RESONANCE: SOX Regimen as Neoadjuvant Chemotherapy for AJCC Stage II-III Gastric Cancer

Sponsor

Lin Chen (Other)

Overall Status

Unknown status

CT.gov ID

NCT01583361

Collaborator

(none)

772

Enrollment

Location

Arms

58.1

Duration (Months)

13.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized, multicenter, controlled trial to prove efficacy of S-1 and Oxaliplatin as Neoadjuvant Chemotherapy for Advanced Gastric Cancer Patients who undergo D2 gastrectomy.

The primary endpoint is three-year free disease and the second primary includes five-year overall survival, safety and R0 resection rate.

Condition or Disease	Intervention/Treatment	Phase
Gastric Adenocarcinoma	Drug: Oxaliplatin+S-1 Drug: Adjuvant Oxaliplatin/S-1（SOX）	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

772 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase III, Randomized, Multicenter, Controlled Evaluation of S-1 and Oxaliplatin as Neoadjuvant Chemotherapy for Advanced Gastric Cancer Patients

Study Start Date :

Mar 1, 2012

Anticipated Primary Completion Date :

Sep 1, 2014

Anticipated Study Completion Date :

Jan 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A:Neoadjuvant sox Patients in arm a will receive (N=2-4) cycles of neoadjuvant SOX first, and then standard gastrectomy with D2 lymphadenectomy, and (8-N) cycles of adjuvant SOX adjuvant chemotherapy.	Drug: Oxaliplatin+S-1 S-1: 40~60mg bid，po, d1~14 （S-1：BSA <1.25m2, 40mg bid, 1.25m2≤BSA≤1.5m2,50mg bid, BSA>1.5m2, 60mg bid） oxaliplatin：130mg/m2，iv drip for 2h，d1 Other Names: Oxaliplatin(Sanofi-aventis) S-1(Taiho)
Active Comparator: Arm B:Adjuvant SOX Patients in arm B will receive standard gastrectomy with D2 Lymphadenectomy first, and 8 cycles of adjuvant SOX later.	Drug: Adjuvant Oxaliplatin/S-1（SOX） S-1：40~60mg bid，d1~14 q3W oxaliplatin：130mg/m2，iv drip for 2h，d1,q3W 8 cycles (6 months) Other Names: Oxaliplatin(Sanofi-aventis) S-1(Taiho)

Arm

Intervention/Treatment

Experimental: Arm A:Neoadjuvant sox

Patients in arm a will receive (N=2-4) cycles of neoadjuvant SOX first, and then standard gastrectomy with D2 lymphadenectomy, and (8-N) cycles of adjuvant SOX adjuvant chemotherapy.

Drug: Oxaliplatin+S-1

S-1: 40~60mg bid，po, d1~14 （S-1：BSA <1.25m2, 40mg bid, 1.25m2≤BSA≤1.5m2,50mg bid, BSA>1.5m2, 60mg bid） oxaliplatin：130mg/m2，iv drip for 2h，d1

Other Names:

Oxaliplatin(Sanofi-aventis)

S-1(Taiho)

Active Comparator: Arm B:Adjuvant SOX

Patients in arm B will receive standard gastrectomy with D2 Lymphadenectomy first, and 8 cycles of adjuvant SOX later.

Drug: Adjuvant Oxaliplatin/S-1（SOX）

S-1：40~60mg bid，d1~14 q3W oxaliplatin：130mg/m2，iv drip for 2h，d1,q3W 8 cycles (6 months)

Other Names:

Oxaliplatin(Sanofi-aventis)

S-1(Taiho)

Outcome Measures

Primary Outcome Measures

disease free survival [three years]
SOX regimen as Neoadjuvant chemotherapy for AJCC II-III gastric cancer patients is superior than postoperative SOX after D2 surgery.Disease free survival is defined as time of surgery to recurrence or death.

Secondary Outcome Measures

response rate [3 months]
For neoadjuvant chemotherapy patients,response rate will be evaluated according to RECIST 1.1 criteria after at least 2 cycles of SOX chemotherapy.CT scan is required to every patient.
overall survival [five years]
Neoadjuvant chemotherapy of SOX is superior than postoperative SOX after D2 dissection in AJCC II-III gastric cancer patients.Overall survival is defined as the time of randomization to death.
safety [six months]
Number of participants with adverse events related to SOX chemotherapy.All adverse events are from CTCAE 4.0 criteria.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed gastric adenocarcinoma
Gastroesophageal junction tumour type II or III(NCCN 2009) can be enrolled
All patients must undergo EUS,CT(or PET-CT) and laparoscopy to evaluate tumor stage classification (TNM), and only stage II or III (AJCC 7th) gastric cancer patients can be enrolled
planning to undergo gastric cancer D2 surgery after neoadjuvant chemotherapy
KPS > 60; ECOG performance status 0-2
Life expectancy > 6 months
Age: 20 to 75 years
No other severe disease and life expectancy less than five years
7 days before enrolled, baseline data should be finished including:

Granulocyte count ≥ 1.5×109/L;
platelet count ≥ 100×109/L;
Hemoglobin ≥ 90g/L;
hepatic < 1.5×ULN;
total bilirubin ≤ 1.0×ULN;
creatinine < 1.5×ULN;
PT-INR/PTT < 1.7× ULN

Disease had to be measurable by the Response Evaluation Criteria in Solid Tumors (RECIST1.1) criteria
Written informed consent and able to comply with the protocol

Exclusion Criteria:

Patient cannot undergo surgery or chemotherapy because of other severe disease
Be allergic to chemotherapy drugs
Patients receiving any chemotherapy or drugs involved in this trial in four weeks before enrolled
Patients received cytotoxic chemotherapy, targeted therapy, immunotherapy or radiotherapy for gastric cancer
Within the last 5 years in patients with a history of other malignant diseases
Pregnant or breast-feeding women
Severe heart disease like symptoms of coronary heart disease, New York Heart Association (NYHA) grade II or worse congestive heart failure or cardiac arrhythmia having medications or myocardial infarction within the last 12 months
Patients with upper gastrointestinal obstruction or absorption anomaly; patient in obstruction of the Helicobacter pylori failure like effect S-1 to take and absorb
Patients with a history of peripheral nerve disease
Patients who get organ transplant
lack of dihydropyrimidine dehydrogenase (DPD)
Infection or other disease failure to control