Phase II trial of maintenance niraparib in patients with stage III,stage IV or platinum-sensitive recurrent uterine serous carcinoma (330)

Abstract

<b>Objectives:</b> Uterine serous carcinoma (USC) accounts for up to 40% of endometrial cancer-related deaths. Patients with USC share many genomic and clinical characteristics with serous ovarian cancer patients. This study aims to determine the efficacy of Niraparib in women with advanced or platinum-sensitive recurrent USC. We also aim to describe the safety profile of this regimen. We hypothesize that Niraparib maintenance will be a well-tolerated treatment and show a significant response in patients with USC. <b>Methods:</b> We are conducting a Phase II prospective non-randomized cohort study recruiting 45 patients with newly diagnosed stage III, IV, or platinum-sensitive recurrent USC who will receive 300 mg of Niraparib daily for one year or until disease progression. Dose reductions to 200 mg and 100 mg will be allowed based on treatment side effects. Newly diagnosed patients receive standard platinumbased treatment +/- radiation followed by Niraparib maintenance. Women with recurrent USC will receive platinum-based therapy followed by Niraparib maintenance. Platinum sensitivity is defined as achieving a complete or partial response and disease progression >6 months after completion of their last dose of platinum-based chemotherapy. Patients must have achieved a partial, stable, or complete tumor response following the last chemotherapy, minimal of 3 cycles, and physician choice of platinum-based regimen. Patients must be recruited within 12 weeks of completing chemotherapy or 14 weeks if they are receiving adjuvant radiation therapy. The primary outcome will be progression-free survival (PFS) at one year. Secondary outcomes include PFS at three years, treatment-related adverse events, quality of life measures using Functional Assessment of Cancer Therapy and EQ-5D-5L Euroqol, overall survival (OS), and overall response rate at 2 and 3 years. Mutational burden and loss of heterozygosity will be evaluated for all patients using FoundationOne testing. This trial will employ a Simon two-stage minimax design to test the null hypothesis that the one-year response rate is <20% (which would not be clinically meaningful) versus the alternative hypothesis that the one-year response rate is ≥40%. A treatment "success" will be defined as the patient being alive and progressionfree at one-year post-treatment. This design corresponds to testing the null hypothesis that the true objective response rate is 20% or less versus the alternative hypothesis that the true response rate is 40% or greater, with alpha=0.05 and power=0.90. To date, we have recruited six patients at Northwell and are opening additional sites for recruitment.