Stomach Neoplasm
Conditions
Keywords
Stomach Neoplasms, Cytoreduction Surgical Procedures
Brief summary
This study evaluates the survival benefit and safety of cytoreductive surgery(CRS) combined with HIPEC and chemotherapy in gastric cancer with peritoneal metastasis.
Detailed description
Peritoneal metastasis is one of the most frequent non-curable factors in advanced gastric cancer with poor prognosis, the median survival time of patients is less than 1 year and even worse in China. Recently, several new modalities have been developed and reported to improve survival, including the new chemotherapeutic agents, molecular targeting agents and hyperthermic intraperitoneal chemotherapy（HIPEC）.Still, the long-term outcomes based on multicenter randomized clinical trials (RCTs) are awaited. The surgical approach to metastatic lesions has been proved to play a very crucial role in prolonging the survival of metastatic colorectal patients, which might be able to cure patients with the operation aiming at R0 resection. For patients with metastatic gastric cancer, surgical intervention of primary tumor and measurable metastatic lesion is technically feasible, while the survival benefit is controversial. Even though the REGATTA trial demonstrated that the removal of the primary tumor is not necessarily beneficial, the role of operation aiming at R0 resection combined with new regimens like HIPEC and new chemotherapeutic agents is still confusing and new categories of classification for metastatic gastric cancer based on the treatment response is needed. In order to evaluate the survival benefit and safety of cytoreductive surgery(CRS) and HIPEC before beginning chemotherapy in gastric cancer with peritoneal metastasis, patients who fulfill the inclusion and exclusion criteria will be recruited in this study and receive CRS, HIPEC and chemotherapy. Chemotherapy regimen based on cisplatin and fluorouracil(CF) are recommended. Patients are followed up for 2 years and the safety and survival outcome will be analyzed.
Interventions
PROCEDURECytoreductive surgery
Gastrectomy with D2 lymph node dissection and Metastasectomy for peritoneal metastatic sites only. A total, distal, or proximal gastrectomy and the type of reconstruction will be selected according to the surgeon's experience. Metastasectomy is limited to peritoneal metastatic sites only to render the patient no evidence of disease (NED) with at least 1cm negative margins when possible.
PROCEDUREHyperthermic Intraperitoneal Chemotherapy
Docetaxel 120 mg diluted in 5.0 L of saline is forced into the abdomen through the inflow catheter by a pump and pulled out through the drains as a heated intraperitoneal perfusion.A heat exchanger keeps the intraperitoneal fluid at 43±0.5℃ and duration limited to 70 minutes.24 hours after cytoreductive surgery no less than 2 cycles postoperative chemotherapy will be recommended.
DRUGFluoropyrimidine
CF regimens or other first line regimens based on Fluoropyrimidine and Platinum according to the NCCN Guidelines（Gastric Cancer，version 3.2016) are recommended.Regimens and dosing schedules are not limited in this trial.
DRUGCisplatin
CF regimens or other first line regimens based on Fluoropyrimidine and Platinum according to the NCCN Guidelines（Gastric Cancer，version 3.2016) are recommended.Regimens and dosing schedules are not limited in this trial.
Sponsors
Nanfang Hospital, Southern Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Age from over 18 to under 75 years * Histologically proven primary gastric adenocarcinoma confirmed pathologically by endoscopic biopsy * Diagnosed with clinical T1-4N0-3M1（distant metastases confined to peritoneum, P1）according to the American Joint Committee on Cancer(AJCC) Cancer Staging Manual Seventh Edition by laparoscopic exploration * Localized peritoneal metastasis with peritoneal cancer index(PCI) less than 20 * Resection of primary tumor and metastasis is anticipated to reach the CC0 status(no residual tumor ) * Performance status of 0 or 1 on Eastern Cooperative Oncology Group(ECOG) scale * Written informed consent
Exclusion criteria
* Adenocarcinoma of esophageal-gastric junction(AEG) that requires thoracotomy * Distant metastases not confined to peritoneum, including liver (H1), para-aortic lymphnode (stations 16a1 and/or b2), lung, brain, bone and other organs * Histologically proven Human epidermal growth factor receptor 2(HER2)-neu overexpressing adenocarcinoma * History of previous neoadjuvant chemotherapy , radiotherapy or clinical trial treatment within 3 months * Contraindication for anesthesia, surgery, chemotherapeutic agents or HIPEC * Women of child-bearing potential who are pregnant or breastfeeding * History of prior/other malignancies within the 5 years prior to enrollment * Cerebrovascular accident occurred within 6 months (myocardial infarction, unstable angina, cerebral infarction, or cerebral hemorrhage) * History of continuous systematic administration of corticosteroids within one month * Requirement of simultaneous surgery for other disease * Emergency surgery due to complication (bleeding, obstruction or perforation) caused by gastric cancer * FEV1\<50% of predicted values
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2-year Median survival time | 24 months | The time point when the cumulative survival rate is 50% according to the survival curve. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 2-year overall survival rate | 24 months | Overall survival rate calculated according to the survival curve. |
| Progression free survival rate | 24 months | Progression free survival rate calculated according to the disease progression curve. |
| Morbidity and mortality | 30 days; 24 months | The early complication and mortality are defined as the event observed within 30 days after intervention, while the time frame for late complication is the period beyond 30 days after intervention to the end of month 24th. Complications are ranked from grade 0-5 according to CTCAE V4.0 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Quality of life(site-specific module for gastric cancer) | Every 6 months to 2 years | Evaluated according to European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Stomach(EORTC QLQ-STO22) |
| Molecular biomarker alteration | Every 6 months to 2 years | Molecular biomarker includes 14 genes（TP53, BAI1, THSD1, ARID2, KIAA2022, ERBB4, ZNF721, NT5E, PDE10A, CA1, NUMB, NBN, ZFYVE16 and NCAM1） according to the whole-exome sequencing results. |
| Quality of life | Every 6 months to 2 years | Evaluated according to European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Cancer (EORTC QLQ-C30) |
| circulating tumor cell（CTC） alteration | Every 6 months to 2 years | — |
| circulating tumor DNA（ctDNA）alteration | Every 3 months to 2 years | — |
Countries
China
Contacts
Primary ContactGuoxin Li, M.D., Ph.D.
Backup ContactHao Liu, M.D., Ph.D.
Outcome results
None listed