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出境医 / 临床实验 / S-1 for 9 Months Versus 1 Year for Stage II Gastric Cancer (SMAC)

S-1 for 9 Months Versus 1 Year for Stage II Gastric Cancer (SMAC)

Study Description
Brief Summary:

The study aims to compare the efficacy and safety of S-1 for 9 months versus S-1 for 1 year as adjuvant chemotherapy after D2 resection in patients with gastric cancer.

Hypothesis: For gastric patients after D2 resection, S-1 for 9 months shows non-inferiority to S-1 for 1 year in disease-free survival(DFS), overall survival (OS) and safety.


Condition or disease Intervention/treatment Phase
Gastric Cancer Drug: S-1 for 9 months Drug: S-1 for 1 year Phase 3

Detailed Description:

It has been identified that S-1 is an effective adjuvant treatment for East Asian patients who have undergone a D2 dissection for locally advanced gastric cancer(GC) in the Japanese Adjuvant Chemotherapy Trial of TS-1(S-1) for Gastric Cancer (ACTS-GC) trail, And S-1 has become one of the standard therapies to these patients. But it is still unknown whether it would improve equally or even more to overall survival(OS) and disease-free survival(DFS) than S-1 for 1 year compared with S-1 for 9 months. As a result, An further clinical trial is still needed, This trial is designed to investigate the efficacy and safety of S-1 for 9 months versus S-1 for 1 year as adjuvant chemotherapy after D2 resection in patients with gastric cancer.

In this study, patients histologically confirmed stage II and who received D2 resection were randomly assigned to receive S-1 for 9 months or S-1 for 1 year. Patients aged from 18 to 75 years and adequate organ function are randomized 1:1 to S-1 for 9 months and S-1 for 1 year. Both are the 3-week recycle of S-1 (80-120mg per day) for 2 weeks, followed by 1 week of rest. The primary endpoint is 3-year DFS, and the secondary endpoint is 5-year OS and safety. Final study analysis will be conducted at the end of the 5th year after the last patient's enrollment. In summary, we hold the hypothesis that S-1 for 9 months is equally effective, safer, and easier to carry out. If possible, there will be a new adjuvant chemotherapy strategy for gastric cancer patients after D2 resection.

To ensure the quality of the study, two interim analyses will be planned at the half and the completion of the study respectively. The DATA and Safety Monitoring Committee will independently review the interim analysis and stop the study ahead of schedule if necessary. Furthermore, to improve the study progress and quality, the in-house interim monitoring will be performed.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1006 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Compare S-1 for 9 Months to 1 Year as Adjuvant Chemotherapy in Stage II Gastric Cancer (SMAC)
Actual Study Start Date : January 1, 2019
Estimated Primary Completion Date : January 1, 2022
Estimated Study Completion Date : May 1, 2027
Arms and Interventions
Arm Intervention/treatment
Experimental: S-1 for 9 months
S-1 80-120mg daily for 14 days in 3 weeks for totally 9 months after D2 resection
Drug: S-1 for 9 months
S-1 for 9 months after D2 resection
Other Name: Tegafur,Gimeracil and Oteracil Porassium Capsules

Active Comparator: S-1 for 1 year
S-1 80-120mg daily for 14 days in 3 weeks for totally 1 year after D2 resection
Drug: S-1 for 1 year
S-1 for 1 year after D2 resection
Other Name: Tegafur,Gimeracil and Oteracil Porassium Capsules

Outcome Measures
Primary Outcome Measures :
  1. DFS [ Time Frame: 3-year ]
    Disease-free survival


Secondary Outcome Measures :
  1. OS [ Time Frame: 5-year ]
    Overall survival


Other Outcome Measures:
  1. Side effects [ Time Frame: 1-year ]
    Complications such as Nausea, vomiting, myelosuppression, and Liver or kidney function disorder


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. The lower age limit of research subjects 18 years old and upper age limit of 75 years old.
  2. Be proven to be primary adenocarcinoma of gastric cancer and staged II by pathological evidence
  3. R0 surgery with lymphadenectomy
  4. Without any other malignancies
  5. ECOG (ECOG score standard) performance status of 0 or 1 and expected to survive more than 6 months
  6. No contraindications to chemotherapy, including normal peripheral blood routine, liver, and kidney function and electrocardiogram (WBC≥4.0 x 109 /L, NEU≥1.5 x 109 /L, PLT≥100 x 109 /L and HGB≥90g/L).

