A Dose Escalation Study in Solid Tumors and a Dose Expansion Study of PRN1371 in Adult Patients With Metastatic Urothelial Carcinoma

Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02608125
• Other study ID #: PRN1371-001
• Status: Terminated
• Phase: Phase 1
• Start date: October 28, 2015
• Est. completion date: June 23, 2020

Study information

• Verified date: December 2020
• Source: Principia Biopharma Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 45
• Est. completion date: June 23, 2020
• Est. primary completion date: June 23, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Metastatic Urothelial Carcinoma & Renal Pelvis & Ureter
• Solid Tumors

Intervention

Drug:
• PRN1371

Locations

Country	Name	City	State
Spain	Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital	Barcelona
Spain	Hospital General Universitario de Elche	Elche
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	START Madrid-CIOCC, Centro Integral Oncológico Clara Campal	Madrid
Spain	START Madrid-FJD Fundacion Jiminez Diaz	Madrid
Spain	Hospital Virgen del Rocio	Seville
United States	Johns Hopkins Medicine	Baltimore	Maryland
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Tennessee Oncology, Sarah Canon Research Institute	Nashville	Tennessee
United States	UCSF Helen Diller Family Comprehensive Cancer Cener	San Francisco	California
United States	Wake Forest University Health Sciences Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Principia Biopharma Inc.

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment related Grade 3 and/or Grade 4 adverse events, defined as dose limiting toxicities, for the doses of PRN1371		28 days on average
Secondary	Pharmacokinetic profile of PRN1371 including area under the serum concentration-time curve		Days 1 and 15
Secondary	Pharmacokinetic profile of PRN1371 including maximum serum concentration		Days 1 and 15
Secondary	Pharmacokinetic profile of PRN1371 including time to maximum serum concentration		Days 1 and 15
Secondary	Pharmacodynamic profile of PRN1371 including the effect of PRN1371 on phosphate levels		While being treated with PRN1371 (expected average of 16 weeks)
Secondary	Pharmacodynamic profile of PRN1371 including the effect of PRN1371 on calcium levels		While being treated with PRN1371 (expected average of 16 weeks)
Secondary	Pharmacodynamic profile of PRN1371 including the effect of PRN1371 on serum FGF23 (Part A only) levels		While being treated with PRN1371 (expected average of 16 weeks)
Secondary	Objective response rate (ORR) as measured by RECIST v1.1 in patients treated with PRN1371		Every 8 weeks while being treated with PRN1371 (expected average of 16 weeks)
Secondary	Duration of response in patients treated with PRN1371		Every 8 weeks while being treated with PRN1371 (expected average 16 weeks)