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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

NCT02608125

Description:

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 is 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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Dose Escalation Study in Solid Tumors and a Dose Expansion Study of PRN1371 in Adult Patients With Metastatic Urothelial Carcinoma
  • 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 IDs

  • ORG STUDY ID: PRN1371-001
  • NCT ID: NCT02608125

Conditions

  • Solid Tumors
  • Metastatic Urothelial Carcinoma & Renal Pelvis & Ureter

Interventions

DrugSynonymsArms
PRN1371PRN1371

Purpose

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 is 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 study is a dose escalation study. 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) will be enrolled in patients
      with metastatic urothelial carcinoma with fibroblast growth factor receptor (FGFR) 1, 2, 3 or
      4 genetic alterations.
    

Trial Arms

NameTypeDescriptionInterventions
PRN1371ExperimentalDrug: PRN1371
  • PRN1371

Eligibility Criteria

        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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of treatment related Grade 3 and/or Grade 4 adverse events, defined as dose limiting toxicities, for the doses of PRN1371
Time Frame:28 days on average
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Pharmacokinetic profile of PRN1371 including area under the serum concentration-time curve
Time Frame:Days 1 and 15
Safety Issue:
Description:
Measure:Pharmacokinetic profile of PRN1371 including maximum serum concentration
Time Frame:Days 1 and 15
Safety Issue:
Description:
Measure:Pharmacokinetic profile of PRN1371 including time to maximum serum concentration
Time Frame:Days 1 and 15
Safety Issue:
Description:
Measure:Pharmacodynamic profile of PRN1371 including the effect of PRN1371 on phosphate levels
Time Frame:While being treated with PRN1371 (expected average of 16 weeks)
Safety Issue:
Description:
Measure:Pharmacodynamic profile of PRN1371 including the effect of PRN1371 on calcium levels
Time Frame:While being treated with PRN1371 (expected average of 16 weeks)
Safety Issue:
Description:
Measure:Pharmacodynamic profile of PRN1371 including the effect of PRN1371 on serum FGF23 levels
Time Frame:While being treated with PRN1371 (expected average of 16 weeks)
Safety Issue:
Description:
Measure:Objective response rate (ORR) as measured by RECIST v1.1 in patients treated with PRN1371
Time Frame:Every 8 weeks while being treated with PRN1371 (expected average of 16 weeks)
Safety Issue:
Description:
Measure:Duration of response in patients treated with PRN1371
Time Frame:Every 8 weeks while being treated with PRN1371 (expected average 16 weeks)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Principia Biopharma Inc.

Trial Keywords

  • FGFR

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