A Randomized Phase II Trial of Neoadjuvant Chemotherapy Compared With Chemoradiotherapy in Gastric Adenocarcinoma

A Prospective, Randomized Phase II Trial of Neoadjuvant Chemotherapy Compared With Concomitant Boost Intensity-Modulated Radiotherapy With S-1 in Locally Advanced Gastric Adenocarcinoma

This prospective, randomized phase II study is designed to evaluate weather neoadjuvant chemoradiotherapy is superior to neoadjuvant chemotherapy with both followed by surgery and postoperative chemotherapy for locally advanced gastric adenocarcinoma.

Study Overview

• Status: Completed
• Conditions: Stomach Neoplasms; Chemotherapy; Neoadjuvant Therapy; Chemoradiotherapy
• Intervention / Treatment: Drug: SOX; Procedure: Surgery; Radiation: SIB-IMRT; Drug: S-1

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100021
    • Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)

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:

• Histologically or cytologically proven locally advanced gastric adenocarcinoma in patients staged as cT3-4N0M0 or anyTN+M0
• No distant metastasis in liver,lung,bone,central nervous system(CNS),no peritoneal transplantation
• No prior abdominal or pelvic radiotherapy
• Karnofsky performance status(KPS)≥ 70, predictive life span no less than 6 months
• Patients must have normal organ and marrow function as defined below: Leukocytes: greater than or equal to 3,000 G/L; Platelets: greater than or equal to 100,000/mm3 .Hemoglobin:greater than or equal to 10g/L .Total bilirubin: within normal institutional limits; AST/ALT: less than or equal to 1.5 times the upper limit; Creatinine within normal upper limits
• Informed consent

Exclusion Criteria:

• Any prior chemotherapy or other cancer treatment prior to this protocol
• Patients with other cancer history except cervical carcinoma in situ and non-malignant melanoma skin cancer
• With any distant metastasis in liver,lung,bone,CNS,or peritoneal transplantation
• History of allergic reactions attributed to similar chemical or biologic complex to S-1 or Xeloda or Oxaliplatin
• Uncontrolled illness including, but not limited to, active infection, symptomatic heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness
• History of myocardial infarction within the past 6 months or history of ventricular arrhythmia
• History of prior radiation to the abdomen
• Pregnant or lactating females

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 (NCRT); NCRT arm receives intensity-modulated radiotherapy with a simultaneous integrated boost (SIB-IMRT) (45.1Gy and 40.04Gy in 22 fractions) concurrently with oral S-1(40mg/m2, orally twice daily every weekday) followed by surgery and four to six cycles of SOX at the same dosage with NCT arm.	Drug: SOX; SOX (S-1: 40~60mg, orally twice daily on days 1 to 14, oxaliplatin 130mg/m2 intravenously on day 1, 21 days per cycle); Other Names: TS-1; Oxaliplatin for injection; Procedure: Surgery; Surgery, preferred D2 lymphadenectomy; Radiation: SIB-IMRT; 45.1Gy and 40.04Gy in 22 fractions using intensity-modulated radiotherapy with a simultaneous integrated boost (SIB-IMRT) to primary tumor; Drug: S-1; 40mg/m2, orally twice daily every weekday concurrently with radiotherapy treatment; Other Names: TS-1
Active Comparator: Neoadjuvant Chemotherapy (NCT); NCT arm consists of neoadjuvant three cycles of SOX(S-1: 40~60mg, orally twice daily on days 1 to 14, oxaliplatin 130mg/m2 intravenously on day 1, 21 days per cycle followed by radical surgery and another postoperative three cycles of SOX.	Drug: SOX; SOX (S-1: 40~60mg, orally twice daily on days 1 to 14, oxaliplatin 130mg/m2 intravenously on day 1, 21 days per cycle); Other Names: TS-1; Oxaliplatin for injection; Procedure: Surgery; Surgery, preferred D2 lymphadenectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 resection rate	The surgical procedure was total or subtotal gastrectomy with recommended D2 lymphadenectomy 4-6 weeks after neoadjuvant therapy.	2-3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		3 years
Distant metastasis free survival		3 years
Locoregional recurrence free survival		3 years
Acute chemotherapy/Chemoradiotherapy toxicities	chemotherapy toxicities are evaluated by NCI-CTC version 4.0 and radiotherapy toxicities are graded using the RTOG/EORTC Radiation Morbidity Scoring Schema.	6-8 months
Pathological response rate	Pathological response were classified into three grades.Grade I signifies that there is little shrinkage in the tumor; only mild regression in the tumor cells is observed under themicroscope. Grade II shows gross reduction in size of the tumor and marked regression in the cancer cells microscopically, yet viable nests of cancer tissue are still visible. Grade III implies complete or almost total resolution of the tumor on exploration, and disappearance of the tumor tissue microscopically; only remnants of degenerated cancer cells can be seen (so-called ghost cancer cells).	2-3 months
Tumor down-staging	Down-staging was considered as any stage reduction between clinical and pathologic stage.	2-3 months
Postoperative complications	During hospital stay and within the first 30 days after completion of surgery.	2-3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of dosimetric differences between radiation techniques	To compare the dosimetric differences between the volumetric-modulated arc therapy (VMAT), Tomotherapy and intensity-modulated radiotherapy (IMRT) techniques in treatment planning.	1 year

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Publications and helpful links

General Publications

• Wang X, Zhao DB, Yang L, Chi Y, Zhao H, Jiang LM, Jiang J, Tang Y, Li N, Liu WY, Dou LZ, Zou SM, Xue LY, Ren JS, Tian YT, Che X, Guo CG, Bai XF, Sun YM, Wang SL, Song YW, Liu YP, Fang H, Li YX, Jin J. Preoperative Concurrent Chemoradiotherapy Versus Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer: Phase II Randomized Study. Front Oncol. 2022 Apr 29;12:870741. doi: 10.3389/fonc.2022.870741. eCollection 2022.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: November 23, 2014
• First Submitted That Met QC Criteria: November 23, 2014
• First Posted (Estimate): November 26, 2014

Study Record Updates

• Last Update Posted (Actual): October 16, 2019
• Last Update Submitted That Met QC Criteria: October 15, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• 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; Stomach Diseases; Stomach Neoplasms; Adenocarcinoma; Antineoplastic Agents; Oxaliplatin
• Other Study ID Numbers: NCC2015ST-09