Phase 1 Open Label Trial Of Intraperitoneal Paclitaxel (Ipp) In Combination With Intravenous Cisplatin (C) And Oral Capecitabine (X) In Patients With Advanced Gastric Cancer And Peritoneal Metastases.

4061 Background: IPP is a potential treatment option in patients with gastric cancer with peritoneal metastasis. IPP with a dose of 20 mg/m2 is well tolerated in combination with S1; however, this has been achieved in a specific genetic pool (Japanese population), and S1 is not available in some countries. We investigated the Maximum Tolerated Dose (MTD) of IPP in addition to a standard chemotherapy combination in an Australian population. Methods: Study population included synchronous or metachronous metastatic HER-2 non-amplified gastric adenocarcinoma with histologically/cytologically proven peritoneal involvement and adequate organ function. Intra-peritoneal catheter was placed surgically. 3 + 3 standard dose-escalation design was used. MTD was defined as the highest dose level at which ≤ 33% of patients had Dose Limiting Toxicity (DLT). DLT was defined within the first 3 cycles. Recommended Phase-2 Dose was defined as equal to the MTD, or cohort-3 dose if MTD was not reached. Treatment: maximum of six 21-day cycles of C (80mg/m2 IV day 1) + X (1000mg/m2 PO BD days 1-14) + IPP (days 1 and 8). IPP doses for Cohort-1, 2 and 3 were 10, 20 and 30mg/m2 respectively. Primary endpoint was the MTD of IPP. Secondary endpoints included safety, tolerability, overall response rate, ascites response rate, progression free survival and overall survival. Results: 15 patients were recruited in 3 cohorts: 9 males (60%), median age at study entry: 61y (range 32-82). All had synchronous metastatic disease and were chemo-naïve. Cohort-1 expanded to 6 patients due to 1 DLT (grade 3 diarrhea), cohort-2 included 3 patients (no DLT) and cohort-3 was expanded to 6 patients as planned and 1 DLT occurred (febrile neutropenia). MTD was not reached and Recommended Phase 2 Dose was determined as 30mg/m2. 8 patients (53%) completed all 6 cycles of treatment. The last patient on the study has completed 3 cycles and is expected to complete 6 cycles by April 2019. No grade 4 or 5 toxicity was recorded. Conclusions: MTD of IPP was not reached. IPP is safe in combination with C + X and the Recommended Phase 2 Dose is 30 mg/m2. Survival data will be presented when available. Clinical trial information: ACTRN12614001063606.