Phase I Study of Chiauranib in Patients With Advanced Solid Tumors

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

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.

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:

1. 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;

2. Patients with advanced solid tumors refractory to standard therapy or for which no standard therapy exists;

3. Body mass index (BMI) is between 18 and 28;

4. Age: 18~65 years;

5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;

6. Laboratory criteria are as follows:

   1. 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
   2. 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
   3. Coagulation test: International Normalized Ratio (INR) < 1.5

7. 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;

8. Willingness to sign a written informed consent document

Exclusion Criteria:

1. Life expectation < 3 months;

2. 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;

3. Have uncontrolled or significant cardiovascular disease, including:

   1. Myocardial infarction (< the last 12 months)
   2. Uncontrolled angina (< the last 6 months)
   3. Congestive heart failure (< the last 6 months), or Left Ventricular Ejection Fraction (LVEF) < 50% prior to study entry
   4. History of any significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or TdP)
   5. History of significant QT interval prolongation, or Corrected QT Interval (QTc) > 450 ms prior to study entry
   6. History of cerebrovascular accident
   7. Symptomatic coronary heart disease requiring treatment with agents
   8. Uncontrolled hypertension (> 140/90 mmHg) by single agent;

4. Have active bleeding , current thrombotic disease, or patients with bleeding potential receiving anticoagulation therapy;

5. History of deep vein thrombosis or pulmonary embolism;

6. Have unsolved toxicities (> grade 1) from prior anti-cancer therapy;

7. 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;

8. Have symptomatic brain metastasis;

9. History of organ transplantation;

10. Proteinuria positive;

11. Congenital or acquired immunodeficiency, active infections;

12. Any mental or cognitive disorder, that would impair the ability to understand the informed consent document or the operation and compliance of study;

13. Any other condition which is inappropriate for the study in the opinion of the investigators.