Clinical trial NCT02649361 (phase 2, status: completed)
Conditions: esophageal squamous cell carcinoma
ICD codes: C22.0, C4A.9, C7B.1, C4A.0, C4A.31, C4A.51, C4A.8
Drugs: anlotinib, placebo
SMILES: [H][C@]12COC(=O)[C@]1([H])[C@H](C1=CC(OC)=C(O)C(OC)=C1)C1=CC3=C(OCO3)C=C1[C@H]2O[C@@H]1O[C@]2([H])CO[C@@H](C)O[C@@]2([H])[C@H](O)[C@H]1O, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
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