STOPGAP Trial: Intraperitoneal Chemotherapy for Gastric Cancer

IP regimen consists of IV Paclitaxel, 5- FU and Leucovorin and IP Paclitaxel (Table 2). Although in PHOENIX GC trial the IP dose was 20 mg/m2, given the safety data for higher doses of IP paclitaxel, we chose an IP dose of 40 mg/m2. However, the systemic backbone portion of the regimen used in PHOENIX GC was adopted as such with the substitution of 5-FU and leucovorin instead of S-1 as S-1 is not available in the United States.Table 2

STOPGAP intraperitoneal chemotherapy regimen

Agent	Dose	Route	Schedule
Leucovorin	20 mg/m2	IV	Days 1 and 8
5-FU	400 mg/m2	IV	Days 1 and 8
Paclitaxel	50 mg/m2	IV	Days 1and 8
Paclitaxel	40 mg/m2	IP	Days 1and 8

Paclitaxel 40 mg/m2 in 500 ml of normal saline will be instilled into the peritoneal cavity through the IP port on days 1 and 8, repeated every 21 days for 4 cycles. In patients with moderate ascites, IP port will be used to drain the fluid prior to delivery of IP treatment. Patients with significant worsening of sensory neuropathy from prior systemic treatment may omit IV Paclitaxel in subsequent cycles. Since all enrolled patients have stage IV disease, the addition of nivolumab 360 mg IV on day 1 of each cycle is permitted based on investigator discretion.
Restaging imaging with CT and /or diffusion weighted MRI with contrast is obtained 4–6 weeks after completion of IP chemotherapy. In the absence of progression, patients may undergo diagnostic laparoscopy with biopsies to assess the extent of PCI and treatment response. At this point, based on response, patients will be triaged to one of the following treatment plans: stable disease or response and PCI > 10—continue IP chemotherapy regimen, progression—switch to second line regimen, response with PCI $\le$ 10 and complete cytoreduction is feasible—recommend cytoreduction surgery with HIPEC. Although the CYTOCHIP study showed long term survival benefit was achieved with CRS/HIPEC in patients with PCI ≤ 7, we chose a cutoff of PCI ≤ 10, as the objective of the STOPGAP study is to offer cytoreduction to all eligible patients who have low volume disease in whom a complete cytoreduction is feasible. This is particularly important as the likelihood of prolonged progression free survival without CRS in gastric PC is unlikely. HIPEC is performed using Cisplatin 75 mg/m2 and Mitomycin15 mg/m2 for 90 min at temperature between 41–42 °C. Adjuvant therapy is given based on the discretion of the treating investigator. Routine surveillance with CT scan of the chest, abdomen, and pelvis and/or MRI will be performed every 8–12 weeks. Radiological assessment of disease recurrence will be monitored. Quality of life questionnaire, EQ-5D-5L will be completed by patient every 8 weeks.