A Phase II Study of Total Neoadjuvant Therapy for Locally Advanced Gastric Cancer

This prospective, single arm phase II study is designed to evaluate the rate of pathologic complete response of neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy followed by surgery for locally advanced gastric adenocarcinoma

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer; Neoadjuvant Therapy
• Intervention / Treatment: Drug: SOX; Radiation: SIB-IMRT; Drug: S-1; Procedure: Surgery

• Study Type: Interventional
• Enrollment (Anticipated): 82
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100021
    • Recruiting
    • Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
    • Contact: Ning Li, MD; Phone Number: +8613810381399; Email: lee_ak@163.com
    • Sub-Investigator: Jinming Shi, MD

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 cT3-4N+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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Total Neoadjuvant Chemoradiotherapy; Total neoadjuvant chemoradiotherapy arm receives intensity-modulated neoadjuvant chemoradiotherapy (45Gy in 25 fractions) concurrently with oral S-1(40-60mg/m2, orally twice daily every weekday) followed by six cycles of SOX neoadjuvant chemotherapy and surgery

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); Radiation: SIB-IMRT; 45Gy in 25 fractions using intensity-modulated radiotherapy to the radiation target; Drug: S-1; 40-60mg/m2(according to patient's body surface area), orally twice daily every weekday concurrently with radiotherapy treatment; Procedure: Surgery; Surgery, preferred D2 lymphadenectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PCR 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 telemicroscope. 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).	6-8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
surgery complications	During hospital stay and within the first 30 days after completion of surgery.	6-8 months
Tumor down-staging	Down-staging was considered as any stage reduction between clinical and pathologic stage.	6-8 months
R0 resection rate	The surgical procedure was total or subtotal gastrectomy with recommended D2 lymphadenectomy 4-6 weeks after total neoadjuvant therapy.	6-8 months

Collaborators and Investigators

• Sponsor: Jing Jin, M.D.
• Collaborators: Beijing Hope Run

Publications and helpful links

General Publications

• Li N, Xiang X, Zhao D, Wang X, Tang Y, Chi Y, Yang L, Jiang L, Jiang J, Shi J, Liu W, Fang H, Tang Y, Chen B, Lu N, Jing H, Qi S, Wang S, Liu Y, Song Y, Li Y, Zhang L, Jin J. Preoperative versus postoperative chemo-radiotherapy for locally advanced gastric cancer: a multicenter propensity score-matched analysis. BMC Cancer. 2022 Feb 26;22(1):212. doi: 10.1186/s12885-022-09297-7.
• Shi J, Li N, Tang Y, Jiang L, Yang L, Wang S, Song Y, Liu Y, Fang H, Lu N, Qi S, Chen B, Li Z, Liu S, Wang J, Wang W, Zhu S, Yang J, Li Y, Zhao D, Jin J. Total neoadjuvant therapy for locally advanced gastric cancer and esophagogastric junction adenocarcinoma: study protocol for a prospective, multicenter, single-arm, phase II clinical trial. BMC Gastroenterol. 2022 Jul 28;22(1):359. doi: 10.1186/s12876-022-02440-5.

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2019
• Primary Completion (Anticipated): September 21, 2022
• Study Completion (Anticipated): September 21, 2023

Study Registration Dates

• First Submitted: August 18, 2019
• First Submitted That Met QC Criteria: August 18, 2019
• First Posted (Actual): August 20, 2019

Study Record Updates

• Last Update Posted (Actual): January 24, 2022
• Last Update Submitted That Met QC Criteria: January 20, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: neoadjuvant chemotherapy; gastric cancer; neoadjuvant chemoradiotherapy
• 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: LC2018L03

Drug and device information, study documents

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