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

Phase 1

Terminated

• Conditions: Solid Tumors; Metastatic Urothelial Carcinoma & Renal Pelvis & Ureter
• Interventions: Drug: PRN1371

• Registration Number: NCT02608125
• Lead Sponsor: Principia Biopharma, a Sanofi Company

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.

Study Timeline

• Study First Submitted: 2015-09-18
• Study Start: 2015-10-28
• Study First Submitted QC: 2015-11-16
• Study First Posted: 2015-11-18
• Primary Completion: 2020-06-23
• Study Completion: 2020-06-23
• Status Verified: 2020-12
• Last Update Submitted: 2020-12-23
• Last Update Posted: 2020-12-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 45

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PRN1371	PRN1371	Drug: PRN1371

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Pharmacokinetic profile of PRN1371 including area under the serum concentration-time curve	Days 1 and 15
Pharmacokinetic profile of PRN1371 including time to maximum serum concentration	Days 1 and 15
Pharmacodynamic profile of PRN1371 including the effect of PRN1371 on phosphate levels	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	Every 8 weeks while being treated with PRN1371 (expected average of 16 weeks)
Duration of response in patients treated with PRN1371	Every 8 weeks while being treated with PRN1371 (expected average 16 weeks)
Pharmacokinetic profile of PRN1371 including maximum serum concentration	Days 1 and 15
Pharmacodynamic profile of PRN1371 including the effect of PRN1371 on calcium levels	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	While being treated with PRN1371 (expected average of 16 weeks)

Trial Locations

Locations (12)

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 Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital General Universitario de Elche; 🇪🇸 Elche, Spain

Hospital Universitario Ramon y Cajal; 🇪🇸 Madrid, Spain

Hospital Virgen del Rocio; 🇪🇸 Seville, Spain

START Madrid-CIOCC, Centro Integral Oncológico Clara Campal; 🇪🇸 Madrid, Spain

START Madrid-FJD Fundacion Jiminez Diaz; 🇪🇸 Madrid, Spain