Study of Anlotinib in Patients With Esophageal Squamous Cell Carcinoma (ALTER1102)

Inclusion Criteria:

• Histological documentation of esophageal squamous cell carcinoma；

• Advanced esophageal squamous cell carcinoma with distant metastasis(Stage IV),at leastone measurable lesion (by RECIST1.1)

• Patients who at least have failed to a platinum-based chemotherapy treatment orchemotherapy containing paclitaxel. Note: (1) Each line treatment refers to treatment duration at least one cycle usingmonotherapy or drug combination; (2)Adjuvant chemotherapy or neoadjuvant chemoradiation ispermitted before the study (if disease recurred during adjuvant chemotherapy/neoadjuvantchemoradiation or recurred within 6 months after stopping treatment, adjuvantchemotherapy/neoadjuvant chemoradiation can be considered as first line systemicchemotherapy;

• 18-75 years,ECOG PS:0-2,Life expectancy of more than 3 months

• 4 weeks or more from the last cytotoxic therapy, radiation therapy or surgery

• Main organs function is normal

• Women of childbearing potential should agree to use and utilize an adequate method ofcontraception (such as intrauterine device，contraceptive and condom) throughouttreatment and for at least 6 months after study is stopped；the result of serum orurine pregnancy test should be negative within 7 days prior to study enrollment，andthe patients required to be non-lactating；Man participants should agree to use andutilize an adequate method of contraception throughout treatment and for at least 6months after study is stopped

• Patients should participate in the study voluntarily and sign informed consent

Exclusion Criteria:

• Patients whose primary lesion with active bleeding within 2 months

• Primary lesion not resected and has not shrinked after radiation therapy

• Patients who have been failure with anti-tumor angiogenesis drug treatment

• Patients with factors that could affect oral medication (such as dysphagia，chronicdiarrhea, intestinal obstruction etc.)

• Brain metastases patients with symptoms or symptoms controlled < 3 months

• Patients with any severe and/or unable to control diseases，including：

1. Blood pressure unable to be controlled ideally(systolic pressure≥150mmHg，diastolic pressure≥100 mmHg);

2. Patients with Grade 1 or higher myocardial ischemia, myocardial infarction ormalignant arrhythmias(including QT≥480ms) and patients with Grade 1 or highercongestive heart failure (NYHA Classification);

3. Patients with active or unable to control serious infections;

4. Patients with cirrhosis, decompensated liver disease, or active hepatitis;

5. Patients with poorly controlled diabetes (fasting blood glucose(FBG)＞10mmol/L)

6. Urine protein ≥ ++，and 24-hour urinary protein excretion＞1.0 g confirmed

• Patients with non-healing wounds or fractures

• Patients with any CTC AE Grade 1 or higher bleeding events occurred in the lungs orany CTC AE Grade 2 or higher bleeding events occurred within 4 weeks prior toassignment;Patients with any physical signs of bleeding diathesis or receivingthrombolysis and anticoagulation

• Patients with arterial or venous thromboembolic events occurred within 6 months, suchas cerebrovascular accident (including transient ischemic attack), deep veinthrombosis and pulmonary embolism

• Patients with drug abuse history and unable to get rid of or Patients with mentaldisorders

• Imaging showed tumors have involved important blood vessels or by investigatorsdetermine likely during the follow-up study and cause fatal hemorrhage

• Patients participated in other anticancer drug clinical trials within 4 weeks

• History of immunodeficiency

• Patients with concomitant diseases which could seriously endanger their own safety orcould affect completion of the study according to investigators' judgment