A Phase I Dose-Escalation Study Of Intraperitoneal (Ip) Cisplatin, Iv/Ip Paclitaxel, Iv Bevacizumab, And Oral Olaparib For Newly Diagnosed Adenxal Carcinoma.

5572 Background: IP cisplatin (Cis) plus IV/IP paclitaxel (Tax) is a standard therapy for optimally debulked adnexal cancer. We previously demonstrated the feasibility of combining bevacizumab (Bev) with this IV/IP regimen. In this study IP Cis, IV/IP Tax, and IV Bev are combined with olaparib (Ola) as front-line therapy. Methods: Patients with newly diagnosed adnexal (ovarian, fallopian tube, or primary peritoneal) carcinoma, acceptable organ function, and KPS ≥ 70% are eligible. Patients receive 6 cycles of chemotherapy plus Bev: Tax 135 mg/m 2 IV over 3 hours on Day 1, Bev 15 mg/kg IV on Day 1 (starting cycle 2), Cis 75 mg/m 2 IP on Day 2, Tax 60 mg/m 2 IP on Day 8. Bev is continued every 3 weeks for 21 treatments after chemotherapy is complete. In addition, Ola is given at escalating doses (50/100/200mg tabs BID) on Days 2-8 during cycles 1-6, and then 300mg BID Daily during cycles 7-22. The primary objective is to evaluate the MTD and safety/tolerability of Ola when combined with IP Cis, IV Bev and IV/IP Tax using a 3+3 dose escalation scheme. Results: Seventeen women have been treated [median age 57 (47-73)]: 8 in cohort 1 (50mg), 3 in cohort 2 (100mg) and 6 in cohort 3 (200mg). Thirteen (76%) completed all 6 cycles of IV/IP cis/tax; 2 (12%) experienced IP port malfunction (both were removed and replaced); 2 (12%) switched from IP Cis to IV carboplatin due to nephrotoxicity (via ATN and/or OCT-2 inhibition). Grade 3/4 toxicities have included: neutropenia (50%), hyperglycemia (12.5%), leukopenia (12.5%), anemia (18.8%), fatigue (12.5%), and lymphopenia (31.3%). There were 2 occurrences of related grade 3 small bowel obstructions (12.5%), during cycles 2 and 7, respectively. There were no perforations or fistulae. Maintenance therapy with Bev + Ola was generally well tolerated. Conclusions: The addition of Ola to this IV/IP regimen appears to be feasible. Ola may increase the risk of creatinine elevation and myelotoxicity. The MTD of intermittent dosing of Ola tabs concurrent with chemotherapy appears to be 200mg BID, while maintenance bev + full-dose ola at 300mg BID continuous appears feasible following IV/IP. Updated results will be presented. Clinical trial information: NCT02121990.