Oxaliplatin plus S-1 or capecitabine chemotherapy before or after surgery for locally advanced gastric cancer with D2 lymphadenectomy: a phase II-III randomized trial
| ISRCTN | ISRCTN12206108 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12206108 |
| Secondary identifying numbers | D171100006517002 |
- Submission date
- 28/02/2018
- Registration date
- 07/03/2018
- Last edited
- 05/12/2018
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
Gastric cancer is a common cancer worldwide. Surgery is the primary treatment but alone fails to produce satisfactory treatment outcomes. Therefore, chemotherapy (drug treatment) administered after surgery has been used along with surgery to improve patient survival. Recently, preoperative chemotherapy was proposed and has been applied as an alternative to postoperative chemotherapy. Compared with postoperative chemotherapy, preoperative chemotherapy might show patient benefit in terms of fewer adverse effects and higher tolerance of the regimens. However, it is not known whether preoperative chemotherapy is better than postoperative chemotherapy in preventing death. The current study therefore aims to compare pre- and post-operative chemotherapy using oxaliplatin plus S-1 (SOX) or oxaliplatin plus capecitabine (CapeOX) on gastric cancer patients receiving gastrectomy (stomach surgery to remove cancer) with D2 lymphadenectomy (removal of lymph nodes around the stomach).
Who can participate?
Adult patient with gastric cancer.
What does the study involve?
Participants are randomly allocated to one of four groups. Those in the first group receive 2 cycles of SOX before the surgery and 6 cycles after the surgery. Those in the second group receive 2 cycles of CapeOX before the surgery and 6 cycles after the surgery. Those in the third group receive 8 cycles of SOX after the surgery. Those in the last group receive 8 cycles of CapeOX after the surgery. Participants are assessed for adverse effect of chemotherapy and survival status during the study.
What are the possible benefits and risks of participating?
Participants can benefit from improvements in their diseases. Those receiving preoperative chemotherapy may benefit from fewer adverse effects and better tolerance to the regimens. Those receiving postoperative chemotherapy may benefit from early performance of surgery. There are small risks of surgical complications, adverse effects of chemotherapy, and discomfort and bleeding when providing blood samples.
Where is the study run from?
Peking University Cancer Hospital (Beijing, China)
When is the study starting and how long is it expected to run for?
September 2011 to December 2017
Who is funding the study?
This trial was supported in part by grants from Beijing Municipal Science & Technology Commission (D171100006517002).
Who is the main contact?
Dr. Xue Kan (Scientific)
xuekan213@163.com
Contact information
Scientific
No.52 Fucheng Rd., Haidian District, Beijing
Beijing
100142
China
Study information
| Study design | Single-center open-label randomized controlled phase II/III trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet. |
| Scientific title | Efficacy and safety of oxaliplatin plus S-1 or capecitabine as neoadjuvant or adjuvant chemotherapy for locally advanced gastric cancer with D2 lymphadenectomy: a phase II-III randomized trial |
| Study objectives | Neoadjuvant chemotherapy is superior to adjuvant chemotherapy using SOX or CapeOX as the regimen. |
| Ethics approval(s) | Peking University Cancer Hospital Ethical Committee, approval September 2011, approval document issued 2012, 2012101606. |
| Health condition(s) or problem(s) studied | Locally advanced gastric cancer |
