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

To compare the effects and safety of Anlotinib with placebo in patients with esophageal squamous cell carcinoma(ESCC).


Eligibility Criteria:
Inclusion Criteria:

* Histological documentation of esophageal squamous cell carcinoma；
* Advanced esophageal squamous cell carcinoma with distant metastasis(Stage IV),at least one measurable lesion (by RECIST1.1)
* Patients who at least have failed to a platinum-based chemotherapy treatment or chemotherapy containing paclitaxel.

Note: (1) Each line treatment refers to treatment duration at least one cycle using monotherapy or drug combination; (2)Adjuvant chemotherapy or neoadjuvant chemoradiation is permitted before the study (if disease recurred during adjuvant chemotherapy/neoadjuvant chemoradiation or recurred within 6 months after stopping treatment, adjuvant chemotherapy/neoadjuvant chemoradiation can be considered as first line systemic chemotherapy;

* 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 of contraception (such as intrauterine device，contraceptive and condom) throughout treatment and for at least 6 months after study is stopped；the result of serum or urine pregnancy test should be negative within 7 days prior to study enrollment，and the patients required to be non-lactating；Man participants should agree to use and utilize an adequate method of contraception throughout treatment and for at least 6 months 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，chronic diarrhea, 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≥150 mmHg，diastolic pressure≥100 mmHg);
  2. Patients with Grade 1 or higher myocardial ischemia, myocardial infarction or malignant arrhythmias(including QT≥480ms) and patients with Grade 1 or higher congestive 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 or any CTC AE Grade 2 or higher bleeding events occurred within 4 weeks prior to assignment;Patients with any physical signs of bleeding diathesis or receiving thrombolysis and anticoagulation
* Patients with arterial or venous thromboembolic events occurred within 6 months, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis and pulmonary embolism
* Patients with drug abuse history and unable to get rid of or Patients with mental disorders
* Imaging showed tumors have involved important blood vessels or by investigators determine 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 or could affect completion of the study according to investigators' judgment