Phase III Study to Compare Perioperative Chemotherapy of Oxaliplatin Combined With S-1(SOX) Versus SOX or Oxaliplatin With Capecitabine (XELOX) as Post-operative Chemotherapy in Locally Advanced Gastric Adenocarcinoma With D2 Dissection

Sponsor

Peking University (Other)

Overall Status

Unknown status

CT.gov ID

NCT01534546

Collaborator

Taiho Pharmaceutical Co., Ltd. (Industry)

1,094

Enrollment

Locations

Arms

114

Duration (Months)

547

Patients Per Site

4.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Peri-operative treatment of locally advanced gastric cancer (LAGC) has always been argued by eastern and western scholars. For patients with clinical stage of cT4b/N+M0, or cT4aN+M0, the prognosis is rather poor, and the primary lesions might not be resectable at the time of diagnosis. MAGIC study has showed that pre-and post-operative chemotherapy with 3 cycles of ECF has increased 13% on 5yOS compared with surgery alone; However, eastern studies such as ACTS GC or CLASSIC showed that TS-1 monotherapy or XELOX (oxaliplatin/capecitabine) combination given as adjuvant chemotherapy for stage II or III patients after D2 surgery could achieve the significant survival benefit. So whether perioperative or post operative therapy is more beneficial for LAGC patients lacks of data supported by prospective study.

So in this prospective randomized phase III study, the investigators aim to compare the survival benefit as well as the safety for SOX (oxaliplatin/TS-1) as perioperative therapy versus SOX or XELOX as postoperative therapy after D2 dissection.

Condition or Disease	Intervention/Treatment	Phase
Advanced Gastric Carcinoma	Drug: Oxaliplatin capecitabine Drug: Oxaliplatin S-1 Drug: Oxaliplatin S-1	Phase 3

Detailed Description

detailed discription of protocol updated on Feb 2013; detailed discription of protocol updated on Apr 2013; detailed discription of protocol updated on Oct 2013;

Study Design

Study Type:

Interventional

Actual Enrollment :

1094 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized, Multicenter, Controlled Phase III Study to Compare Perioperative Chemotherapy of Oxaliplatin Combined With S-1(SOX) Versus SOX or Oxaliplatin With Capecitabine (XELOX) as Post-operative Chemotherapy in Locally Advanced Gastric Adenocarcinoma With D2 Dissection

Study Start Date :

Mar 1, 2012

Actual Primary Completion Date :

Jul 1, 2019

Anticipated Study Completion Date :

Sep 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: arm A postoperative Oxaliplatin/capecitabine（XELOX） postoperative Oxaliplatin/capecitabine（XELOX） patients in arm A will receive standard gastrectomy with D2 Lymphadenectomy first, and 8 cycles of adjuvant XELOX later. capecitabine：1000 mg/m2 ，bid, d1~14 q3W oxaliplatin：130mg/m2，iv drip for 2h，d1,q3W 8 cycles (6 months)	Drug: Oxaliplatin capecitabine capecitabine：1000 mg/m2 ，bid, d1~14 oxaliplatin：130mg/m2，iv drip for 2h，d1
Experimental: arm B: postoperative Oxaliplatin/S-1（SOX） postoperative Oxaliplatin/S-1（SOX） patients in arm B will receive standard gastrectomy with D2 Lymphadenectomy first, and 8 cycles of adjuvant SOX later. S-1：40~60mg bid，d1~14 q3W oxaliplatin：130mg/m2，iv drip for 2h，d1,q3W 8 cycles (6 months)	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
Experimental: Arm C：postoperative Oxaliplatin /S-1（SOX） Postoperative Oxaliplatin /S-1（SOX） patients in arm C will receive 3 cycles of neoadjuvant SOX first, and then standard gastrectomy with D2 lymphadenectomy, and 5 cycles of adjuvant SOX followed by 3 cycles of S-1 monotherapy. Dose of s-1 and oxaliplatin are same to arm B Dose of S-1 monotherapy is same to combination therapy (SOX 3 cycles before surgery, 5 cycles of SOX and 3 cycles of S-1 monotherapy, 6 months after surgery)	Drug: Oxaliplatin S-1 S-1: 40~60mg bid，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 S-1 monotherapy as the same dose and schedule of the above

