Clinical trial NCT02052778: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cholangiocarcinoma
Urothelial Cancer
Advanced and Metastatic Cancer Patients With Tumors Harboring FGF/FGFR Tumors
Primary CNS Tumors
Breast Cancer
Gastric Cancer
Keywords: FGF
FGFR
Futibatinib
TAS-120
Lead sponsor: Taiho Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2014-02-03
Enrollment: 407
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is an open-label, nonrandomized, Phase 1/2 study for the fibroblast growth factor receptor (FGFR) inhibitor futibatinib (TAS-120). The purpose of the study is to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic, and anti-tumor activity of futibatinib in patients with advanced solid tumors with and without genomic FGF/FGFR abnormalities. The study will be conducted in 3 parts:

1. Dose escalation portion to determine the -Maximum Tolerated Dose and/ or Recommended Phase 2 Dose of futibatinib.
2. Phase 1 expansion portion to further evaluate the safety and efficacy of futibatinib in patients with tumors harboring FGF/FGFR aberrations, including patients with cholangiocarcinoma (CCA), primary central nervous system tumors, urothelial carcinoma, breast cancer, gastric cancer.
3. Phase 2 study portion to confirm objective response rate of futibatinib in intrahepatic CCA patients with tumors harboring FGFR2 gene rearrangements (incl fusions).


Eligibility criteria: Inclusion Criteria:

1. Provide written informed consent
2. Age ≥ 18 years of age
3. Has histologically or cytologically confirmed, locally advanced or metastatic cancer
4. The following specific criteria for each study portion

   Phase 1 (Dose Escalation):
   * Patients with any type of solid tumor
   * Disease progression following standard therapies or intolerant to prior standard therapies

   Phase 1 (Dose Expansion)
   * Have at least one FGF/FGFR aberration
   * Disease progression following standard therapies or were intolerant to prior standard therapies (including prior FGFR inhibitors).
   * Have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009) for advanced solid tumors or Response Assessment in Neuro-Oncology criteria (2010) for brain tumors.
   * Patients with any of the following tumor types

     * Patients with intrahepatic or extrahepatic CCA harboring FGFR2 gene fusions or other FGFR2 aberrations
     * Patients with primary CNS tumors
     * Patients with advanced urothelial carcinoma with FGFR3 fusions or FGFR3 activating mutations
     * Patients with breast cancer or gastric cancer
     * Patients with other solid tumor types harboring FGFR gene fusions or activating mutations
     * Patients with solid tumor types and other FGF/FGFR alterations not listed above

   Phase 2
   * Patients with iCCA and FGFR2 gene rearrangements (incl fusions)
   * Have been treated with at least one prior systemic gemcitabine and platinum-based chemotherapy
   * Must have documentation of radiographic progression of disease
   * No prior FGFR inhibitor
   * Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009)
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
6. Adequate organ function.

Exclusion Criteria:

1. History and/or current evidence of clinically significant 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
4. A serious illness or medical condition(s)
5. Pregnant or breast-feeding female

