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

A Randomized, Open-Label, Multicenter, Controlled Phase III Trial Comparing Neoadjuvant Chemoradiotherapy Followed by Surgery and Adjuvant Chemotherapy Versus Neoadjuvant Chemotherapy Followed by Surgery and Adjuvant Chemotherapy in Patients With Locally Advanced Gastric Cancer

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 3-year disease free survival (DFS), and secondary end point is 5-year overall survival (OS), R0 resection rate, pathological complete remission (pCR) and treatment safety.

Study Overview

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

Detailed Description

Background: Literatures have shown that patients with locally advanced gastric cancer could potentially benefit from neoadjuvant chemoradiotherapy, but whether this can improve patients' 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 [Oxaliplatin 130 mg/m² IV on Day 1 + Capecitabine 1000 mg/m² orally BID on Days 1-14 of a 21-day cycle (non-concurrent); Oxaliplatin 100 mg/m² IV on Day 1 + Capecitabine 825 mg/m² orally BID on Days 1-14 of a 21-day cycle (concurrent chemoradiotherapy)] or neoadjuvant chemotherapy alone using XELOX regimen (Oxaliplatin 130 mg/m² IV on Day 1 + Capecitabine 1000 mg/m² orally BID on Days 1-14 of a 21-day cycle) following by D2 gastrectomy and adjuvant chemotherapy with same dosage of XELOX therapy for up to 3 cycles. The primary end point is 3-year disease free survival (DFS), and secondary end point is 5-year overall survival (OS), R0 resection rate, 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 (Actual): 620
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Histologically confirmed gastric cancer with clinical staging determined by endoscopic ultrasound and contrast-enhanced CT or MRI as cT3N2/N3M0, cT4aN+M0, or cT4bNanyM0.
2. Good general condition, with Eastern Cooperative Oncology Group (ECOG) performance status <2 and no contraindications to surgery.
3. Ambulatory male or female patients aged 18 to 75 years.
4. Sufficient physical fitness and organ function to tolerate major abdominal surgery.
5. Baseline laboratory parameters meeting the following criteria: WBC > 4.0 × 10⁹/L, ANC > 1.5 × 10⁹/L, Hb ≥ 100 g/L, PLT ≥ 100 × 10⁹/L, total bilirubin ≤ 1.5 × upper limit of normal (ULN), AST and ALT ≤ 2.5 × ULN, and serum creatinine ≤ 1.0 × ULN.
6. No prior or concurrent diagnosis of other malignancies.
7. Willing and able to comply with study protocol requirements during the trial period.
8. Provided written informed consent prior to screening, with full awareness of the right to withdraw from the study at any time without consequence.
9. Estimated life expectancy of at least 3 months.

Exclusion Criteria:

1. Pregnant or breastfeeding women, or women of childbearing potential not using effective contraception.
2. Receipt of any antitumor therapy prior to surgery.
3. History of or concurrent malignancies other than gastric cancer.
4. Presence of psychiatric disorders, brain metastases, or leptomeningeal metastases.
5. Uncontrolled or severe comorbid conditions or active infections.
6. Decompensated dysfunction of major organs (e.g., cardiac, pulmonary, hepatic, or renal failure).
7. Concurrent participation in another clinical trial.
8. Contraindications to chemotherapy, radiotherapy, or surgery.
9. Active hepatitis B or hepatitis C virus infection.
10. Grade ≥2 peripheral neuropathy (per NCI-CTCAE).
11. Chronic intestinal diseases or short bowel syndrome.
12. Known dihydropyrimidine dehydrogenase (DPD) deficiency.
13. Known hypersensitivity to capecitabine or any of its excipients.
14. Ongoing treatment with sorivudine or related analogs.
15. Deemed unsuitable for participation in this clinical trial by the investigator.

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 [Oxaliplatin 130 mg/m² IV on Day 1 + Capecitabine 1000 mg/m² orally BID on Days 1-14 of a 21-day cycle (non-concurrent); Oxaliplatin 100 mg/m² IV on Day 1 + Capecitabine 825 mg/m² orally BID on Days 1-14 of a 21-day cycle (concurrent chemoradiotherapy) ] following with D2 Gastrectomy and 3 cycles of Adjuvant XELOX Chemotherapy	Procedure: R0 D2 Gastrectomy; Radiation: Neoadjuvant Chemoradiotherapy; Radiotherapy (45Gy/25f) + 3 cycles of XELOX Chemotherapy [Oxaliplatin 130 mg/m² IV on Day 1 + Capecitabine 1000 mg/m² orally BID on Days 1-14 of a 21-day cycle (non-concurrent); Oxaliplatin 100 mg/m² IV on Day 1 + Capecitabine 825 mg/m² orally BID on Days 1-14 of a 21-day cycle (concurrent chemoradiotherapy)]; Drug: Adjuvant Chemotherapy; 3 cycles of XELOX Chemotherapy (Oxaliplatin 130 mg/m² IV on Day 1 + Capecitabine 1000 mg/m² orally BID on Days 1-14 of a 21-day cycle)
Active Comparator: Neoadjuvant Chemotherapy; 3 cycles of XELOX Chemotherapy (Oxaliplatin 130 mg/m² IV on Day 1 + Capecitabine 1000 mg/m² orally BID on Days 1-14 of a 21-day cycle) following with D2 Gastrectomy and 3 cycles of Adjuvant XELOX Chemotherapy	Procedure: R0 D2 Gastrectomy; Drug: Adjuvant Chemotherapy; 3 cycles of XELOX Chemotherapy (Oxaliplatin 130 mg/m² IV on Day 1 + Capecitabine 1000 mg/m² orally BID on Days 1-14 of a 21-day cycle); Drug: Neoadjuvant Chemotherapy; 3 cycles of XELOX Chemotherapy (Oxaliplatin 130 mg/m² IV on Day 1 + Capecitabine 1000 mg/m² orally BID on Days 1-14 of a 21-day 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; The First Affiliated Hospital of Anhui Medical University; Guangdong Provincial Hospital of Traditional Chinese Medicine; The Affiliated Hospital of Qingdao University; Tianjin Medical University Cancer Institute and Hospital; Guangdong Provincial People's Hospital; First Hospital of China Medical University; Sichuan Cancer Hospital and Research Institute; Hangzhou First People's Hospital, School of Medicine, Zhejiang Universiry; Liaoning Cancer Hospital & Institute; The Affiliated Tumor Hospital of Guangxi Medical University; National Clinical Research Center for Cancer/Cancer Hospital
• 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 (Actual): June 1, 2025
• Study Completion (Actual): June 1, 2025

Study Registration Dates

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

Study Record Updates

• Last Update Posted (Actual): July 3, 2025
• Last Update Submitted That Met QC Criteria: June 30, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No