Phase Ii Evaluation Of Nintedanib In The Treatment Of Bevacizumab-Resistant Persistent/Recurrent Ovarian, Fallopian Tube, Or Primary Peritoneal Carcinoma.

TPS5601 Background: Anti-angiogenic therapy with bevacizumab (B) has shown promise in the treatment of advanced/recurrent epithelial ovarian cancer (EOC) however, the development of resistance against B-induced VEGF blockade may occur via secondary pathways. Data suggest that continued VEGF inhibition after progression may have utility in the management of B-treated patients. Nintedanib is a tyrosine kinase inhibitor that inhibits both the VEGF pathway & secondary pro-angiogenic pathways. In EOC, nintedanib has shown activity in the upfront setting when combined with standard chemotherapy. Methods: This is an open label multi-center study. The primary objective of this study is to assess the activity of nintedanib as measured by 6 month progression free survival (PFS) in patients with B-resistant, persistent/recurrent EOC, fallopian tube (FTC), or primary peritoneal carcinoma (PPC). Secondary objectives include tumor response based on RECIST 1.1 & Gynecologic Cancer Intergroup (GCIG) CA125 criteria, the frequency/severity of AE, & duration of PFS. Patient preferences for treatment outcomes & assessment of baseline quality of life (QOL) & cancer related symptoms will be performed. Translational objectives include evaluation of VEGF & growth factor levels to assess for correlation with outcomes as well as coagulation/endothelial cell activation markers that may predict treatment-related thrombotic/bleeding risk. Patients must have recurrent/persistent EOC, FTC or PPC with measurable/detectable disease and be B-resistant (treatment free interval after B response < 6 months or progression on B containing therapy) and have ≤ 3 prior cytotoxic regimens (including 1 platinum-based). Patients with prior radiation for non-EOC tumors, therapeutic anticoagulation, history of abdominal fistula/GI perforation, nonhealing ulcers, CNS disease or suspicion of transmural bowel involvement are excluded. Nintedanib is dosed at 200mg BID until progression or AE preclude therapy. Each cycle is 28 days. Blood/urine specimens are collected at pre-determined intervals. At this time, seventeen out of 27 patients planned for the first stage have been enrolled. Clinical trial information: NCT01669798.