This is a multi-center, open label, non-randomized Phase 1 study, to be conducted in two parts, Part A, and Part B. Part A in solid tumors included the dose escalation phase for evaluating the safety and tolerability profile of PRN1371, a FGFR 1-4 Kinase inhibitor. Part B is the Cohort Expansion phase in patients with metastatic urothelial carcinoma to further evaluate safety and tolerability, preliminary activity, PK, and PD in patients with FGFR genetic alterations.
The protocol specifies rules for dose-limiting toxicity and a maximum tolerated dose (MTD). To gain further experience with the MTD, and/or at some lower optimal biologic dose level, an expansion cohort (Part B) enrolled patients with metastatic urothelial carcinoma with fibroblast growth factor receptor (FGFR) 1, 2, 3 or 4 genetic alterations.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
45
UCSF Helen Diller Family Comprehensive Cancer Cener
San Francisco, California, United States
Johns Hopkins Medicine
Baltimore, Maryland, United States
Wake Forest University Health Sciences Medical Center
Winston-Salem, North Carolina, United States
Tennessee Oncology, Sarah Canon Research Institute
Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital
Barcelona, Spain
Hospital General Universitario de Elche
Elche, Spain
Hospital Universitario Ramon y Cajal
Madrid, Spain
START Madrid-FJD Fundacion Jiminez Diaz
Madrid, Spain
Hospital Universitario 12 de Octubre
Madrid, Spain
...and 2 more locations
Incidence of treatment related Grade 3 and/or Grade 4 adverse events, defined as dose limiting toxicities, for the doses of PRN1371
Time frame: 28 days on average
Pharmacokinetic profile of PRN1371 including area under the serum concentration-time curve
Time frame: Days 1 and 15
Pharmacokinetic profile of PRN1371 including maximum serum concentration
Time frame: Days 1 and 15
Pharmacokinetic profile of PRN1371 including time to maximum serum concentration
Time frame: Days 1 and 15
Pharmacodynamic profile of PRN1371 including the effect of PRN1371 on phosphate levels
Time frame: While being treated with PRN1371 (expected average of 16 weeks)
Pharmacodynamic profile of PRN1371 including the effect of PRN1371 on calcium levels
Time frame: While being treated with PRN1371 (expected average of 16 weeks)
Pharmacodynamic profile of PRN1371 including the effect of PRN1371 on serum FGF23 (Part A only) levels
Time frame: While being treated with PRN1371 (expected average of 16 weeks)
Objective response rate (ORR) as measured by RECIST v1.1 in patients treated with PRN1371
Time frame: Every 8 weeks while being treated with PRN1371 (expected average of 16 weeks)
Duration of response in patients treated with PRN1371
Time frame: Every 8 weeks while being treated with PRN1371 (expected average 16 weeks)
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