Preoperative Concurrent Chemoradiotherapy for Potentially Resectable Adenocarcinoma of the Esophagogastric Junction (A-C)

Phase II Multi-Institutional Randomized Trial of Capecitabine Plus Oxaliplatin With Concurrent Radiotherapy in Patients With Potentially Resectable Adenocarcinoma of Gastroesophageal Cancer

Stage I：preoperative therapy

• Capecitabine plus oxaliplatin with concurrent radiotherapy is superior to surgery alone ; Stage II: Perioperative therapy
• Perioperative Capecitabine plus oxaliplatin with Concurrent radiotherapy is superior to adjuvant Capecitabine plus oxaliplatin alone;
• A regimen of Capecitabine plus oxaliplatin(XELOX) improves survival among patients with incurable locally advanced or metastatic adenocarcinoma of stomach and gastroesophageal cancer . The investigators assessed whether the addition of a perioperative regimen of XELOX regimen with concurrent radiotherapy to adjuvant alone improves R0 resection rate and survival among patients with curable locally advanced adenocarcinoma of stomach and gastroesophageal cancer

Study Overview

• Status: Completed
• Conditions: Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: Oxaliplatin; Capecitabine; Other: Oxaliplatin; Capecitabine; concurrent radiotherapy

• Study Type: Interventional
• Enrollment (Actual): 169
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Hebei
    • Shijiazhuang, Hebei, China, 050011
      • Department of General Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Disease must be clinically limited to the esophagogastric junction, defined TypeⅡ TypeⅢ(From the endoscopic point of view according to the AEG criteria)
2. Histologically confirmed primary adenocarcinoma
3. T2-4 N0-3 M0. T1 tumors are eligible if T1N1-3M0，
4. ECOG performance status ≦2

AEG is defined and described as tumors which have their center within 5cm proximal or distal of the anatomical cardia.

The classification of AEG type I, type II and type III AEG type I: adenocarcinoma of the distal esophagus,which usually arises from an area with specialized intestinal metaplasia of the esophagus, i Barrett's esophagus, and may infiltrate the esophago-gastric junction from above;

• AEG type II: true carcinoma of the cardia, arising from the cardia epithelium or short segments with intestinal metaplasia at the esophago-gastric junction;
• AEG type III: subcardial gastric carcinoma, which infiltrates the esophago-gastric junction and distal esophagus from below.

Exclusion Criteria:

1. Tis (in-situ carcinoma) and tumors determined to be TIN0 following endoscopy, endoscopic ultrasound and CT scanning.
2. Patients with primary carcinomas of the esophagus.
3. Prior chest or upper abdomen radiotherapy, prior systemic chemotherapy within the past 5 years, or prior esophageal or gastric surgery.
4. Patients with evidence of metastatic disease are not eligible.
5. Patients with a history of seizure disorder who are receiving phenytoin, phenobarbital, or other antiepileptic medication.
6. Patients who cannot fully comprehend the therapeutic implications of the protocol or comply with its requirements.
7. Patients with any medical or psychiatric condition or disease which, in the investigator's judgment, would make the patient inappropriate for entry into this study.
8. History of hypersensitivity to fluoropyrimidines, capecitabine, oxaliplatin or the ingredients of this product -

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
Active Comparator: postoperative chemotherapy,XELOX	Drug: Oxaliplatin; Capecitabine; Capecitabine 2000mg/m2 D1-D14 q3wk and Oxaliplatin 130 mg/m2 D1 q3wk for eight cycles postoperation; Other Names: Xeloda; Oxaliplatin
Experimental: Preoperative Concurrent Chemoradiotherapy	Other: Oxaliplatin; Capecitabine; concurrent radiotherapy; Capecitabine 2000mg/m2 D1-D14 q3wk and Oxaliplatin 130 mg/m2 D1 q3wk for two cycles preoperation , Capecitabine 2000mg/m2 D1-D14 q3wk and Oxaliplatin 130 mg/m2 D1 q3wk for six cycles postoperation Radiation: radiotherapy 50 Gy in 25 fractions (2Gy /day, 5 days/week,Monday through Friday, ) Other Name: XRT; Other Names: Xeloda; Oxaliplatin; XRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease-free survival(DFS)	3 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)		within 3 weeks after surgery
R0-resection rate		within 3 weeks after surgery
Disease control rate (DCR)		within 3 weeks after surgery
Down-staging Rate		within 3 weeks after surgery
Overall survival (OS)		3years
Adverse events	Side effects during observation] Investigators graded all adverse events and toxic effects according to the National Cancer Institute's Common Toxicity Criteria, version 2.0. The number of Participants with adverse events will be recorded at each treatment visit.	3 year
Death related to operation		4 weeks

Collaborators and Investigators

• Sponsor: Hebei Medical University

Publications and helpful links

General Publications

• Tian Y, Wang J, Qiao X, Zhang J, Li Y, Fan L, Zhang Z, Zhao X, Tan B, Wang D, Yang P, Zhao Q. Long-Term Efficacy of Neoadjuvant Concurrent Chemoradiotherapy for Potentially Resectable Advanced Siewert Type II and III Adenocarcinomas of the Esophagogastric Junction. Front Oncol. 2021 Nov 11;11:756440. doi: 10.3389/fonc.2021.756440. eCollection 2021.

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): February 1, 2020
• Study Completion (Actual): August 1, 2021

Study Registration Dates

• First Submitted: July 22, 2012
• First Submitted That Met QC Criteria: October 10, 2013
• First Posted (Estimate): October 14, 2013

Study Record Updates

• Last Update Posted (Actual): February 21, 2022
• Last Update Submitted That Met QC Criteria: February 4, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Capecitabine; Oxaliplatin; Gastroesophageal Junction Adenocarcinoma; Preoperative Concurrent Chemoradiotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Adenocarcinoma; Esophageal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine; Oxaliplatin
• Other Study ID Numbers: Alien-Craft