Phase 3 Clinical Study of Chiauranib Capsule in Patients With Small-cell Lung Cancer

Prior treatment

• Patients with second primary cancer, except: adequately treated basal cell or squamous cell skin cancer, curatively treated in-situ cancer of the cervix, unless received curative treatment and with documented evidence of no recurrence during the past five years
• Patients who have been used aurora kinase inhibitors, or VEGF/VEGFR inhibitors
• Patients have used any anti-cancer therapy, including adiotherapy, chemotherapy, immunotherapy, target therapy, and other anti-tumor treatments within 28 days before the first dose
• Patients have used experimental drugs or devices within 28 days before the first dose
• Patients received major surgical operations within 28 days before the first dose, or patients with serious non-healing wounds, ulcer or fracture at the time of screening
• Obstructive atelectasis that requires chest radiotherapy or surgery during the screening period or CT or MRI of the chest during the screening period shows interstitial lung disease or pulmonary fibrosis or lung inflammation that requires treatment, or within 6 months before the first dose history of pneumonia requiring oral or intravenous steroid treatment
• Active bleeding within 2 months before the first dose, or anticoagulant drugs are being taken during the screening period, or the investigator judges that there is a high risk of bleeding during the screening period
• History of deep vein thrombosis or pulmonary embolism within 6 months before the first dose
• Candidates with drug and alcohol abuse

Other illness

• Screening period imaging shows that the tumor has invaded the periphery of important blood vessels or the investigator judges that the tumor is likely to invade important blood vessels and cause hemorrhage during the trial
• With the exception of alopecia, any ongoing toxicities (\>CTCAE grade 1) caused by previous cancer therapy
• Patients with factors that could affect oral medication (such as dysphagia，chronic diarrhea, intestinal obstruction, After small bowel resection,etc), or undergone gastrectomy, or history of gastrointestinal perforation
• Active infections that require systemic treatment (oral, intravenous infusion) during the screening period
• Screening for HIV antibody positive
• Screening test for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive with virus replication, hepatitis C antibody (HCV-Ab) positive with virus replication
• Any mental or cognitive disorder, that would impair the ability to understand the informed consent document, or the compliance of study
• Any other condition which is inappropriate for the study according to investigators' judgment.

Lab values

• Patients with uncontrolled or significant cardiovascular disease, including:
  • Grade II or higher Congestive heart failure, unstable angina pectoris, myocardial infarction (NYHA Classification) within 6 months prior to study entry; or arrhythmia requiring treatment, or Left Ventricular Ejection Fraction (LVEF) \< 50% during screening stage.
  • Primary cardiomyopathy (dilated cardiomyopathy, hypertrophic cardiomyocyte, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, et,al).
  • History of significant QT interval prolongation, or Corrected QT Interval QTc≥450ms(male),QTc≥470ms（female）at screening.
  • patient's treatment record of using at least 2 antihypertensive drugs at the same Within 14 days before the first dose, or uncontrolled hypertension (\> 140/90 mmHg) during the screening period.

Other

• Patients who known to brain metastases with neurological symptoms;
• Pleural fluid, ascites, pericardial effusion with clinical symptoms or need to be drained during the screening period
• Proteinuria positive(≥1g/24h)
• Women of childbearing potential not willing to use and utilize an adequate method of contraception (such as intrauterine device, contraceptive and condom) throughout treatment and for at least 12 weeks after the last dose; pregnant or breastfeeding women; the result of urine pregnancy test was positive at screening; Man participants not willing to use and utilize an adequate method of contraception throughout treatment.

• Male or female, age ≥ 18 years and ≤75 years;
• Cytologically or histologically confirmed small cell lung cancer;
• Patients have received at least 2 different systemic chemotherapy regimens (contained platinum based regimen) , and progressed or relapsed
• At least one measurable lesion that can be accurately assessed ( RECIST1.1 criteria). If the only site of measurable disease is in a previously irradiated area, the patient must have documented progression of disease in this area.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Laboratory criteria are as follows:
  • Complete blood count: absolute neutrophil count (ANC) ≥1.5×10\^9/L ; platelets ≥75×10\^9/L; hemoglobin (Hb) ≥80g/L ;
  • Biochemistry test: total bilirubin≤1.5×ULN; alanine aminotransferase (ALT) , aspartate aminotransferase(AST)≤2.5×ULN(ALT,AST≦5×ULN if liver involved); serum creatinine(cr)≤1.5×ULN;
  • Coagulation test: International Normalized Ratio (INR) \< 1.5.
• Life expectancy of at least 3 months.
• All patients must have given signed, informed consent prior to registration on study.