Maintenance with niraparib in patients with stage III, stage IV, chemo-naïve recurrent or platinum-sensitive recurrent uterine serous carcinoma: study protocol for a phase II clinical trial.

introductionUterine serous carcinoma (USC) accounts for 40% of endometrial cancer-related deaths. The standard of care for stages III and IV USC yields a 20%-30% survival at 2 years and a 10%-20% survival at 3-5 years. Recent advances in the second-line treatment of advanced or recurrent USC are rapidly evolving. Targeted therapeutic approaches with the use of lenvatinib plus pembrolizumab, as well as the use of trastuzumab deruxtecan, offer new hope for successful second-line therapies for patients. However, further investigation into novel targeted therapeutic approaches is warranted, given the high burden of disease associated with this aggressive histological subtype. USC shares clinical and genomic similarities with epithelial ovarian cancer, suggesting a correlation with 'BRCAness'. Niraparib, a potent PARP1 and PARP2 inhibitor, was shown to have a positive impact on platinum-sensitive recurrent ovarian cancer, regardless of the presence or absence of BRCA status. Our hypothesis is that patients with stage III, stage IV and platinum-sensitive recurrent USC receiving niraparib maintenance in addition to standard therapy for USC may have an improved progression-free survival. METHODS AND ANALYSIS: Participating sites include the primary site, Northwell Health Zucker Cancer Centre, and secondary site, Rutgers Cancer Institute of NJ. Females over the age of 18 with stage III, stage IV or platinum-sensitive recurrent USC will be recruited and enrolled based on inclusion/exclusion criteria. 24 subjects will be enrolled during phase 1 and 21 subjects will be enrolled during phase 2, over a total of 3 years. Patients will receive an individualised dose of niraparib daily every 28 days per cycle for 1 year or until progression of disease. Follow-up of disease status will continue for 5 years poststudy treatment. This phase II clinical trial will employ a Simon two-stage minimax design to test the null hypothesis that the 1 year response rate is <20% versus the alternative hypothesis that the 1 year response rate is ≥40%, with alpha=0.05 and power=0.90. ETHICS AND DISSEMINATION: Ethical approval was granted by Northwell Health Cancer Institute institutional review board (reference number: 19-0380) and PRMS. Alongside journal publications, results will be available publicly on completion of the study as approved by the sponsor investigator. TRIAL REGISTRATION NUMBER: NCTN04080284.