S-1+Oxaliplatin vs.S-1+Cisplatin First-line Treatment of Advanced or Recurrent Non-intestinal Type Gastric Adenocarcinoma Patients

A Randomized, Open, Multi-center, Phase III Study of S-1+Oxaliplatin vs.S-1+Cisplatin First-line Treatment in Advanced or Recurrent Non-intestinal Type Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma Patients

The purpose of this study is to evaluate the effectiveness and safety of S-1+Oxaliplatin vs.S-1+Cisplatin First-line Treatment in Advanced or Recurrent Non-intestinal Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma Patients.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: S-1; Drug: Cisplatin; Drug: Oxaliplatin

Detailed Description

The primary endpoint is Overall survival time (OS).Secondary endpoints are overall response rate (ORR), time to treatment failure (TTF),progression free survival (PFS)and the adverse reactions(AE) of the two groups .

Study design:

This is a prospective randomized control study.

Sample size:

Sample size considerations were based on the survival end point. The improvement in median survival from 10 months in the S-1+cisplatin arm to 13 months in the S-1+oxaliplatin arm was considered clinically relevant in this patient population. A total of 576 patients were required for a two-tailed log-rank test at the 5% significance and at least 80% power. The planned enrolled time was 48 months and 1 year of follow up, and a drop-out rate of 5%.

• Study Type: Interventional
• Enrollment (Actual): 576
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center

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:

1. histologically confirmed unresectable advanced or recurrent diffuse-type or mixed-type gastric adenocarcinoma or gastroesophageal junction adenocarcinoma.
2. 18 years old to 75 years old, able to conduct oral administration.
3. Measurable disease or non-measurable but evaluable disease, according to the Response Evaluation Criteria in Solid Tumours(RECIST 1.1)
4. No palliative chemotherapy and radiotherapy. Previous adjuvant or neoadjuvant chemotherapy , if applicable, more than 12 months.
5. ECOG systemic status score of 0 to 2.

6. normal organ function, that meet the following criteria:

   1. ALT and AST(≤2.5 times ULN (≤5 times ULN in patients with liver metastases)
   2. ALP ≤ 2 times ULN ; (for patients with liver metastases can be no limit to the ALP).
   3. Total bilirubin ≤ 1 times ULN.
   4. Absolute neutrophil count ≥ 2.0 × 10^9 / L.
   5. Platelet count ≥ 100 × 10^9 / L.
   6. Hemoglobin ≥ 80g / L.
   7. Creatinine ≤ 1.25 times ULN.
   8. The estimated creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula).
7. Signed informed consent, treatment, follow-up and inspection in accordance with the study protocol.
8. Life expectancy greater than 3 months.
9. At least 3 weeks after major surgery.

Exclusion Criteria:

1. Previous adjuvant or neoadjuvant chemotherapy within the prescribed time

2. the investigator determines that the patient is not suitable for participation in this study, and specifically includes (but is not limited to):

   1. The past five years there have been other malignancies, but after appropriate treatment of cervical carcinoma in situ and non-melanoma skin cancer.
   2. brain metastases or leptomeningeal metastasis.
   3. myocardial infarction (within the past six months), severe unstable angina, congestive heart failure.
   4. Serious complications (including paralytic ileus, intestinal obstruction, interstitial pneumonia, lung fibrosis, beyond the control of diabetes, renal insufficiency and cirrhosis of the liver, etc.).
   5. Chronic nausea, vomiting, or diarrhea (per day greater than or equal to 4 times or watery stools).
   6. Gastrointestinal bleeding, and need for frequent blood transfusions.
   7. human immunodeficiency virus (HIV) carrier or suffering from AIDS (AIDS).
   8. Suffering from a mental illness.
   9. neuropathy severity ≥grade 2 .
   10. Infectious disease or inflammation, body temperature ≥ 38 ℃.
3. Cisplatin, oxaliplatin, or S-1 allergy.
4. Pregnancy or breast-feeding women.
5. refused to take appropriate contraceptive measures (including male patients).
6. Under experimental drug within 4 weeks.
7. Under other anti-cancer treatment.
8. HER2 IHC(3+) or IHC(2+) /FISH(+)

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
Active Comparator: S-1 + cisplatin(SP); S-1：40~60mg bid，d1~14 q3W cisplatin：60mg/m2，iv drip ，d1,q3W Number of Cycles: until progression or unacceptable toxicity develops.	Drug: S-1; S-1：40~60mg bid，d1~14 q3W; Drug: Cisplatin; cisplatin：60mg/m2，iv drip ，d1,q3W
Experimental: S-1+Oxaliplatin（SOX）; S-1：40~60mg bid，d1~14 q3W oxaliplatin：130mg/m2，iv drip for 2h，d1,q3W Number of Cycles: until progression or unacceptable toxicity develops.	Drug: S-1; S-1：40~60mg bid，d1~14 q3W; Drug: Oxaliplatin; oxaliplatin：130mg/m2，iv drip for 2h，d1,q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	OS means that from the first dose of treatment drug to death or lost, the follow-up visit will be performed every 12 weeks till death or lost	1-1.5 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	The primary endpoint is objective response rate,which equals CR+PR.	1 year
time to treatment failure (TTF)	The duration is from the randomized time to treatment termination due to any reason. The reasons may include disease progression, treatment toxicity, patient selection or death.	6 months
progression-free survival (PFS)	The duration is from the randomized time to disease progression or death due to any reason.	6 months
Adverse events (AE)		1-1.5 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Taiho Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: ruihua xu, Professor, SunYat-Sen University Cancer Center

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: April 1, 2013
• First Submitted That Met QC Criteria: April 1, 2013
• First Posted (Estimate): April 4, 2013

Study Record Updates

• Last Update Posted (Actual): January 23, 2019
• Last Update Submitted That Met QC Criteria: January 18, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: safety; Advance Gastric Cancer; Gastroesophageal Junction Adenocarcinoma; ORR,; OS,; TTF,; PFS,; Non-intestinal type gastric cancer; Recurrent Gastric Cancer; SOX, S-1+Oxaliplatin
• 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; Cisplatin; Oxaliplatin
• Other Study ID Numbers: SOX-DGCA