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

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.

Study Overview

• Status: Unknown
• Conditions: Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: Oxaliplatin; Drug: apatinib; Drug: Capecitabine; Radiation: Radiotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Qun Zhao; Phone Number: 13930162111; Email: Zhaoqun516@126.com

Study Locations

• China
  • Hebei
    • ShiJiaZhuang, Hebei, China
      • Recruiting
      • The Fourth Hospital of Hebei Medical University
      • Contact: Qun Zhao; Phone Number: 13930162111; Email: Zhaoqun516@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age:18 to 70 years old (man or female);
2. 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;
3. Patients with Stage for Ⅲ by CT/MRI (According to the eighth edition of AJCC );
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 0-1;

6. 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;

7. Life expectancy greater than or equal to 6 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. Participants were willing to join in this study, and written informed consent, good adherence, cooperate with the follow-up.

Exclusion Criteria:

1. Allergic to apatinib, capecitabine and oxaliplatin;
2. The cytological examination of the abdominal cavity washing fluid showed that the tumor shedding cells were positive;
3. 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;
4. A variety of factors influencing oral drugs (such as unable to swallow, nausea, vomiting, chronic diarrhea and intestinal obstruction, etc);
5. 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;
6. Coagulant function abnormality (INR > 1.5 ULN, APTT > 1.5 ULN), with bleeding tendency;
7. Pregnant or lactating women;
8. Patients with other malignant tumors within 5 years (except for curable skin basal cell carcinoma and cervical carcinoma in situ);
9. History of psychiatric drugs abuse and can't quit or patients with mental disorders;
10. Less than 4 weeks from the last clinical trial;
11. The researchers think inappropriate.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: apatinib XELOX and radiotherapy; 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: Oxaliplatin; 130 mg/m2 Ivgtt d1 q3w; Drug: apatinib; apatinib：250mg qd po; Drug: Capecitabine; 1000mg/m2 bid d1-14; Radiation: Radiotherapy; 45Gy/25f （1.8Gy/f/d，5 f/w）
Active Comparator: XELOX and radiotherapy; 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: Oxaliplatin; 130 mg/m2 Ivgtt d1 q3w; Drug: Capecitabine; 1000mg/m2 bid d1-14; Radiation: Radiotherapy; 45Gy/25f （1.8Gy/f/d，5 f/w）

What is the study measuring?

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
R0-resection rate	There was no residual by the microscope	within 3 weeks after surgery
Overall survival (OS)	Baseline to measured date of death from any cause	3years
Objective response rate (ORR)	Baseline to measured stable disease	within 3 weeks after surgery
Disease-free survival(DFS)	Baseline to measured date of recurrence or death from any cause	3 year
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

Collaborators and Investigators

• Sponsor: Hebei Medical University
• Investigators: Principal Investigator: Qun Zhao, Hebei Medical University Fourth Hospital; Principal Investigator: Jun Wang, Hebei Medical University Fourth Hospital

Publications and helpful links

General Publications

• Guo H, Li Y, Lin C, Cheng Y, Zhang Z, Wang D, Zhao X, Liu Y, Jing S, Yang P, Tian Y, Liu Y, Wang J, Zhao Q. Efficacy and safety of neoadjuvant chemoradiotherapy plus apatinib for patients with locally advanced, HER2-negative, Siewert's type II-III adenocarcinoma of esophagogastric junction: a single-arm, open-label, phase II trial. Am J Transl Res. 2021 Aug 15;13(8):9015-9023. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2017
• Primary Completion (Actual): November 30, 2019
• Study Completion (Anticipated): November 30, 2020

Study Registration Dates

• First Submitted: November 17, 2017
• First Submitted That Met QC Criteria: November 17, 2017
• First Posted (Actual): November 22, 2017

Study Record Updates

• Last Update Posted (Actual): February 19, 2020
• Last Update Submitted That Met QC Criteria: February 18, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Protein Kinase Inhibitors; Capecitabine; Oxaliplatin; Apatinib
• Other Study ID Numbers: HRA-G01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No