Exclusion Criteria:

  1. Female in pregnancy or lactation, or refuse to receive Contraception measures during chemotherapy.
  2. Patients with stage I, III and IV.
  3. Unavailable for R0 resection and D2 lymph node dissection.
  4. Suffering from other uncontrolled diseases, such as other tumors, acute and Chronic infection.
  5. With severe heart disease, including congestive heart failure, uncontrolled arrhythmias, unstable angina, myocardial infarction, severe heart valve disease, and resistant hypertension.
  6. Any Known or suspected history of drug allergy test.
  7. The researchers believe the patient is not able to complete the entire course of the experiment.
  8. Patients (within 4 weeks) are receiving any other anti-cancer drugs therapy, biological therapy, radiation therapy, or Immunosuppressive therapy.
  9. Patients conform to any of the following: post-organ transplant, necessary for long-term immunosuppressive or suffering with autoimmune diseases.
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Dazhi Xu, PHD, MD (+86) 020-87343737 xudzh@sysucc.org.cn

Locations
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China
Anqing Municipal Hospital Recruiting
Anqing, China
Contact: Yaming Zhang, MD         
Second Affiliated Hospital, School of Medicine Recruiting
Hangzhou, China
Contact: Li Chen, MD         
Anhui Provincial Hospital Recruiting
Hefei, China
Contact: Xuhui Zhao, MD         
Jiangxi Provincial Cancer Hospital Recruiting
Nanchang, China
Contact: Huamin Rao, MD         
Dazhi Xu Recruiting
Shanghai, China
Contact: Dazhi Xu, PHD,MD       xudzh@sysucc.org.cn   
First Affiliated Hospital of Wannan Medical College Recruiting
Wuhu, China
Contact: Lianghui Shi, MD         
Sponsors and Collaborators
Fudan University
Investigators
Layout table for investigator information
Principal Investigator: Dazhi Xu, PHD, MD Fudan University
Tracking Information
First Submitted Date  ICMJE May 6, 2019
First Posted Date  ICMJE May 8, 2019
Last Update Posted Date May 31, 2019
Actual Study Start Date  ICMJE January 1, 2019
Estimated Primary Completion Date January 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 6, 2019)
DFS [ Time Frame: 3-year ]
Disease-free survival
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2019)
OS [ Time Frame: 5-year ]
Overall survival
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: May 6, 2019)
Side effects [ Time Frame: 1-year ]
Complications such as Nausea, vomiting, myelosuppression, and Liver or kidney function disorder
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE S-1 for 9 Months Versus 1 Year for Stage II Gastric Cancer (SMAC)
Official Title  ICMJE Compare S-1 for 9 Months to 1 Year as Adjuvant Chemotherapy in Stage II Gastric Cancer (SMAC)
Brief Summary

The study aims to compare the efficacy and safety of S-1 for 9 months versus S-1 for 1 year as adjuvant chemotherapy after D2 resection in patients with gastric cancer.

Hypothesis: For gastric patients after D2 resection, S-1 for 9 months shows non-inferiority to S-1 for 1 year in disease-free survival(DFS), overall survival (OS) and safety.

Detailed Description

It has been identified that S-1 is an effective adjuvant treatment for East Asian patients who have undergone a D2 dissection for locally advanced gastric cancer(GC) in the Japanese Adjuvant Chemotherapy Trial of TS-1(S-1) for Gastric Cancer (ACTS-GC) trail, And S-1 has become one of the standard therapies to these patients. But it is still unknown whether it would improve equally or even more to overall survival(OS) and disease-free survival(DFS) than S-1 for 1 year compared with S-1 for 9 months. As a result, An further clinical trial is still needed, This trial is designed to investigate the efficacy and safety of S-1 for 9 months versus S-1 for 1 year as adjuvant chemotherapy after D2 resection in patients with gastric cancer.

