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

Sponsor
Principia Biopharma, a Sanofi Company (Industry)
Overall Status
Terminated
CT.gov ID
NCT02608125
Collaborator
(none)
45
Enrollment
12
Locations
1
Arm
55.9
Actual Duration (Months)
3.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

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 Design

Study Type:
Interventional
Actual Enrollment :
45 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Oct 28, 2015
Actual Primary Completion Date :
Jun 23, 2020
Actual Study Completion Date :
Jun 23, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: PRN1371

Drug: PRN1371

Drug: PRN1371

Outcome Measures

Primary Outcome Measures

  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 Outcome Measures

  1. Pharmacokinetic profile of PRN1371 including area under the serum concentration-time curve [Days 1 and 15]

  2. Pharmacokinetic profile of PRN1371 including maximum serum concentration [Days 1 and 15]

  3. Pharmacokinetic profile of PRN1371 including time to maximum serum concentration [Days 1 and 15]

  4. Pharmacodynamic profile of PRN1371 including the effect of PRN1371 on phosphate levels [While being treated with PRN1371 (expected average of 16 weeks)]

  5. Pharmacodynamic profile of PRN1371 including the effect of PRN1371 on calcium levels [While being treated with PRN1371 (expected average of 16 weeks)]

  6. 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)]

  7. 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)]

  8. Duration of response in patients treated with PRN1371 [Every 8 weeks while being treated with PRN1371 (expected average 16 weeks)]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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).

Contacts and Locations

Locations

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

Sponsors and Collaborators

  • Principia Biopharma, a Sanofi Company

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Principia Biopharma, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT02608125
Other Study ID Numbers:
  • PRN1371-001
First Posted:
Nov 18, 2015
Last Update Posted:
Dec 24, 2020
Last Verified:
Dec 1, 2020
Keywords provided by Principia Biopharma, a Sanofi Company
FGFR
Additional relevant MeSH terms:
Carcinoma
Carcinoma, Transitional Cell

Study Results

No Results Posted as of Dec 24, 2020