Apatinib Plus Concurrent Neoadjuvant Chemoradiotherapy for Gastroesophageal Junction

Prospective, Randomized, Controlled, Multicenter, Phase III 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: Apatinib Capecitabine Oxaliplatin; Drug: Capecitabine Oxaliplatin

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Hebei
    • Shijia Zhuang, Hebei, China
      • Recruiting
      • QunZhao
      • Contact: Qun Zhao; Phone Number: 8613930162111; Email: zhaoqun@hebmu.edu.cn

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. Adult patients (18 to 70 years old) at the time of voluntarily signing informed consent;
2. Histologically or cytologically confirmed adenocarcinoma. The her-2 negative was detected by immunohistochemistry or fluorescence in situ hybridization;
3. Confirmed to Siewert II , III of locally advanced adenocarcinoma at gastroesophageal junction and tumor long diameter ≤8 cm by gastroscopy;
4. Patients with Stage for Ⅲ by CT/MRI (According to the eighth edition of AJCC );
5. Patients with measurable lesions(measuring≥10mm on spiral CT scan, satisfying the criteria in RECIST1.1);
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
7. Life expectancy greater than or equal to 6 months;
8. Subject must meet all of the following criteria based on the laboratory tests within 14 days prior to the first dose of study treatment.

(1) Baseline blood indicators meet the following criteria:HB≥80g/L;ANC≥1.5×109/L;PLT≥90×109/L;WBC≥4.0×109/L and ≤15×109/L (2) Baseline biochemical indicators meet the following criteria: ALT and AST≤2.5ULN, but<≤5ULN if the transferanse elevation is due to liver metastases; ALP≤2.5ULN;TBiL≤1.5ULN；Cr≤1.5ULN,Endogenous creatinine clearance rate ˃60 ml/min (Cockcroft-Gault formula);APTT≤1.5ULN,and INR or PT≤1.5ULN.

9.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; 10.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: A(apatinib Xelox); Preoperative: apatinib 250mg qd po q4w Capecitabine 1000mg/m2 bid d1-14，Oxaliplatin 130 mg/m2 Ivgtt d1 q3w Radiotherapy：45Gy/25f （1.8Gy/f/d，5 f/w） Postoperative: Capecitabine 1000mg/m2 bid d1-14 q3w 2 cycles	Drug: Apatinib Capecitabine Oxaliplatin; apatinib 250mg qd po q4w Capecitabine 1000mg/m2 bid d1-14，Oxaliplatin 130 mg/m2 Ivgtt d1 q3w
Active Comparator: B(Xelox); Preoperative: Capecitabine 1000mg/m2 bid d1-14，Oxaliplatin 130 mg/m2 Ivgtt d1 q3w Radiotherapy：45Gy/25f （1.8Gy/f/d，5 f/w） Postoperative: Capecitabine 1000mg/m2 bid d1-14 q3w 6 cycles	Drug: Capecitabine Oxaliplatin; Preoperative: Capecitabine 1000mg/m2 bid d1-14，Oxaliplatin 130 mg/m2 Ivgtt d1 q3w

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	[ Time Frame: within 3 weeks after surgery ]
Disease-free survival(DFS)	Baseline to measured date of recurrence or death from any cause	[ Time Frame: 3 year ]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Baseline to measured stable disease	[ Time Frame: Preoperative ]
Disease Control Rate（DCR）	Baseline to measured disease progression	[ Time Frame: Preoperative ]
R0-resection rate	There was no residual by the microscope	[ Time Frame: within 3 weeks after surgery ]
Overall survival (OS)	Baseline to measured date of death from any cause	[ Time Frame: 3years ]

Collaborators and Investigators

• Sponsor: Hebei Medical University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Anticipated): June 30, 2020
• Study Completion (Anticipated): January 31, 2021

Study Registration Dates

• First Submitted: June 11, 2019
• First Submitted That Met QC Criteria: June 11, 2019
• First Posted (Actual): June 14, 2019

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-G04

Drug and device information, study documents

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