| Intervention | Eligible patients were randomly assigned to one of the four arms: neoadjuvant SOX (peri-SOX), neoadjuvant CapeOX (peri-CapeOX), adjuvant SOX (post-SOX), and adjuvant CapeOX (post-CapeOX). Patients receiving neoadjuvant chemotherapy started chemotherapy within 3 days after the laparoscopic exploration; and after 2 cycles of chemotherapy, the clinical stage of the tumor was evaluated before the surgery was performed. Radical dissection was aimed in gastrectomy, with standard D2 lymphadenectomy. Patients receiving adjuvant chemotherapy had surgery immediately after the randomization. After the surgery, patients in neoadjuvant chemotherapy arms received 6 cycles of postoperative chemotherapy, whereas 8 cycles were administered to the adjuvant arms. Patients randomized to SOX regimens received oral S-1 (80 mg/m2 twice daily on day 1-14) and intravenous oxaliplatin (130 mg/m2 on day 1) for each cycle, whereas the CapeOX patients received oral capecitabine (1000 mg/m2 twice daily on day 1-14) and intravenous oxaliplatin (130 mg/m2 on day 1). Dose reduction and interruptions were allowed for potentially serious and life-threatening adverse events that were determined by clinicians. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II/III |
| Drug / device / biological / vaccine name(s) | S1 (tegafur + gimeracil + oteracil), oxaliplatin, capecitabine |
| Primary outcome measure | Overall survival (time interval from the time of randomization to the date of all-cause death or last follow-up). Follow-up was conducted by phone call every 6 months after completion or termination of treatment. |
| Secondary outcome measures | The secondary endpoints included treatment completion rate, surgical complications, chemotherapy adverse events and pathological complete response rate. Treatment completion rate was recorded when the treatment was completed or stopped. Surgical complications were measured during and after surgery. Complete response rate was reported by pathologists after the surgery. Pathological stage was evaluated according to the 7th edition of the American Joint Committee on Cancer TNM Staging Classification for Carcinoma of the Stomach. The clinical response was evaluated by the Response Evaluation Criteria for Solid Tumors (RECIST) in computed tomography and by the downstaging assessed by endoscopic ultrasound using Choi criteria by the end of the second cycle of neoadjuvant chemotherapy (NACT). Pathology response to NACT was evaluated according to the 3rd English edition of the Japanese Classification of Gastric Cancer. |
| Overall study start date | 01/03/2011 |
| Completion date | 31/12/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 224 |
| Key inclusion criteria | 1. Aged between 18 and 80 years 2. Pathologically confirmed gastric adenocarcinoma 3. Disease at the clinical stage of resectable advanced gastric cancer (T2-4NanyM0), without peritoneal metastasis as confirmed by laparoscopy and cytological pathology 4. Eastern Cooperative Oncology Group performance status of 0 or 1 5. No previous treatment history 6. Adequate organ function levels (hematological ANC ≥1.5x10(9)/l, hemoglobin ≥9 g/dl, platelets ≥ 100x10(9)/l, hepatic albumin ≥30 g/l, serum bilirubin ≤1.5x the upper limit of normal [ULN], AST and ALT ≤2.5×ULN, ALP ≤2.5×ULN, TBIL ≤1.5×ULN, renal serum creatinine <1.5xULN) 7. Adequate lung and heart function, without ECG-confirmed ischemic change or ventricular arrhythmias |
| Key exclusion criteria | 1. Serious comorbidities 2. Distant metastasis 3. Acute inflammation 4. Systematic steroid therapy 5. Pregnant or breast-feeding women or women considering pregnancy 6. Nervous system disorder or psychiatric disease 7. Medical history of allergy or hypersensitivity to any drugs 8. Patient refusal |
| Date of first enrolment | 01/09/2011 |
| Date of final enrolment | 31/12/2012 |
Locations
Countries of recruitment
- China
Study participating centre
China
Sponsor information
University/education
No.52 Fucheng Rd., Haidian District, Beijing
Beijing
100042
China
"ROR" |
https://ror.org/00nyxxr91 |
|---|
Funders
Funder type
Not defined
No information available
Results and Publications
| Intention to publish date | 30/06/2018 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal 6 months after the overall trial end. |
| IPD sharing plan | The data in the current study can be shared on journal editor's request. Please contact Dr. Xue Kan on xuekan213@163.com for details of data sharing. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/10/2018 | Yes | No |
Editorial Notes
05/12/2018: Publication reference added.
