the patients to complete the clinical trial.

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>dosage form:capsule dosage:5mg,10mg,16mg,12mg frequency:once one day duration:Continuous two weeks then stop a week | Drug: anlotinib<br>* oral medicine.<br>* Other names: ALTN;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax Cmax t1/2 AUC | To collect point with single drug:H0/H0.5/H1/H2/H4/H8/H12/H24/H48/H72/H96/H120/H144/H/H168/H192/H216/H240 To collect point with multiple drug:d1/d2/d4/d7/d10/d14/d15/d21/d22/d28/d35/d42 | Up to 52 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | blood examination, urine examination, stool examination, blood biochemical (ALT, AST, TB(total bilirubin), DB, BUN, Cr, blood electrolyte), electrocardiogram (ecg), thyroid function, the function of blood coagulation, etc | Up to 21 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced cancer