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Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>This Phase I study evaluated the safety and tolerability of concurrent niraparib, an oral poly(ADP-ribose) polymerase (PARP) 1\/2 inhibitor, with definitive radiotherapy in women with locally advanced or platinum-sensitive metastatic cervical cancer. Dose escalation followed a Bayesian Optimal Interval (BOIN) design with a target dose-limiting toxicity (DLT) rate of 30%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Women \u226518 years with FIGO stage IIIC2 (bulky nodes &amp;gt;1 cm) or stage IV cervical cancer demonstrating response to platinum-based induction chemotherapy were eligible. Niraparib 100 mg was administered daily concurrent with pelvic radiotherapy (45\u201357.5 Gy via IMRT with nodal boosts) and brachytherapy, continuing 28 days post-radiation. Per the BOIN design, dose escalation occurred if the observed DLT rate fell below the pre-specified boundary of 0.2365; de-escalation occurred if it exceeded 0.3585. DLTs were defined per protocol as grade \u22654 non-hematologic toxicity, grade 4 thrombocytopenia \u226514 days, grade 3\u20134 thrombocytopenia with bleeding, or toxicity causing &amp;gt;28-day niraparib delay or &amp;gt;2-day radiation delay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Four patients were enrolled at the 100 mg dose level before study closure due to slow accrual and anticipated changes in standard of care. Two patients (NVX-1, NVX-4) completed concurrent niraparib without protocol-defined DLT. Two patients (NVX-2, NVX-3) discontinued niraparib due to treatment-limiting grade 2 thrombocytopenia (CTCAE v4.0; nadirs 71,000\/\u03bcL and 53,000\/\u03bcL); these events did not meet protocol DLT criteria, and no bleeding occurred. The observed DLT rate of 0\/4 (0%) fell below the escalation boundary; however, the study closed before dose escalation. Both patients who discontinued had baseline platelet counts &amp;lt;150,000\/\u03bcL and significant comorbidities (HIV\/cirrhosis; suspected chemotherapy-related marrow injury), whereas the two who completed therapy had counts &amp;gt;250,000\/\u03bcL. All patients completed radiotherapy and achieved local disease control at minimum 12-month follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Concurrent niraparib 100 mg with pelvic radiotherapy was feasible without protocol-defined DLTs. Treatment-limiting grade 2 thrombocytopenia occurred in patients with identifiable risk factors including low baseline platelet counts, hepatic dysfunction, and low body weight. These hypothesis-generating findings support further investigation with attention to patient selection criteria in future trials combining PARP inhibitors with radiotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1677424","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T06:47:49Z","timestamp":1773038869000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Phase I study of niraparib with radiotherapy for treatment of metastatic and locally advanced invasive carcinoma of the cervix (NIVIX)"],"prefix":"10.3389","volume":"16","author":[{"given":"Piyush","family":"Pathak","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Baylor College of Medicine","place":["Houston, TX, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eunji","family":"Jo","sequence":"additional","affiliation":[{"name":"Department 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