Phase I Study of Chiauranib in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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The purpose of this dose-escalation study is to assess the safety and tolerability of treatment with Chiauranib administered orally over a range of doses in patients with advanced solid tumors.

Detailed Description
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The purpose of this study is to assess the tolerability and safety include adverse events, vital signs, laboratory tests ,etc., of a range of doses of Chiauranib in solid tumor patients, and to determine the dose limit toxicity and the maximum tolerable dose.

Official Title
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Phase I Safety and Pharmacokinetics Study of Chiauranib in Patients With Advanced Solid Tumors

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: Chiauranib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological or cytological confirmation of advanced solid tumor, including non-small cell lung cancer, colorectal cancer, ovarian cancer, renal cell carcinoma, gastrointestinal stromal tumor, gastric cancer, et al; Patients with advanced solid tumors refractory to standard therapy or for which no standard therapy exists; Body mass index (BMI) is between 18 and 28; Age: 18 65 years; Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1; Laboratory criteria are as follows: Complete blood count: hemoglobin (Hb) ≥100g/L (no blood transfusion within 14 days); absolute neutrophil count (ANC) ≥1.5×109/L ; platelets >=100×109/L Biochemistry test: serum creatinine <=1.5×upper limit of normal (ULN); total bilirubin≦1.5×ULN; alanine aminotransferase / aspartate aminotransferase≦1.5×ULN; fasting triglyceride (TG) <= 3.0 mmol/L; total cholesterol <= 7.75 mmol/L Coagulation test: International Normalized Ratio (INR) < 1.5 Women of child-bearing potential should be non-lactating patients, and must agree to use effective contraceptive methods prior to study entry, during study participation, and up to 6 months following completion of therapy. A serum or urine pregnancy test within 7 days before enrollment must be negative; Men must agree to use effective contraceptive methods during study participation and up to 6 months following completion of therapy; Willingness to sign a written informed consent document Exclusion Criteria: Life expectation < 3 months; Subjects received anti-cancer therapy (including chemotherapy, radiotherapy, targeted therapy and endocrine therapy, et al) within 4 weeks prior to study entry; Subjects received nitrosoureas or mitomycin chemotherapy within 6 weeks prior to study entry; Have uncontrolled or significant cardiovascular disease, including: Myocardial infarction (< the last 12 months) Uncontrolled angina (< the last 6 months) Congestive heart failure (< the last 6 months), or Left Ventricular Ejection Fraction (LVEF) < 50% prior to study entry History of any significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or TdP) History of significant QT interval prolongation, or Corrected QT Interval (QTc) > 450 ms prior to study entry History of cerebrovascular accident Symptomatic coronary heart disease requiring treatment with agents Uncontrolled hypertension (> 140/90 mmHg) by single agent; Have active bleeding , current thrombotic disease, or patients with bleeding potential receiving anticoagulation therapy; History of deep vein thrombosis or pulmonary embolism; Have unsolved toxicities (> grade 1) from prior anti-cancer therapy; Have clinical significant gastrointestinal abnormality, e.g., unable to swallow, chronic diarrhea, ileus, that would impair the ingestion,transportation or absorption of oral agents, or patients undergone gastrectomy; Have symptomatic brain metastasis; History of organ transplantation; Proteinuria positive; Congenital or acquired immunodeficiency, active infections; Any mental or cognitive disorder, that would impair the ability to understand the informed consent document or the operation and compliance of study; Any other condition which is inappropriate for the study in the opinion of the investigators.

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: Chiauranib<br>Patients take a single dose of Chiauranib capsules for the pharmacokinetic study,then off for 5 days before the first cycle begins. In the subsequent treatment cycles, Chiauranib capsules are given orally once daily, 28 days as a cycle. | Drug: Chiauranib<br>* Take orally<br>* Other names: CS2164;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| dose-limiting toxicity (DLT) |  | day 1-28 | 
| Number of Adverse Events |  | An expected average of 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pharmacokinetic profile of Chiauranib |  | On day 1,8,15,22,25,26,27,28 | 
| Evidence of benefit | clinical benefit rate (complete response (CR),partial response (PR),stable disease (SD) > 8 weeks),duration of response (DOR),time to progression (TTP), or tumor marker improvement, if appropriate | An expected average of 8 months | 
| Pharmacodynamic profile of Chiauranib | Plasma biomarkers: soluble vascular endothelial growth factor receptors (sVEGFR2), vascular endothelial growth factor (VEGF) Tumor tissue biomarkers: Aurora B, phospho-histone H3 | On day 15,28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chiauranib, advanced solid tumors, phase 1 study