A Randomized Phase II Trial of Neoadjuvant Chemotherapy Compared With Chemoradiotherapy in Gastric Adenocarcinoma
Primary Purpose
Stomach Neoplasms, Neoadjuvant Therapy, Chemoradiotherapy
Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
SIB-IMRT
S-1
Surgery
SOX
Sponsored by
About this trial
This is an interventional treatment trial for Stomach Neoplasms
Eligibility Criteria
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
Sites / Locations
- Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Neoadjuvant Chemoradiotherapy (NCRT)
Neoadjuvant Chemotherapy (NCT)
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
R0 resection rate
The surgical procedure was total or subtotal gastrectomy with recommended D2 lymphadenectomy 4-6 weeks after neoadjuvant therapy.
Secondary Outcome Measures
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).
Tumor down-staging
Down-staging was considered as any stage reduction between clinical and pathologic stage.
Postoperative complications
During hospital stay and within the first 30 days after completion of surgery.
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.
Distant metastasis free survival
Locoregional recurrence free survival
Overall survival
Full Information
NCT ID
NCT02301481
First Posted
November 23, 2014
Last Updated
October 15, 2019
Sponsor
Chinese Academy of Medical Sciences
1. Study Identification
Unique Protocol Identification Number
NCT02301481
Brief Title
A Randomized Phase II Trial of Neoadjuvant Chemotherapy Compared With Chemoradiotherapy in Gastric Adenocarcinoma
Official Title
A Prospective, Randomized Phase II Trial of Neoadjuvant Chemotherapy Compared With Concomitant Boost Intensity-Modulated Radiotherapy With S-1 in Locally Advanced Gastric Adenocarcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
January 2014 (undefined)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
December 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese Academy of Medical Sciences
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stomach Neoplasms, Neoadjuvant Therapy, Chemoradiotherapy, Chemotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
71 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Neoadjuvant Chemoradiotherapy (NCRT)
Arm Type
Experimental
Arm Description
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.
Arm Title
Neoadjuvant Chemotherapy (NCT)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Radiation
Intervention Name(s)
SIB-IMRT
Intervention Description
45.1Gy and 40.04Gy in 22 fractions using intensity-modulated radiotherapy with a simultaneous integrated boost (SIB-IMRT) to primary tumor
Intervention Type
Drug
Intervention Name(s)
S-1
Other Intervention Name(s)
TS-1
Intervention Description
40mg/m2, orally twice daily every weekday concurrently with radiotherapy treatment
Intervention Type
Procedure
Intervention Name(s)
Surgery
Intervention Description
Surgery, preferred D2 lymphadenectomy
Intervention Type
Drug
Intervention Name(s)
SOX
Other Intervention Name(s)
TS-1; Oxaliplatin for injection
Intervention Description
SOX (S-1: 40~60mg, orally twice daily on days 1 to 14, oxaliplatin 130mg/m2 intravenously on day 1, 21 days per cycle)
Primary Outcome Measure Information:
Title
R0 resection rate
Description
The surgical procedure was total or subtotal gastrectomy with recommended D2 lymphadenectomy 4-6 weeks after neoadjuvant therapy.
Time Frame
2-3 months
Secondary Outcome Measure Information:
Title
Pathological response rate
Description
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).
Time Frame
2-3 months
Title
Tumor down-staging
Description
Down-staging was considered as any stage reduction between clinical and pathologic stage.
Time Frame
2-3 months
Title
Postoperative complications
Description
During hospital stay and within the first 30 days after completion of surgery.
Time Frame
2-3 months
Title
Acute chemotherapy/Chemoradiotherapy toxicities
Description
chemotherapy toxicities are evaluated by NCI-CTC version 4.0 and radiotherapy toxicities are graded using the RTOG/EORTC Radiation Morbidity Scoring Schema.
Time Frame
6-8 months
Title
Distant metastasis free survival
Time Frame
3 years
Title
Locoregional recurrence free survival
Time Frame
3 years
Title
Overall survival
Time Frame
3 years
Other Pre-specified Outcome Measures:
Title
Comparison of dosimetric differences between radiation techniques
Description
To compare the dosimetric differences between the volumetric-modulated arc therapy (VMAT), Tomotherapy and intensity-modulated radiotherapy (IMRT) techniques in treatment planning.
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
City
Beijing
ZIP/Postal Code
100021
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
35574368
Citation
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.
Results Reference
derived
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A Randomized Phase II Trial of Neoadjuvant Chemotherapy Compared With Chemoradiotherapy in Gastric Adenocarcinoma
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