Clinical Trials /

A Study of TAS-120 in Patients With Advanced Solid Tumors

NCT02052778

Description:

This is an open-label, nonrandomized, Phase 1 dose-escalation, dose-expansion, and Phase 2 study targeting tumors with FGF/FGFR aberrations. The purpose of the study is to evaluate the safety, tolerability, PK, pharmacodynamic, and anti-tumor activity of TAS-120 in patients with advanced solid tumors with and without FGF/FGFR-related abnormalities. The study will be conducted in 3 parts, (1) Dose escalation to determine the MTD and/ or RP2D of TAS-120 in which this part of the study has been completed; (2) Phase 1 expansion to further evaluate the safety and efficacy of RP2D of TAS-120 in patients with tumors harboring specific FGFR aberrations, specifically in patients with cholangiocarcinoma, gliomas , urothelial carcinomas and any other tumors with FGFR fusion or activating mutation or amplification. Up to approximately 185 patients will be enrolled in the phase 1 expansion; and (3) Phase 2 study to confirm ORR of TAS-120 in intra-hepatic CCA patients with tumors harboring FGFR2 gene fusions. Approx. 100 patients will be enrolled in phase 2.

Related Conditions:
  • Anaplastic Astrocytoma
  • Anaplastic Oligodendroglioma
  • Extrahepatic Cholangiocarcinoma
  • Glioblastoma
  • Intrahepatic Cholangiocarcinoma
  • Malignant Solid Tumor
  • Multiple Myeloma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of TAS-120 in Patients With Advanced Solid Tumors
  • Official Title: Phase 1/2 Study of TAS-120 in Patients With Advanced Solid Tumors Harboring FGF/FGFR Aberrations

Clinical Trial IDs

  • ORG STUDY ID: TPU-TAS-120-101
  • SECONDARY ID: 2013-004810-16
  • NCT ID: NCT02052778

Conditions

  • Cholangiocarcinoma
  • Brain Tumor
  • Urothelial Cancer
  • Other Tumor Types With FGFR2 Gene Fusions
  • Activating Mutations
  • FGFR2 Amplification

Interventions

DrugSynonymsArms
TAS-120TAS-120

Purpose

This is an open-label, nonrandomized, Phase 1 dose-escalation, dose-expansion, and Phase 2 study targeting tumors with FGF/FGFR aberrations. The purpose of the study is to evaluate the safety, tolerability, PK, pharmacodynamic, and anti-tumor activity of TAS-120 in patients with advanced solid tumors with and without FGF/FGFR-related abnormalities. The study will be conducted in 3 parts, (1) Dose escalation to determine the MTD and/ or RP2D of TAS-120 in which this part of the study has been completed; (2) Phase 1 expansion to further evaluate the safety and efficacy of RP2D of TAS-120 in patients with tumors harboring specific FGFR aberrations, specifically in patients with cholangiocarcinoma, gliomas , urothelial carcinomas and any other tumors with FGFR fusion or activating mutation or amplification. Up to approximately 185 patients will be enrolled in the phase 1 expansion; and (3) Phase 2 study to confirm ORR of TAS-120 in intra-hepatic CCA patients with tumors harboring FGFR2 gene fusions. Approx. 100 patients will be enrolled in phase 2.

Detailed Description

      Phase 1 Dose Escalation Phase 1 Dose Escalation has been completed as of Dec 2017

      Phase 1 Dose Expansion:

      Up to approximately 185 patients will be enrolled among the 8 groups as outlined below:

        -  Group 1- CCA (iCCA or eCCA) with FGFR2 gene fusions.

        -  Group 2- CCA (iCCA or eCCA) with FGFR2 gene fusions that are chemotherapy naive or
           intolerant to first line chemotherapy (i.e., on chemotherapy regimen ≤ 1 cycle).

        -  Group 3 - CCA (iCCA or eCCA) with FGFR2 gene fusions treated with prior FGFR inhibitors.

        -  Group 4 - CCA (iCCA or eCCA) with other FGFR2 abnormalities, ie, gene mutations,
           rearrangements or amplifications.

        -  Group 5 - GBM or grade III glioma (i.e, anaplastic astrocytoma or anaplastic
           oliogodendroglioma) with FGFR gene fusions or activating mutations

        -  Group 6 - Advanced urothelial carcinoma with FGFR3 fusions or FGFR3 activating
           mutations.

        -  Group 7: Basket of tumor types with tumors harboring FGFR2 amplification (≥10 copies).

