Neoadjuvant Chemoradiotherapy vs. Chemotherapy With Radical Gastrectomy and Adjuvant Chemotherapy for Advanced Gastric Cancer (Neo-CRAG)

An Randomized, Multicenter, Open-label, Phase III Trial Comparing Neoadjuvant Chemoradiotherapy Versus Chemotherapy in Patients With Locally Advanced Gastric Adenocarcinoma

Patients with histologically confirmed gastric adenocarcinoma with locally advanced gastric cancer are randomized in a 1:1 ratio to receive neoadjuvant chemoradiotherapy with DT45Gy/25f plus three cycles of XELOX therapy or neoadjuvant chemotherapy alone using XELOX regimen following D2 gastrectomy and adjuvant chemotherapy for 3 cycles. The primary end point is disease free survival (DFS), and secondary end point is 5-year overall survival (OS), pathological complete remission (pCR) and treatment safety.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Radiation: Neoadjuvant Chemoradiotherapy; Procedure: R0 D2 Gastrectomy; Drug: Adjuvant Chemotherapy; Drug: Neoadjuvant Chemotherapy

Detailed Description

Background: Literatures have shown that patitents with locally advanced gastric cancer could potentially benefit from neoadjuvant chemoradiotherapy, but whether this can improve patitents' outcome is still unclear.

Patients and methods: In this study , patients with histologically confirmed gastric adenocarcinoma with pre-operative staging are cT3N2/N3M0, cT4aN+M0 and cT4bNanyM0, aged between 18-75 years old, with adequate organ function and having an Eastern Cooperative Oncology Group performance status score ≤2, are randomized in a 1:1 ratio to receive neoadjuvant chemoradiotherapy with DT45Gy/25f plus three cycles of XELOX therapy (Capecitabine 1000mg/m2, BID, D1-14; Oxaliplatin 130mg/m2 on day 1 for a 21-day cycle) or neoadjuvant chemotherapy alone using XELOX regimen following by D2 gastrectomy and adjuvant chemotherapy with same dosage of XELOX therapy for up to 3 cycles. The primary end point is disease free survival (DFS), and secondary end point is 5-year overall survival (OS), pathological complete remission (pCR) and treatment safety. The final study analytics are to be conducted at the end of the 5th year after the last patient's enrollment.

• Study Type: Interventional
• Enrollment (Anticipated): 620
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Zhi-wei Zhou, M.D, Ph.D; Phone Number: 0086-20-87343626; Email: zhouzhw@sysucc.org.cn
• Study Contact Backup: Name: Wei Wang, M.D, Ph.D; Phone Number: 0086-20-87343910; Email: wangwei@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-Sen University Cancer Center
      • Contact: Wei Wang, M.D, Ph.D; Phone Number: 0086-20-87343910; Email: wangwei@sysucc.org.cn
      • Principal Investigator: Zhi-wei Zhou, MD,PhD

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:

• informed consensus of the enrolled patients
• being able to receive oral drug
• from 18 to 75 years old
• proven to be primary adenocarcinoma of gastric cancer and pre-operative staging cT3N2/N3M0, cT4aN+M0, cT4bNanyM0,
• no prior other chemotherapy and/or radiation against the disease
• normal function of all other vital organs including heart,liver ,kidney and so on
• Eastern Cooperative Oncology Group performance status: 0~2

Exclusion Criteria:

• history of other malignancy
• allergic reaction to capecitabine or oxaliplatin
• enrolled in other clinical trials
• abnormal GI tract function
• dysfunction of other organs
• pregnant or lactating females ,or refuse to receive contraception measures during chemotherapy
• other situations judged as not adaptive to the study by investigators

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: Neoadjuvant Chemoradiotherapy; Radiotherapy (45Gy/25f) + 3 cycles of XELOX Chemotherapy (Capecitabine 1000mg/m2, d1-14 + Oxaliplatin 130mg/m2 D1; 21-days/cycle) following with D2 Gastrectomy and 3 cycles of Adjuvant XELOX Chemotherapy	Radiation: Neoadjuvant Chemoradiotherapy; Radiotherapy (45Gy/25f) + 3 cycles of XELOX Chemotherapy (Capecitabine 1000mg/m2, d1-14 + Oxaliplatin 130mg/m2 d1; 21-days/cycle); Procedure: R0 D2 Gastrectomy; Drug: Adjuvant Chemotherapy; 3 cycles of XELOX Chemotherapy (Capecitabine 1000mg/m2, d1-14 + Oxaliplatin 130mg/m2 d1; 21-days/cycle)
Active Comparator: Neoadjuvant Chemotherapy; 3 cycles of XELOX Chemotherapy (Capecitabine 1000mg/m2, d1-14 + Oxaliplatin 130mg/m2 D1; 21-days/cycle) following with D2 Gastrectomy and 3 cycles of Adjuvant XELOX Chemotherapy	Procedure: R0 D2 Gastrectomy; Drug: Adjuvant Chemotherapy; 3 cycles of XELOX Chemotherapy (Capecitabine 1000mg/m2, d1-14 + Oxaliplatin 130mg/m2 d1; 21-days/cycle); Drug: Neoadjuvant Chemotherapy; 3 cycles of XELOX Chemotherapy (Capecitabine 1000mg/m2, d1-14 + Oxaliplatin 130mg/m2 d1; 21-days/cycle)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free Survival	3-year DFS	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	5-year Overall Survival	5 years
Pathological Complete Remission	pCR	Peri-operative period
Radical Resection Rate	R0 Resection Rate	Peri-operative period
Adverse effects	Treatment safety	Peri-operative period

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Zhejiang Cancer Hospital; First People's Hospital of Hangzhou; The First Affiliated Hospital of Anhui Medical University; Guangdong Provincial Hospital of Traditional Chinese Medicine; Guangdong Provincial People's Hospital; First Hospital of China Medical University; Tianjin Medical University Cancer Institute & Hospital; Liaoning Cancer Hospital & Institute; Guangxi Medical University Cancer Center
• Investigators: Principal Investigator: Zhi-wei Zhou, M.D, Ph.D, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2013
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: March 19, 2013
• First Submitted That Met QC Criteria: March 20, 2013
• First Posted (Estimate): March 21, 2013

Study Record Updates

• Last Update Posted (Actual): August 31, 2018
• Last Update Submitted That Met QC Criteria: August 29, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Chemotherapy; Neoadjuvant; Chemoradiotherapy; Pathological complete response; Locally advanced gastric cancer; D2 gastrectomy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: SYSUCCGPS2