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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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by Peking University
Sponsor:
Collaborator:
Taiho Pharmaceutical Co., Ltd.
Information provided by (Responsible Party):
Shen Lin, Peking University
ClinicalTrials.gov Identifier:
NCT01534546
First received: February 13, 2012
Last updated: April 15, 2013
Last verified: April 2013
  Purpose

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 Intervention Phase
Advanced Gastric Carcinoma
Drug: Oxaliplatin capecitabine
Drug: Oxaliplatin S-1
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Peking University:

Primary Outcome Measures:
  • 3 year Disease Free Survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    1. perioperative chemotherapy of SOX is superior than postoperative SOX after D2 dissection in LAGC.
    2. Postoperative SOX is non inferior to XELOX.


Secondary Outcome Measures:
  • 5 year Overall Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    1. perioperative chemotherapy of SOX is superior than postoperative SOX after D2 dissection in LAGC.
    2. Postoperative SOX is non inferior to XELOX.

  • safety [ Time Frame: 1year ] [ Designated as safety issue: Yes ]
    peri-operation morbidity, mortality, and other adverse events including chemotherapy related ones.


Estimated Enrollment: 1059
Study Start Date: March 2012
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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;
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01534546

Contacts
Contact: zhang xiaotian, MD 86-10-88196561 zhangxtxx@gmail.com
Contact: li ziyu, MD 86-10-88196050 ligregory369@hotmail.com

Locations
China
Lin Shen Not yet recruiting
Beijing, China
Contact: zhang xiaotian, MD    86-10-88196561    zhangxtxx@gmail.com   
Principal Investigator: ji jiafu, MD         
Principal Investigator: shen lin, MD         
Peking Unicersity Cancer Hospital Recruiting
Beijing, China
Contact: xiaotian zhang, MD         
Sponsors and Collaborators
Peking University
Taiho Pharmaceutical Co., Ltd.
  More Information

No publications provided

Responsible Party: Shen Lin, head of Department of gastrointestinal oncology, Peking University
ClinicalTrials.gov Identifier: NCT01534546     History of Changes
Other Study ID Numbers: CGOG1003-RESOLVE, CGOG 1003
Study First Received: February 13, 2012
Last Updated: April 15, 2013
Health Authority: China: Food and Drug Administration

Keywords provided by Peking University:
neoadjuvant chemotherapy
adjuvant chemotherapy
DFS
OS
safety
resectable locally advanced gastric carcinoma
potentially resectable locally advanced gastric carcinoma

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Stomach Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Stomach Diseases
Capecitabine
Fluorouracil
Oxaliplatin
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014