The sample-size justification is based on the exact, one-sided, binomial test of the primary endpoint, progression free survival at 12 months (viz., PFS12). Based on current evidence, PFS-12 in gastric carcinomatosis with optimal treatment is estimated at less than 10% [12 (link)] The hypothesis is that the combination of upfront systemic therapy for 3–4 months followed by IP chemotherapy for 3 months with or without CRS/HIPEC in selected patients is feasible and will improve PFS-12 compared to historical controls. Previous phase II study of iterative HIPEC reported a conversion to surgery rate of 26.3% [25 (link)]. We expect that with selection of patients after three months of systemic chemotherapy and iterative NIPEC treatment that the conversion to surgery rate will be 35% in this study. To estimate the efficacy, n = 20 patients will be enrolled. If at least n = 7 patients have not progressed by 12 months, then the observed PFS-12 of 35% will have a one sided lower 95% CI of 17.5% [26 ]. This means the lower boundary for estimated efficacy is as good as or better than currently available options in this setting. This test will have at least 80-percent power to reject the null- hypothesis that PFS12 is ten percent in favor of an alternative hypothesis that PFS12 is at least 35 percent with 20 evaluable participants. We seek to enroll 25 subjects to allow for attrition.
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