A Prospective Study of Apatinib Plus Concurrent Neoadjuvant Chemoradiotherapy for Siewert II ，III of Locally Advanced HER-2 Negative Adenocarcinoma at Gastroesophageal Junction

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 concurrent neoadjuvant chemoradiotherapy for Siewert II ，III of locally advanced HER-2 negative adenocarcinoma at gastroesophageal junction.

Official Title
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A Prospective Study of Apatinib Plus Concurrent Neoadjuvant Chemoradiotherapy for Siewert II ，III of Locally Advanced HER-2 Negative Adenocarcinoma at Gastroesophageal Junction

Conditions
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Gastroesophageal Junction Adenocarcinoma

Intervention / Treatment
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* Drug: apatinib
* Drug: Capecitabine
* Drug: Oxaliplatin
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age:18 to 70 years old (man or female); Conﬁrmed to Siewert II , III of locally advanced adenocarcinoma at gastroesophageal junction and tumor long diameter ≤8 cm by gastroscopy and CT, The her-2 negative was detected by immunohistochemistry; Patients with Stage for Ⅲ by CT/MRI (According to the eighth edition of AJCC ); Patients with measurable lesions(measuring≥10mm on spiral CT scan, satisfying the criteria in RECIST1.1); Eastern Cooperative Oncology Group (ECOG) performance status of 0-1; Major organ function has to meet the following certeria: HB≥80g/L; ANC≥1.5×109/L; PLT≥90×109/L; ALT and AST≤2.5×ULN, but<≤5×ULN if the transferanse elevation is due to liver metastases； TBIL<1.5×ULN； Serum creatinine ≤1.5×ULN; Life expectancy greater than or equal to 6 months; 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; Participants were willing to join in this study, and written informed consent, good adherence, cooperate with the follow-up. Exclusion Criteria: Allergic to apatinib, capecitabine and oxaliplatin; The cytological examination of the abdominal cavity washing fluid showed that the tumor shedding cells were positive; Have high blood pressure and antihypertensive drug treatment can not control (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg), Uncontrolled coronary heart disease and arrhythmia ,classⅢ-Ⅳcardiac insufficiency; A variety of factors influencing oral drugs (such as unable to swallow, nausea, vomiting, chronic diarrhea and intestinal obstruction, etc); Patients with tendency of gastrointestinal bleeding, including the following: a local active ulcerative lesions, and defecate occult blood (+ +); Has melena and hematemesis in two months; Coagulant function abnormality (INR > 1.5 ULN, APTT > 1.5 ULN), with bleeding tendency; Pregnant or lactating women; Patients with other malignant tumors within 5 years (except for curable skin basal cell carcinoma and cervical carcinoma in situ); History of psychiatric drugs abuse and can't quit or patients with mental disorders; Less than 4 weeks from the last clinical trial; 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 XELOX and radiotherapy<br>apatinib：250mg qd po XELOX：Capecitabine 1000mg/m2 bid d1-14，Oxaliplatin 130 mg/m2 Ivgtt d1 q3w Radiotherapy：45Gy/25f （1.8Gy/f/d，5 f/w） | Drug: apatinib<br>* apatinib：250mg qd po<br>Drug: Capecitabine<br>* 1000mg/m2 bid d1-14<br>Drug: Oxaliplatin<br>* 130 mg/m2 Ivgtt d1 q3w<br>Radiation: Radiotherapy<br>* 45Gy/25f （1.8Gy/f/d，5 f/w）<br>|
| Active Comparator: XELOX and radiotherapy<br>XELOX：Capecitabine 1000mg/m2 bid d1-14，Oxaliplatin 130 mg/m2 Ivgtt d1 q3w Radiotherapy：45Gy/25f （1.8Gy/f/d，5 f/w） | Drug: Capecitabine<br>* 1000mg/m2 bid d1-14<br>Drug: Oxaliplatin<br>* 130 mg/m2 Ivgtt d1 q3w<br>Radiation: Radiotherapy<br>* 45Gy/25f （1.8Gy/f/d，5 f/w）<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The pathological complete response rate(pCR) | The lesion disappeared completely by pathology | within 3 weeks after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Baseline to measured stable disease | within 3 weeks after surgery | 
| R0-resection rate | There was no residual by the microscope | within 3 weeks after surgery | 
| Disease-free survival(DFS) | Baseline to measured date of recurrence or death from any cause | 3 year | 
| Overall survival (OS) | Baseline to measured date of death from any cause | 3years | 
| Adverse events | Toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.The number of Participants with adverse events will be recorded at each treatment visit. | 3 year |