In this study, patients histologically confirmed stage II and who received D2 resection were randomly assigned to receive S-1 for 9 months or S-1 for 1 year. Patients aged from 18 to 75 years and adequate organ function are randomized 1:1 to S-1 for 9 months and S-1 for 1 year. Both are the 3-week recycle of S-1 (80-120mg per day) for 2 weeks, followed by 1 week of rest. The primary endpoint is 3-year DFS, and the secondary endpoint is 5-year OS and safety. Final study analysis will be conducted at the end of the 5th year after the last patient's enrollment. In summary, we hold the hypothesis that S-1 for 9 months is equally effective, safer, and easier to carry out. If possible, there will be a new adjuvant chemotherapy strategy for gastric cancer patients after D2 resection.

To ensure the quality of the study, two interim analyses will be planned at the half and the completion of the study respectively. The DATA and Safety Monitoring Committee will independently review the interim analysis and stop the study ahead of schedule if necessary. Furthermore, to improve the study progress and quality, the in-house interim monitoring will be performed.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Gastric Cancer
Intervention  ICMJE
  • Drug: S-1 for 9 months
    S-1 for 9 months after D2 resection
    Other Name: Tegafur,Gimeracil and Oteracil Porassium Capsules
  • Drug: S-1 for 1 year
    S-1 for 1 year after D2 resection
    Other Name: Tegafur,Gimeracil and Oteracil Porassium Capsules
Study Arms  ICMJE
  • Experimental: S-1 for 9 months
    S-1 80-120mg daily for 14 days in 3 weeks for totally 9 months after D2 resection
    Intervention: Drug: S-1 for 9 months
  • Active Comparator: S-1 for 1 year
    S-1 80-120mg daily for 14 days in 3 weeks for totally 1 year after D2 resection
    Intervention: Drug: S-1 for 1 year
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 6, 2019)
1006
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 1, 2027
Estimated Primary Completion Date January 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. The lower age limit of research subjects 18 years old and upper age limit of 75 years old.
  2. Be proven to be primary adenocarcinoma of gastric cancer and staged II by pathological evidence
  3. R0 surgery with lymphadenectomy
  4. Without any other malignancies
  5. ECOG (ECOG score standard) performance status of 0 or 1 and expected to survive more than 6 months
  6. No contraindications to chemotherapy, including normal peripheral blood routine, liver, and kidney function and electrocardiogram (WBC≥4.0 x 109 /L, NEU≥1.5 x 109 /L, PLT≥100 x 109 /L and HGB≥90g/L).

Exclusion Criteria:

  1. Female in pregnancy or lactation, or refuse to receive Contraception measures during chemotherapy.
  2. Patients with stage I, III and IV.
  3. Unavailable for R0 resection and D2 lymph node dissection.
  4. Suffering from other uncontrolled diseases, such as other tumors, acute and Chronic infection.
  5. With severe heart disease, including congestive heart failure, uncontrolled arrhythmias, unstable angina, myocardial infarction, severe heart valve disease, and resistant hypertension.
  6. Any Known or suspected history of drug allergy test.
  7. The researchers believe the patient is not able to complete the entire course of the experiment.
  8. Patients (within 4 weeks) are receiving any other anti-cancer drugs therapy, biological therapy, radiation therapy, or Immunosuppressive therapy.
  9. Patients conform to any of the following: post-organ transplant, necessary for long-term immunosuppressive or suffering with autoimmune diseases.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Dazhi Xu, PHD, MD (+86) 020-87343737 xudzh@sysucc.org.cn
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03941561
Other Study ID Numbers  ICMJE CGCG006
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dazhi Xu, Fudan University
Study Sponsor  ICMJE Fudan University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Dazhi Xu, PHD, MD Fudan University
PRS Account Fudan University
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP