Background: Approximately 15% of gastric adenocarcinoma patients presents with peritoneal carcinomatosis (PC) at the first encounter and is regarded as an unresectable and end-stage disease. The recommended treatment with palliative chemotherapy alone yields a poor clinical efficacy. Emerging evidences suggest the survival benefits of complete cytoreductive surgery (CRS) combined with normothermic intraperitoneal chemotherapy (N-IPEC) for gastric adenocarcinoma with limited PC.
Objective: To evaluate the 6-month disease control rate (DCR) of complete CRS combined with N-IPEC and systemic chemotherapy for gastric adenocarcinoma with limited PC.
Patients and methods: Patients having gastric adenocarcinoma with PCI ≤ 10 (Arm-A) or positive peritoneal wash cytology (CY1/P0) (Arm-B) will be enrolled. Patients with other distant metastasis, including brain, lung, liver, bone, will be excluded. All patients should undergo ≥ D2 gastrectomy and complete CRS followed by N-IPEC (paclitaxel\] and systemic chemotherapy (high-dose fluorouracil and cisplatin \[P-HDFL\], or capecitabine and oxaliplatin \[CAPOX\]). N-IPEC (paclitaxel) will be administered in combination with systemic P-HDFL or CAPOX on day 1,8,15 or day 1,8 for each cycle, respectively. The disease status will be evaluated every 12 weeks based on the computed tomography scan, and the clinical evaluation (outpatient follow-up) will be performed every 2 weeks for whom receiving P-HDFL and every 3 weeks for whom receiving CAPOX. Patients will receive maximal 6 cycles N-IPEC with P-HDFL or 8 cycles N-IPEC with CAPOX. After N-IPEC is discontinued, P-HDFL or CAPOX will be continued alone until disease progression or death. The primary endpoint of this study is 6-month DCR, and the secondary endpoints include 6-month response rate for ascites, 1-year progression-free survival (PFS) and overall survival (OS), 3-year PFS and OS, and safety profiles. Based on Simon's minimax two-stage design, this trial will be carried out in two stages. In stage I, a total number of 13 (Arm-A) / 16 (Arm-B) patients is accrued. If there are ≤ 6 (Arm-A) / ≤ 14 (Arm-B) progression-free among these 13 (Arm-A) / 16 (Arm-B) patients, the study will be early stopped. Otherwise, additional 17 (Arm-A) / 2 (Arm-B) patients will be accrued in stage II, resulting in a total number sample size of 30 (Arm-A) / 18 (Arm-B).
Expected result: A ≥ 75% (Arm-A) / ≥ 95% (Arm-B) 6-month DCR could be achieved for gastric adenocarcinoma patients with limited PC (Arm-A) / with CY1P0 (Arm-B) via this treatment strategy (complete CRS + N-IPEC + P-HDFL or CAPOX) -i.e., if there are ≥ 21 (Arm-A) / ≥ 16 (Arm-B) progression-free among the 30 (Arm-A) / 18 (Arm-B) enrolled patients, we will reject the null hypothesis and claim that the treatment is promising.
Age 20 to 75 years old.
White blood cells > 4,000/mm3, neutrophils > 1,500/mm3, platelets > 100,000/mm3.
Serum creatinine < 1.5 mg/dl or creatinine clearance > 60 ml/min.
Serum bilirubin < 2 mg/dl.
Prior malignancy within 3 years or with detectable signs of recurrence.
Newly diagnosed gastric adenocarcinoma having been treated by preoperative systemic or intraperitoneal chemotherapy.
Presence of comorbidities, including liver cirrhosis (≥ Child B), decompensated heart failure (New York Heart Association [NYHA] Class III or IV congestive heart failure), poorly-controlled chronic obstructive pulmonary disease.
≥ American Society of Anesthesiologists Classification (ASA Class) Class 3.
Single group
CRS followed by IP and systemic chemotherapies
Other interventionComplete cytoreductive surgery (CRS) + normothermic intraperitoneal chemotherapy (N-IPEC) + systemic chemotherapy
6-month disease control rate
The 6-month disease control rate is defined as the percentage of patients with no occurrence of radiological PD (per RECIST 1.1), clinical PD (based on investigator's judgement), or death from any cause, after 24 weeks (\~ 6 months) from the beginning of combined IP and systemic chemotherapies.
Progression-free survival (PFS)
The 1-year and 3-year PFS, defined as the time from the date of enrollment until the date of PD or death from any cause, whichever is earliest, during the first and the first three years of the study, respectively.
Overall survival (OS)
The 1-year and 3-year OS, defined as the time from the date of enrollment until the date of death from any cause, during the first and the first three years of the study, respectively.
6-month response rate for ascites.
The 6-month response rate for ascites: the percentage of patients with complete disappearance (CR-ascites) or a dramatic decrease in ascites (PR-ascites) at the time when the 6-month disease control rate is evaluated.
Safety evaluation
Safety endpoints, including surgery-related complications, toxicities of chemotherapy, and intraperitoneal port/catheter-related complications, will be evaluated throughout the treatment period (at every follow-up visit), and then 30 days and 90 days after the treatment period is discontinued.
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