A Study of Apatinib Plus Radiotherapy and S-1 for Treatment of Refractory or Metastatic Esophageal Squamous Cell Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of patients who receive apatinib plus radiotherapy and S-1 for treatment of refractory or metastatic esophageal squamous cell carcinoma.

Official Title
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A Prospective Study of Apatinib Plus Radiotherapy and S-1 for Treatment of Refractory or Metastatic Esophageal Squamous Cell Carcinoma

Conditions
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Refractory or Metastatic Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Combination Product: apatinib S-1 radiotherapy
* Combination Product: S-1 radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Age:18 to 70 years old (man or female); 2. Imageology diagnosed with refractory or metastatic esophageal squamous cell carcinoma(pathologically diagnosed with supraclavicular lymph node metastasis and anastomotic recurrence ); 3. The distant metastatic is oligotransfera, with radiotherapy indication; 4. Patients with measurable lesions(measuring≥10mm on spiral CT scan, satisfying the criteria in RECIST1.1); 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; 6. Major organ function has to meet the following certeria: For results of blood routine test (without blood transfusion within 14 days) HB≥100g/L; ANC≥3.0×109/L; PLT≥100×109/L; For results of blood biochemical test： TBIL<1.5×ULN； ALT and AST<2.5×ULN, but< 5×ULN if the transferanse elevation is due to liver metastases； Serum creatinine ≤1ULN , calculated creatinine clearance>50 ml/min(per the Cockcroft-Gault formula); 7. Life expectancy greater than or equal to 3 months; 8. Women of childbearing age must have contraceptive measures or have test pregnancy (serum or urine) enroll the study before 7 days, and the results must be negative, and take the methods of contraception during the test and the last to have drugs after 8 weeks. Men must be contraception or has sterilization surgery during the test and the last to have drugs after 8 weeks; 9. Coagulation function is normal, without active hemorrhage and thrombosis: INR<1.5×ULN APTT<1.5×ULN PT<1.5ULN 10. Participants were willing to join in this study, and written informed consent; 11. Participants were good adherence, cooperate with the follow-up. Exclusion Criteria: 1. Allergic to apatinib; 2. Have high blood pressure and antihypertensive drug treatment can not control (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg), with classⅡand above coronary heart disease and arrhythmia (including QTc lengthened men > 450 ms, women > 470 ms) and cardiac insufficiency; 3. A variety of factors influencing oral drugs (such as unable to swallow, nausea, vomiting, chronic diarrhea and intestinal obstruction, etc.); 4. Patients with tendency of gastrointestinal bleeding, including the following; Active ulcerative lesions, and defecate occult blood (+ +); Has melena and hematemesis in three months; For defecate occult blood (+) or(+/-) ,must be received gastroscopy, the physicians consider there are potential bleeding risk with ulcers, hemorrhagic diseases; 5. Coagulant function abnormality (INR > 1.5 ULN, APTT > 1.5 ULN), with bleeding tendency; 6. Patients with thrombosis or anticoagulant drug therapy; 7. Patients with symptoms of central nervous system metastasis; Patients with other malignant tumors within 5 years (except for the treated skin basal cell carcinoma and cervical carcinoma in situ); 8. history of psychiatric drugs abuse and can't quit or patients with mental disorders; 9. Less than 4 weeks from the last clinical trial; 10. Have received prior treatment with anti- VEGF/VEGFR; 11. Researchers considered there are serious harm to patient safety or affect the patients who have completed the study; 12. Pregnant or lactating women; 13. The researchers think inappropriate.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: apatinib and S-1 radiotherapy<br>apatinib 500mg qd po S-1 40-60mg/time bid po d1-14 q3w radiotherapy 50-60Gy/25-30times until disease progression or intolerable toxicity or patients withdrawal of consent | Combination Product: apatinib S-1 radiotherapy<br>* apatinib 500mg qd po S-1 40-60mg/time bid po d1-14 q3w radiotherapy 50-60Gy/25-30times until disease progression or intolerable toxicity or patients withdrawal of consent<br>|
| Active Comparator: S-1 radiotherapy<br>S-1 40-60mg/time bid po d1-14 q3w radiotherapy 50-60Gy/25-30times until disease progression or intolerable toxicity or patients withdrawal of consent | Combination Product: S-1 radiotherapy<br>* S-1 40-60mg/time bid po d1-14 q3w radiotherapy 50-60Gy/25-30times until disease progression or intolerable toxicity or patients withdrawal of consent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | Baseline to measured date of progression or death from any cause | evaluated in 24 months since the treatment began | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Baseline to measured date of death from any cause | the first day of treatment to death or last survival confirm date，up to 24 months | 
| Disease control rate | Baseline to measured progressive disease | tumor assessment every 6 weeks ，up to 24 month | 
| Objective response rate | Baseline to measured stable disease | tumor assessment every 6 weeks，up to 24 months | 
| Side effects | throughout study | evaluated in the 24th month since the treatment began according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 |