NCT03425201: NICARAGUA

Niraparib in Combination with Cabozantinib (XL184) in Patients with Advanced Urothelial Cancer (NICARAGUA)

Completed Phase 1, PHASE2 Last updated 31 December 2024

What this trial tests

Phase 1, PHASE2 trial testing Niraparib plus Cabozantinib in Urothelial Cancer in 67 participants. Completed in 31 July 2024.

Timeline

14 October 2019

Primary endpoint
31 July 2024

31 July 2024

Quick facts

Lead sponsor	Fundacion CRIS de Investigación para Vencer el Cáncer
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	other
Enrollment	67
Start date	14 October 2019
Primary completion	31 July 2024
Estimated completion	31 July 2024
Sites	10 locations across Spain

Drugs / interventions tested

• Niraparib plus Cabozantinib — full drug profile →

Conditions studied

• Urothelial Cancer — all drugs for Urothelial Cancer →

Sponsor

Fundacion CRIS de Investigación para Vencer el Cáncer — full company profile →

Who can join

18 and older, any sex, with Urothelial Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. PARP inhibitors: enhancing efficacy through rational combinations.
   Bhamidipati D, Haro-Silerio JI, Yap TA, Ngoi N. · · 2023 · cited 118× · PMID 37430137 · DOI 10.1038/s41416-023-02326-7
2. BDNF and its signaling in cancer.
   Malekan M, Nezamabadi SS, Samami E, Mohebalizadeh M, et al · · 2023 · cited 48× · PMID 36173463 · DOI 10.1007/s00432-022-04365-8
3. Does Axl have potential as a therapeutic target in pancreatic cancer?
   Du W, Brekken RA. · · 2018 · cited 25× · PMID 30244621 · DOI 10.1080/14728222.2018.1527315
4. Therapeutic implications of germline vulnerabilities in DNA repair for precision oncology.
   Shah SM, Demidova EV, Lesh RW, Hall MJ, et al · · 2022 · cited 16× · PMID 35051883 · DOI 10.1016/j.ctrv.2021.102337
5. Combination of Talazoparib and Palbociclib as a Potent Treatment Strategy in Bladder Cancer.
   Klein FG, Granier C, Zhao Y, Pan Q, et al · · 2021 · cited 14× · PMID 33923231 · DOI 10.3390/jpm11050340
6. Genomics and Immunomics in the Treatment of Urothelial Carcinoma.
   Mollica V, Massari F, Rizzo A, Ferrara R, et al · · 2022 · cited 10× · PMID 35621673 · DOI 10.3390/curroncol29050283
7. Cabozantinib combination therapy for the treatment of solid tumors: a systematic review.
   Castellano D, Apolo AB, Porta C, Capdevila J, et al · · 2022 · cited 6× · PMID 35923927 · DOI 10.1177/17588359221108691
8. PSPC1 Inhibition Synergizes with Poly(ADP-ribose) Polymerase Inhibitors in a Preclinical Model of BRCA-Mutated Breast/Ovarian Cancer.
   Ghosh M, Kang MS, Katuwal NB, Hong SD, et al · · 2023 · cited 5× · PMID 38069409 · DOI 10.3390/ijms242317086