        -  Group 8 - Basket of tumor types (except CCA, brain tumors and advanced urothelial
           carcinomas) with tumors harboring FGFR gene fusions or activating mutations.

      Phase 2:

      Approximately 100 iCCA patients with confirmed FGFR2 gene fusions will be treated. Patients
      will be centrally screened for FGFR2 gene fusions. This is a Single arm study with the
      primary endpoint of ORR.
    

Trial Arms

NameTypeDescriptionInterventions
TAS-120ExperimentalTAS-120 tablets, oral; 21-day cycle Dose escalation portion of the study was completed. Dose expansion- patients with tumors harboring specific FGFR aberrations, specifically in CCA, Brain Tumor , Urotherial carcinoma and any other tumors with FGFR fusion, activating mutation and amplification. Phase 2- intra-hepatic CCA patients with tumors harboring FGFR2 gene fusions
  • TAS-120

Eligibility Criteria

        Inclusion Criteria:

        Has histologically or cytologically confirmed, locally advanced, metastatic cancer meeting
        the following criteria:

        Phase 1 Expansion

          1. Patient has failed all standard therapies or standard therapy does not exist or is not
             tolerated.

          2. Patient has specific FGF/FGFR aberrations

               -  Intrahepatic or extrahepatic cholangiocarcinoma with FGFR2 gene fusions or other
                  FGFR2 abnormalities, i.e., gene mutations (see Appendix A), rearrangements or
                  amplifications

               -  Glioblastoma or grade III glioma (i.e., anaplastic astrocytoma or anaplastic
                  oligodendroglioma) with FGFR gene fusions or activating mutations.

               -  Advanced urothelial carcinoma with FGFR3 fusions or FGFR3 activating mutations

               -  All other tumor types harboring FGF9, FGF19 or FGFR2 amplifications (≥ 10
                  copies), FGFR gene fusions, or FGFR activating mutations

        Phase 2

          1. Patient has histologically or cytologically confirmed, locally advanced, metastatic,
             unresectable iCCA harboring FGFR2 gene fusions based on results from a NGS assay by
             the Sponsor's designated central laboratory

          2. Patient has been treated with and failed at least one prior systemic gemcitabine and
             platinum-based chemotherapy for the advanced disease

          3. Must have documentation of radiographic progression of disease on prior systemic
             therapy

          4. Patient has measurable disease as defined by Response Evaluation Criteria in Solid
             Tumors (RECIST) guidelines (version 1.1, 2009) for advanced solid tumors or RANO
             criteria (2010) for brain tumors.

          5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          6. Adequate organ function

        Exclusion Criteria:

        A patient will be excluded from this study if any of the following criteria are met:

          1. History and/or current evidence of non-tumor related alteration of calcium-phosphorus
             homeostasis.

          2. History and/or current evidence of clinically significant ectopic
             mineralization/calcification.

          3. History and/or current evidence of clinically significant retinal disorder confirmed
             by retinal examination.

          4. A serious illness or medical condition(s)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1 - Overall Response Rate (ORR)
Time Frame:12 months
Safety Issue:
Description:Response assessments will be made based on RECIST guidelines (version 1.1, 2009) for solid tumors

Secondary Outcome Measures

Measure:Duration of Response (DOR)
Time Frame:12 months
Safety Issue:
Description:DOR is defined as time from first documentation of response to the first documentation of objective tumor progression or death due to any cause, whichever occurs first
Measure:Disease Control Rate (DCR)
Time Frame:12 months
Safety Issue:
Description:DCR is defined as proportion of patients with objective evidence of complete response, partial response or stable disease
Measure:Progression free survival (PFS)
Time Frame:12 months
Safety Issue:
Description:PFS is defined as time from the day of first dose to the date of first objectively documented disease progression or death
Measure:Patient Reported Outcome (PRO)
Time Frame:12 months
Safety Issue:
Description:PCR is define as the analysis of EQ-5D and EORTC QLQ-C30 from baseline through end of treatment
Measure:Overall Survival (OS)
Time Frame:12 months
Safety Issue:
Description:OS is defined as date of first dose to death date in the safety population of Phase 1 and safety and efficacy population for phase 2

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Taiho Oncology, Inc.

Trial Keywords

  • Breast Cancer
  • Non Small Cell Lung Cancer
  • Gastric Cancer
  • FGF
  • FGFR
  • FGFR abnormality
  • TAS-120
  • Dose Escalation

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