Arm

Intervention/Treatment

Active Comparator: arm A postoperative Oxaliplatin/capecitabine（XELOX）

postoperative Oxaliplatin/capecitabine（XELOX） patients in arm A will receive standard gastrectomy with D2 Lymphadenectomy first, and 8 cycles of adjuvant XELOX later. capecitabine：1000 mg/m2 ，bid, d1~14 q3W oxaliplatin：130mg/m2，iv drip for 2h，d1,q3W 8 cycles (6 months)

Drug: Oxaliplatin capecitabine

capecitabine：1000 mg/m2 ，bid, d1~14 oxaliplatin：130mg/m2，iv drip for 2h，d1

Experimental: arm B: postoperative Oxaliplatin/S-1（SOX）

postoperative Oxaliplatin/S-1（SOX） patients in arm B will receive standard gastrectomy with D2 Lymphadenectomy first, and 8 cycles of adjuvant SOX later. S-1：40~60mg bid，d1~14 q3W oxaliplatin：130mg/m2，iv drip for 2h，d1,q3W 8 cycles (6 months)

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

Experimental: Arm C：postoperative Oxaliplatin /S-1（SOX）

Postoperative Oxaliplatin /S-1（SOX） patients in arm C will receive 3 cycles of neoadjuvant SOX first, and then standard gastrectomy with D2 lymphadenectomy, and 5 cycles of adjuvant SOX followed by 3 cycles of S-1 monotherapy. Dose of s-1 and oxaliplatin are same to arm B Dose of S-1 monotherapy is same to combination therapy (SOX 3 cycles before surgery, 5 cycles of SOX and 3 cycles of S-1 monotherapy, 6 months after surgery)

Drug: Oxaliplatin S-1

S-1: 40~60mg bid，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 S-1 monotherapy as the same dose and schedule of the above

Outcome Measures

Primary Outcome Measures

3 year Disease Free Survival [3 years]
perioperative chemotherapy of SOX is superior than postoperative SOX after D2 dissection in LAGC. Postoperative SOX is non inferior to XELOX.

Secondary Outcome Measures

5 year Overall Survival [5 years]
perioperative chemotherapy of SOX is superior than postoperative SOX after D2 dissection in LAGC. Postoperative SOX is non inferior to XELOX.
Adverse Event [1year]
peri-operation morbidity, mortality, and other adverse events including chemotherapy related ones.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

sign written informed consent form
age ≥ 18 years
pathologically confirmed gastric or GEJ adenocarcinoma
disease at clinical stage of resectable or potentially resectable LAGC（T4a-b/N+M0）
No prior antitumor treatment is allowed, including chemotherapy, radiotherapy, immune therapy or target therapy
Adequate organ function as defined below:

Hematologic ANC ≥ 1.5109/l Hemoglobin ≥ 9 g/dl Platelets ≥ 100109/l Hepatic Albumin ≥ 30g/l Serum bilirubin ≤ 1.5×ULN AST and ALT ≤ 2.5×ULN ALP ≤ 2.5×ULN TBIL ≤ 1.5×ULN Renal Serum Creatinine < 1.5 ULN

KPS ≥ 70
Adequate lung and heart function
Negative serum or urine pregnant test within 7 days prior to randomization for child-bearing age women
Sexually active males or females willing to practice contraception during the study until 30 days after end of study.

Exclusion Criteria:

Refuse to provide blood/tissue sample；
With distant metastasis；
Sexually active males or females refuse to practice contraception during the study until 30 days after end of study.
Known hypersensitivity reaction or metabolic disorder to fluorpyrimidines or oxaliplatin；
≥ grade 1 peripheral neuropathy；
History of organ transplantation（including autologous bone marrow transplantation and Peripheral stem cell transplantation）；
Prior long term steroid therapy (excluding short term steroid treatment which is completed prior to > 2 weeks of study enrollment)；
Patients with central nervous system(CNS) disorder or peripheral nervous system disorder or psychiatric disease；
Concurrent severe infection；
unable to swallow; (complete or incomplete)gastrointestinal obstruction; gastrointestinal bleeding; gastrointestinal perforation；
Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety (including current active hepatic, biliary, renal, respiratory disease, uncontrolled diabetes hypertension et al)；
History of other malignancy. However, subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma, are eligible；
Known history of uncontrolled or symptomatic angina, uncontrolled arrhythmias and hypertension, or congestive heart failure, or cardiac infarction within 6 months prior to study enrollment, or cardiac insufficiency；
Person with no capacity (legally) or inappropriate to continue study treatment for ethics/medical reasons；