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

NCT02608125 | Terminated Phase 1

• 1 other identifier: PRN1371-001
• Study Type: interventional
• Target: 45
• Locations: 2 countries
• Sites: 12

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.

Conditions

Solid Tumors; Metastatic Urothelial Carcinoma & Renal Pelvis & Ureter

Keywords

FGFR

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• 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)

Study Arms (1)

PRN1371

EXPERIMENTAL

Drug: PRN1371

Drug: PRN1371

Interventions

PRN1371 DRUG

PRN1371

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Principia Biopharma, a Sanofi Company: lead

Study Sites (12)

UCSF Helen Diller Family Comprehensive Cancer Cener

San Francisco, California, 94115, United States

Location

Johns Hopkins Medicine

Baltimore, Maryland, 21205, United States

Location

Wake Forest University Health Sciences Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Tennessee Oncology, Sarah Canon Research Institute

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital

Barcelona, 08035, Spain

Location

Hospital General Universitario de Elche

Elche, 03203, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

START Madrid-FJD Fundacion Jiminez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

START Madrid-CIOCC, Centro Integral Oncológico Clara Campal

Madrid, 28050, Spain

Location

Hospital Virgen del Rocio

Seville, 41013, Spain

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

PRN1371

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2015
• First Posted: November 18, 2015
• Study Start: October 28, 2015
• Primary Completion: June 23, 2020
• Study Completion: June 23, 2020
• Last Updated: December 24, 2020

Record last verified: 2020-12

Locations

ES (7); US (5)