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

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

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.

Study Overview

• Status: Unknown
• Conditions: Gastric Adenocarcinoma
• Intervention / Treatment: Drug: Oxaliplatin+S-1; Drug: Adjuvant Oxaliplatin/S-1（SOX）

• Study Type: Interventional
• Enrollment (Anticipated): 772
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Tao Li, MD,PhD; Phone Number: 86-10-66938328; Email: litbj301@sina.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100853
      • Recruiting
      • Chinese PLA General Hospital
      • Contact: Tao Li, MD,PhD; Phone Number: 0086-10-66938328; Email: litbj301@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically confirmed gastric adenocarcinoma
2. Gastroesophageal junction tumour type II or III(NCCN 2009) can be enrolled
3. 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
4. planning to undergo gastric cancer D2 surgery after neoadjuvant chemotherapy
5. KPS > 60; ECOG performance status 0-2
6. Life expectancy > 6 months
7. Age: 20 to 75 years
8. No other severe disease and life expectancy less than five years

9. 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
10. Disease had to be measurable by the Response Evaluation Criteria in Solid Tumors (RECIST1.1) criteria
11. Written informed consent and able to comply with the protocol

Exclusion Criteria:

1. Patient cannot undergo surgery or chemotherapy because of other severe disease
2. Be allergic to chemotherapy drugs
3. Patients receiving any chemotherapy or drugs involved in this trial in four weeks before enrolled
4. Patients received cytotoxic chemotherapy, targeted therapy, immunotherapy or radiotherapy for gastric cancer
5. Within the last 5 years in patients with a history of other malignant diseases
6. Pregnant or breast-feeding women
7. 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
8. Patients with upper gastrointestinal obstruction or absorption anomaly; patient in obstruction of the Helicobacter pylori failure like effect S-1 to take and absorb
9. Patients with a history of peripheral nerve disease
10. Patients who get organ transplant
11. lack of dihydropyrimidine dehydrogenase (DPD)
12. Infection or other disease failure to control

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: 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
disease free survival	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.	three years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
response rate	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.	3 months
overall survival	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.	five years
safety	Number of participants with adverse events related to SOX chemotherapy.All adverse events are from CTCAE 4.0 criteria.	six months

Collaborators and Investigators

• Sponsor: Lin Chen

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Anticipated): September 1, 2014
• Study Completion (Anticipated): January 1, 2017

Study Registration Dates

• First Submitted: April 4, 2012
• First Submitted That Met QC Criteria: April 23, 2012
• First Posted (Estimate): April 24, 2012

Study Record Updates

• Last Update Posted (Estimate): April 24, 2012
• Last Update Submitted That Met QC Criteria: April 23, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: disease free survival; D2 lymphadenectomy; two arms; chemotherapy before and after surgery
• 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: LCHEN-PLAGH