Phase 1/2 Study of TAS-120 in Patients With Advanced Solid Tumors Harboring FGF/FGFR Aberrations


Condition: Cholangiocarcinoma, Brain Tumor, Urothelial Cancer, Other Tumor Types With FGFR2 Gene Fusions, Activating Mutations, FGFR2 Amplification

Intervention:

  • Drug: TAS-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.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02052778

Sponsor: Taiho Oncology, Inc.

Primary Outcome Measures:

  • Measure: Phase 1 – Overall Response Rate (ORR)
  • Time Frame: 12 months
  • Safety Issue:
  • Measure: Phase 1 – Early Progression Rate (EPR) for GBM or grade III glioma
  • Time Frame: 12 months
  • Safety Issue:
  • Measure: Phase 2 – Overall Response Rate (ORR)
  • Time Frame: 12 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Duration of Response (DOR)
  • Time Frame: 12 months
  • Safety Issue:
  • Measure: Disease Control Rate (DCR)
  • Time Frame: 12 months
  • Safety Issue:
  • Measure: Progression free survival (PFS)
  • Time Frame: 12 months
  • Safety Issue:
  • Measure: Patient Reported Outcome (PRO)
  • Time Frame: 12 months
  • Safety Issue:
  • Measure: Overall Survival (OS)
  • Time Frame: 12 months
  • Safety Issue:

Estimated Enrollment: 371

Study Start Date: July 2014

Phase: Phase 1/Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

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:

  1. A patient will be excluded from this study if any of the following criteria are met:
  2. History and/or current evidence of non-tumor related alteration of calcium-phosphorus homeostasis.
  3. History and/or current evidence of clinically significant ectopic mineralization/calcification.
  4. History and/or current evidence of clinically significant retinal disorder confirmed by retinal examination.
  5. A serious illness or medical condition(s)

Contact:

  • Jerry Huang, MD

Locations:

  • Banner MD Anderson Cancer Center
  • Gilbert Arizona 85234 United States
  • Mayo Clinic (AZ)
  • Scottsdale Arizona 85259 United States
  • City of Hope National Medical Center
  • Duarte California 91010 United States
  • UCSF – Helen Diller
  • San Francisco California 94158 United States
  • Mayo Clinic (Jacksonville)
  • Jacksonville Florida 32224 United States
  • Florida Hospital
  • Orlando Florida 32804 United States
  • Cancer Treatment Centers of America
  • Newnan Georgia 30265 United States
  • Cancer Treatment Centers of America Zion, IL
  • Zion Illinois 60099 United States
  • The University of Kansas Cancer Center
  • Westwood Kansas 66205 United States
  • Massachusetts General Hospital
  • Boston Massachusetts 02114 United States
  • Cancer Center at Beth Israel Deaconess Medical Center
  • Boston Massachusetts 02215 United States
  • Dana Farber Cancer Institution
  • Boston Massachusetts 02215 United States
  • Wayne State Universtity (Karmanos Cancer Institute)
  • Detroit Michigan 48201 United States
  • Mayo Clinic (MN)
  • Rochester Minnesota 55905 United States
  • New Mexico Cancer Care Alliance
  • Albuquerque New Mexico 87106 United States
  • Roswell Park Cancer Institute
  • Buffalo New York 14263 United States
  • University of Pennsylvania
  • Philadelphia Pennsylvania 19104 United States
  • Sidney Kimmel Cancer Center at Jefferson
  • Philadelphia Pennsylvania 19107 United States
  • Cancer Treatment Centers of America Philadelphia, PA
  • Philadelphia Pennsylvania 19124 United States
  • University of Pittsburgh Medical Center
  • Pittsburgh Pennsylvania 15232 United States
  • Greenville Health System ITOR
  • Greenville South Carolina 29605 United States
  • Spartanburg Medical Center
  • Spartanburg South Carolina 29303 United States
  • Mary Crowley
  • Dallas Texas 75251 United States
  • MD Anderson Cancer Center
  • Houston Texas 77030 United States
  • Virginia Mason Cancer Center
  • Seattle Washington 98101 United States
  • UW Carbone Cancer Center
  • Madison Wisconsin 53792 United States
  • Medical College of Wisconsin
  • Milwaukee Wisconsin 53226 United States
  • Royal Melbourne Hospital
  • Melbourne Australia
  • Scientia Clinical Research University of New South Wales
  • Randwick 2031 Australia
  • Scientia Clinical Research University of New South Wales
  • Randwick NSW 2031 Australia
  • Institut Bergonie
  • Bordeaux 33000 France
  • Hospices Civils de Lyon
  • Bron 69677 France
  • Centre Léon Bérard Bât
  • Lyon 69008 France
  • Pitié-Salpêtrière Hospital
  • Paris 75013 France
  • Institute Goustave-Roussy
  • Paris France
  • Rennes, Centre Eugène Marquis
  • Rennes cedex 35042 France
  • The Chinese University of Hong Kong
  • Sha Tin Hong Kong
  • Prince of Wales Hospital
  • Shatin Hong Kong
  • Nagoya University Hospital
  • Nagoya 466-8560 Japan
  • Osaka International Cancer Institute
  • Osaka 541-8567 Japan
  • Yonsei University, Severance Hospital (Seoul)
  • Seoul 03722 Korea, Republic of
  • ASAN Medical Center (Seoul)
  • Seoul 05505 Korea, Republic of
  • Samsung Medical Center (Seoul)
  • Seoul 06351 Korea, Republic of
  • Seoul National University Hospital
  • Seoul 110-744 Korea, Republic of
  • University of Amsterdam
  • Amsterdam 1105AZ Netherlands
  • Val D’Hebron University Hospital
  • Barcelona 08035 Spain
  • Hospital Clinic i Provincial de Barcelona,
  • Barcelona 08036 Spain
  • University Hospital Ramón y Cajal
  • Madrid 28034 Spain
  • Centro Integral Oncológico Clara Campal – Hospital Universitario Madrid Sanchinarro
  • Madrid Spain
  • National Taiwan University Hospital
  • Taipei 10048 Taiwan
  • Guy’s and St Thomas’ NHS Foundation Trust
  • London SE1 9RT United Kingdom
  • University College London Hospital
  • London W1T 7HA United Kingdom
  • Sarah Cannon Research Institute
  • London United Kingdom

View trial on ClinicalTrials.gov


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