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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

Primary Purpose

Advanced Gastric Carcinoma

Status

Unknown status

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

Oxaliplatin capecitabine

Oxaliplatin S-1

About this trial

This is an interventional treatment trial for Advanced Gastric Carcinoma focused on measuring neoadjuvant chemotherapy, adjuvant chemotherapy, DFS, OS, safety, resectable locally advanced gastric carcinoma, potentially resectable locally advanced gastric carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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 ≥ 1.5*109/l Hemoglobin ≥ 9 g/dl Platelets ≥ 100*109/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；

Sites / Locations

Lin Shen
Peking Unicersity Cancer Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Arm Label

arm A postoperative Oxaliplatin/capecitabine（XELOX）

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

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

Arm Description

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)

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)

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)

Outcomes

Primary Outcome Measures

3 year Disease Free Survival

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

perioperative chemotherapy of SOX is superior than postoperative SOX after D2 dissection in LAGC. Postoperative SOX is non inferior to XELOX.

Adverse Event

peri-operation morbidity, mortality, and other adverse events including chemotherapy related ones.

Full Information

NCT ID

NCT01534546

First Posted

February 13, 2012

Last Updated

September 14, 2019

Sponsor

Peking University

Collaborators

Taiho Pharmaceutical Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT01534546

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Unknown status

Study Start Date

March 2012 (undefined)

Primary Completion Date

July 2019 (Actual)

Study Completion Date

September 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Peking University

Collaborators

Taiho Pharmaceutical Co., Ltd.

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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;

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Advanced Gastric Carcinoma

Keywords

neoadjuvant chemotherapy, adjuvant chemotherapy, DFS, OS, safety, resectable locally advanced gastric carcinoma, potentially resectable locally advanced gastric carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

1094 (Actual)

8. Arms, Groups, and Interventions

Arm Title

arm A postoperative Oxaliplatin/capecitabine（XELOX）

Arm Type

Active Comparator

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Oxaliplatin capecitabine

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Oxaliplatin S-1

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Oxaliplatin S-1

Intervention Description

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

Primary Outcome Measure Information:

Title

3 year Disease Free Survival

Description

perioperative chemotherapy of SOX is superior than postoperative SOX after D2 dissection in LAGC. Postoperative SOX is non inferior to XELOX.

Time Frame

3 years

Secondary Outcome Measure Information:

Title

5 year Overall Survival

Description

perioperative chemotherapy of SOX is superior than postoperative SOX after D2 dissection in LAGC. Postoperative SOX is non inferior to XELOX.

Time Frame

5 years

Title

Adverse Event

Description

peri-operation morbidity, mortality, and other adverse events including chemotherapy related ones.

Time Frame

1year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 ≥ 1.5*109/l Hemoglobin ≥ 9 g/dl Platelets ≥ 100*109/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；

Facility Information:

Facility Name

Lin Shen

City

Beijing

Country

China

Facility Name

Peking Unicersity Cancer Hospital

City

Beijing

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34252374

Citation

Zhang X, Liang H, Li Z, Xue Y, Wang Y, Zhou Z, Yu J, Bu Z, Chen L, Du Y, Wang X, Wu A, Li G, Su X, Xiao G, Cui M, Wu D, Chen L, Wu X, Zhou Y, Zhang L, Dang C, He Y, Zhang Z, Sun Y, Li Y, Chen H, Bai Y, Qi C, Yu P, Zhu G, Suo J, Jia B, Li L, Huang C, Li F, Ye Y, Xu H, Wang X, Yuan Y, E JY, Ying X, Yao C, Shen L, Ji J; RESOLVE study group. Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial. Lancet Oncol. 2021 Aug;22(8):1081-1092. doi: 10.1016/S1470-2045(21)00297-7. Epub 2021 Jul 9. Erratum In: Lancet Oncol. 2021 Aug;22(8):e347.

Results Reference

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