Niraparib in Combination With Cabozantinib (XL184) in Patients With Advanced Urothelial Cancer (NICARAGUA)
Status:
Recruiting
Trial end date:
2025-03-01
Target enrollment:
Participant gender:
Summary
Cabozantinib is an oral, small-molecule tyrosine kinase inhibitor. Its primary targets are
Hepatocyte growth factor receptor protein (MET), vascular endothelial growth factor receptor
1-3 (VEGFR1-3), RET, AXL, FLT3 and KIT. Cabozantinib has been approved by the FDA for
clinical treatment of progressive, metastatic medullary thyroid cancer. Recently published
trials have demonstrated activity for cabozantinib in patients with advanced renal cell
carcinoma and metastatic castration-resistant prostate cancer (mCRPC). Furthermore, in
preclinical models of urothelial carcinoma (UC) of the bladder, cabozantinib has demonstrated
the ability to inhibit tumor xenograft growth. It has been suggested that levels of soluble
Met ectodomain (sMet) can be measured in the urine as a useful biomarker to monitor the
efficacy of c-Met therapy in bladder cancer patients. Moreover, cabozantinib has demonstrated
activity in heavily pretreated, advanced bladder cancer patients, with a response rate of
19.5% and manageable toxicities.
In the phase I of this study it is proposed to evaluate DLTs of niraparib and cabozantinib
combination and determine maximum tolerated dose (MTD) in patients with advanced urothelial
or renal cell carcinoma. In the phase II it is proposed to make a preliminary evaluation of
the efficacy of this combination in patients with urothelial cell carcinoma. Efficacy results
will be correlated with genomic alterations related to c-Met and Poly [ADP-ribose] polymerase
(PARP) inhibitor activity.
Phase:
Phase 1/Phase 2
Details
Lead Sponsor:
Fundacion CRIS de Investigación para Vencer el Cáncer
Collaborators:
Apices Soluciones S.L. GlaxoSmithKline Ipsen Tesaro, Inc.