Clinical trial NCT02608125: A Dose Escalation Study in Solid Tumors and a Dose Expansion Study of PRN1371 in Adult Patients With Metastatic Urothelial Carcinoma
Official title: A Phase I Open-Label, Multicenter, Dose-Escalation Study of PRN1371, a FGFR 1-4 Kinase Inhibitor, in Adult Patients With Advanced Solid Tumors, Followed by an Expansion Cohort in Patients With Metastatic Urothelial Carcinoma With FGFR 1, 2, 3, or 4 Genetic Alterations
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumors
Metastatic Urothelial Carcinoma & Renal Pelvis & Ureter
Keywords: FGFR
Lead sponsor: Principia Biopharma, a Sanofi Company
Sponsor class: INDUSTRY
First posted: 2015-11-18
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Histological or cytological documentation of an advanced solid tumor
* Subject must have metastatic or recurrent disease and have failed first-line systemic treatment, and if indicated, failed approved second-line therapy, and for whom no standard therapy options are anticipated to result in a durable remission
* Subject must have evaluable, progressive, and measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, Version 1.1
* Adequate bone marrow, liver, and renal function
* Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

For Part B (expansion) in subjects metastatic urothelial carcinoma:

* The patient's tumor has been evaluated and prospectively identified as having FGFR 1, 2, 3, or 4 genetic alterations.

Exclusion Criteria:

* Patients who have received adequate prior treatment with a highly selective FGFR inhibitor
* Patients with other major uncontrolled medical conditions, e.g., recent myocardial infarction, stroke, diabetes, active hepatitis
* Patients who have received prior systemic anticancer therapy ≤ 3 weeks prior to study start (6 weeks for nitrosourea, antibodies, or mitomycin-C)
* Patients diagnosed with another primary malignancy within 3 years prior to study start, with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma, or other non-melanomatous skin cancer, or carcinoma in situ of the uterine cervix
* Patients with glioblastoma multiforme
* Patient has a primary neoplasm of the brain or known uncontrolled metastases to the central nervous system (CNS).

Primary outcomes:
measure: Incidence of treatment related Grade 3 and/or Grade 4 adverse events, defined as dose limiting toxicities, for the doses of PRN1371
timeFrame: 28 days on average
Secondary outcomes:
measure: Pharmacokinetic profile of PRN1371 including area under the serum concentration-time curve
timeFrame: Days 1 and 15
measure: Pharmacokinetic profile of PRN1371 including maximum serum concentration
timeFrame: Days 1 and 15
measure: Pharmacokinetic profile of PRN1371 including time to maximum serum concentration
timeFrame: Days 1 and 15
measure: Pharmacodynamic profile of PRN1371 including the effect of PRN1371 on phosphate levels
timeFrame: While being treated with PRN1371 (expected average of 16 weeks)
measure: Pharmacodynamic profile of PRN1371 including the effect of PRN1371 on calcium levels
timeFrame: While being treated with PRN1371 (expected average of 16 weeks)
measure: Pharmacodynamic profile of PRN1371 including the effect of PRN1371 on serum FGF23 (Part A only) levels
timeFrame: While being treated with PRN1371 (expected average of 16 weeks)
measure: Objective response rate (ORR) as measured by RECIST v1.1 in patients treated with PRN1371
timeFrame: Every 8 weeks while being treated with PRN1371 (expected average of 16 weeks)
measure: Duration of response in patients treated with PRN1371
timeFrame: Every 8 weeks while being treated with PRN1371 (expected average 16 weeks)
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Cener
state: California
city: Baltimore
country: United States
facility: Johns Hopkins Medicine
state: Maryland
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences Medical Center
state: North Carolina
city: Nashville
country: United States
facility: Tennessee Oncology, Sarah Canon Research Institute
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Barcelona
country: Spain
facility: Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: START Madrid-FJD Fundacion Jiminez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: START Madrid-CIOCC, Centro Integral Oncológico Clara Campal
city: Seville
country: Spain
facility: Hospital Virgen del Rocio
Study officials:
References: