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

Sponsor
Fundacion CRIS de Investigación para Vencer el Cáncer
Study ID
NCT03425201
Phase
PHASE1/PHASE2
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Niraparib plus Cabozantinib — DRUG
    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.

Study Details

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.

Key Dates

Start date
Oct 14, 2019
Status verified
Dec 2024
Primary completion
Jul 31, 2024
Completion
Jul 31, 2024

Study Design

Enrollment
67 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER

Arms

  • 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.

Primary Outcome Measure

Phase I: maximum tolerated dose [ Time Frame: up to 1 month ]

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