Phase I Study of Chiauranib in Patients With Advanced Solid Tumors

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.

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.