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

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

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.

Study Overview

• Status: Terminated
• Conditions: Solid Tumors; Metastatic Urothelial Carcinoma & Renal Pelvis & Ureter
• Intervention / Treatment: Drug: PRN1371

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 Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital
  • Elche, Spain, 03203
    • Hospital General Universitario de Elche
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28040
    • START Madrid-FJD Fundacion Jiminez Diaz
  • Madrid, Spain, 28050
    • START Madrid-CIOCC, Centro Integral Oncológico Clara Campal
  • Seville, Spain, 41013
    • Hospital Virgen del Rocío
• United States
  • California
    • San Francisco, California, United States, 94115
      • UCSF Helen Diller Family Comprehensive Cancer Cener
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins Medicine
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, Sarah Canon Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRN1371; Drug: PRN1371	Drug: PRN1371

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
Pharmacokinetic profile of PRN1371 including area under the serum concentration-time curve	Days 1 and 15
Pharmacokinetic profile of PRN1371 including maximum serum concentration	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)
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)
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)

Collaborators and Investigators

• Sponsor: Principia Biopharma, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2015
• Primary Completion (Actual): June 23, 2020
• Study Completion (Actual): June 23, 2020

Study Registration Dates

• First Submitted: September 18, 2015
• First Submitted That Met QC Criteria: November 16, 2015
• First Posted (Estimate): November 18, 2015

Study Record Updates

• Last Update Posted (Actual): December 24, 2020
• Last Update Submitted That Met QC Criteria: December 23, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: FGFR
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell
• Other Study ID Numbers: PRN1371-001