Niraparib in Combination With Cabozantinib (XL184) in Patients With Advanced Urothelial Cancer (NICARAGUA) (NICARAGUA)
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|ClinicalTrials.gov Identifier: NCT03425201|
Recruitment Status : Recruiting
First Posted : February 7, 2018
Last Update Posted : February 9, 2022
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.
|Condition or disease||Intervention/treatment||Phase|
|Urothelial Cancer||Drug: Niraparib plus Cabozantinib||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Open-label, multicenter, phase I/II dose-escalation study|
|Masking:||None (Open Label)|
|Official Title:||A Phase I-II Study to Evaluate the Efficacy and Safety of Niraparib in Combination With Cabozantinib (XL184) in Patients With Advanced Urothelial Cancer After Failure to First-line Platinum-based Chemotherapy|
|Actual Study Start Date :||October 14, 2019|
|Estimated Primary Completion Date :||April 2023|
|Estimated Study Completion Date :||October 2025|
Experimental: Niraparib plus Cabozantinib
Patients will receive niraparib and cabozantinib p.o. once daily in 28-day cycles.
In phase I, patients will be accrued to each dose level in cohorts of 6 patients. Escalation will continue until a dose-limiting toxicity (DLT) is observed or the highest dose-level is reached.
In phase II study patients will receive niraparib p.o. once daily and cabozantinib p.o. once daily in 28-day cycles at doses recommended in the phase I study.
If niraparib or cabozantinib need to be interrupted due to toxicity, patient can continue only with the other drug.
Drug: Niraparib plus Cabozantinib
Non-randomized trial will comprise 2 stages. A dose escalation phase will characterize the safety, tolerability, DLTs and MTD, of oral niraparib plus cabozantinib in patients with urothelial or renal cell carcinoma. Subsequently, the phase II will further evaluate the safety and antitumor activity of this combination in patients with urothelial carcinoma.
- Phase I: maximum tolerated dose [ Time Frame: up to 1 month ]Highest dose at which ≤1 out of 6 patients experience a DLT
- Phase II: progression free survival [ Time Frame: Up to 6 months ]Time from the date of first dose of study treatment to the date of progression or death (from any cause).
- Incidence of Treatment-Emergent Adverse Events [ Time Frame: Up to 6 months ]Number of events per patient
- Phase II: Objective Response Rate [ Time Frame: Up to 6 months ]Response according to RECIST 1.1 criteria
- Phase II: Disease Control Rate [ Time Frame: Up to 6 months ]Response according to RECIST 1.1 criteria
- Phase II: Duration of response [ Time Frame: Up to 6 months ]Time from the date of response is achieved until documented tumor progression
- Phase II: Overall Survival [ Time Frame: Up to 6 months ]Time from the date of first dose of study treatment to the date of death due to any cause
- Correlation of the activity of niraparib plus cabozantinib with the molecular profile of the tumor [ Time Frame: Up to 6 months ]Immunohistochemistry and RNA analysis of pre- and post-tumor samples
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03425201
|Contact: Albert Font, MD||+34 93 497 89 email@example.com|
|Contact: Daniel Castellano, MDfirstname.lastname@example.org|
|Xarxa Assistencial Universitària de Manresa||Recruiting|
|Barcelona, Cataluña, Spain|
|Contact: Montserrat Domenech, MD|
|Principal Investigator: Montserrat Domenech, MD|
|Contact: Albert Font|
|Contact: Begoña Mellado|
|Contact: Nuria Sala, MD|
|Principal Investigator: Nuria Sala, MD|
|L'Hospitalet De Llobregat, Spain|
|Contact: Francisco J García del Muro|
|Hospital 12 de Octubre||Recruiting|
|Contact: Daniel Castellano|
|Hospital Clinico San Carlos||Withdrawn|
|Hospital Madrid Norte Sanchinarro||Recruiting|
|Contact: Elena Sevillano Fernández, MD|
|Principal Investigator: Elena Sevillano Fernández, MD|
|Hospital Ramon y Cajal||Recruiting|
|Contact: Teresa Alonso, MD|
|Principal Investigator: Teresa Alonso, MD|
|Hospital Marques de Valdecilla||Recruiting|
|Contact: Ignacio Duran, MD|
|Principal Investigator: Ignacio Durán, MD|
|Instituto Valenciano de Oncología||Recruiting|
|Contact: Miguel A Climent|
|Principal Investigator:||Albert Font, MD||ICO Badalona-Hospital Germans Trias i Pujol|
|Principal Investigator:||Daniel Castellano, MD||Hospital 12 de Octubre|