Primary outcomes:
measure: Phase 1: Dose Escalation-Maximum Tolerated Dose (MTD)
timeFrame: Cycle 1 (21-day cycle)
measure: Phase 1: Dose Escalation-Recommended Phase 2 Dose (RP2D) of TAS-120
timeFrame: Cycle 1 (21-day cycle)
measure: Phase 1: Dose Expansion: Percentage of Participants With Objective Response
timeFrame: Up to approximately 50.5 months (through cut-off date 29-May-2021) for Cohorts 1 to 6; up to approximately 27.5 months (through cut-off date 30-Jun-2019) for pooled sub-cohorts
measure: Phase 2: Percentage of Participants With Objective Response
timeFrame: Up to approximately 37.5 months (through cut-off date 29-May-2021)
Secondary outcomes:
measure: Phase 1: Dose Expansion: Duration of Response (DOR)
timeFrame: Up to approximately 50.5 months (through cut-off date 29-May-2021) for Cohorts 1 to 6; up to approximately 27.5 months (through cut-off date 30-Jun-2019) for pooled sub-cohorts
measure: Phase 2: Duration of Response (DOR)
timeFrame: Up to approximately 37.5 months (through cut-off date 29-May-2021)
measure: Phase 1: Dose Expansion: Disease Control Rate (DCR)
timeFrame: Up to approximately 50.5 months (through cut-off date 29-May-2021) for Cohorts 1 to 6; up to approximately 27.5 months (through cut-off date 30-Jun-2019) for pooled sub-cohort
measure: Phase 2: Disease Control Rate (DCR)
timeFrame: Up to approximately 37.5 months (through cut-off date 29-May-2021)
measure: Phase 1: Dose Expansion: Progression-free Survival (PFS)
timeFrame: up to approximately 27.5 months (through cut-off date 30-Jun-2019)
measure: Phase 2: Progression-free Survival (PFS)
timeFrame: Up to approximately 37.5 months (through cut-off date 29-May-2021)
measure: Phase 1: Dose Expansion: Overall Survival (OS)
timeFrame: up to approximately 27.5 months (through cut-off date 30-Jun-2019)
measure: Phase 2: Overall Survival (OS)
timeFrame: Up to approximately 37.5 months (through cut-off date 29-May-2021)
measure: Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits
timeFrame: Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months])
measure: Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits
timeFrame: Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months])
measure: Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits
timeFrame: Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months])
measure: Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits
timeFrame: Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months])
measure: Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits
timeFrame: Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months])
measure: Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits
timeFrame: Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months])
measure: Phase 2:Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score at Specified Timepoints
timeFrame: Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months])
measure: Phase 1: Dose Expansion: Number of Participants With Any Adverse Events (AEs) and Any Serious AEs (SAEs)
timeFrame: From the first dose up to approximately 50.5 months (through cut-off date 29-May-2021)
measure: Phase 2: Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs)
timeFrame: From the first dose up to approximately 37.5 months (through cut-off date 29-May-2021)
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic (AZ)
state: Arizona
city: Tucson
country: United States
facility: The University of Arizona Cancer Center - North Campus
state: Arizona
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center. Mission Bay
state: California
city: Newnan
country: United States
facility: Cancer Treatment Centers of America
state: Georgia
city: Zion
country: United States
facility: Cancer Treatment Centers of America Zion, IL
state: Illinois
city: Fairway
country: United States
facility: The University of Kansas Cancer Center
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institution
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State Universtity (Karmanos Cancer Institute)
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic (MN)
state: Minnesota
city: Albuquerque
country: United States
facility: New Mexico Cancer Care Alliancer
state: New Mexico
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Sidney Kimmel Cancer Center at Jefferson
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center Hillman Cancer Center
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville Health System ITOR,Clinical Research Unit
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Medical Center
state: South Carolina
city: Dallas
country: United States
facility: Mary Crowley Cancer Research - Medical City
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah, Huntsman Cancer Hospital
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Cancer Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Clinical Science Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
city: Toronto
country: Canada
facility: Sunnybrook Research Institue
city: Lyon
country: France
facility: Centre Léon Bérard Bât
state: Cedex
city: Bordeaux
country: France
facility: Institut Bergonie
city: Bron
country: France
facility: Hospices Civils de Lyon
city: Paris
country: France
facility: Pitié-Salpêtrière Hospital
city: Rennes cedex
country: France
facility: Rennes, Centre Eugène Marquis
city: Villejuif
country: France
facility: Institute Goustave-Roussy-DITEP
city: Essen
country: Germany
facility: University Hospital Essen, West German Cancer Center, Department of Medical Oncology
city: Sha Tin
country: Hong Kong
facility: The Chinese University of Hong Kong
city: Milano
country: Italy
facility: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
city: Padova
country: Italy
facility: UOC Oncologia Medica 1 I"V - Istituto Oncologico Veneto - IRCCS
city: Hokkaido
country: Japan
facility: Hokkaido University Hospital
city: Kyoto
country: Japan
facility: Kyoto University Hospital, Department of Clinical Pharmacology and Therapeutics
city: Miyagi
country: Japan
facility: Tohoku University Hospital
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University, Severance Hospital (Seoul)
city: Seoul
country: Korea, Republic of
facility: ASAN Medical Center (Seoul)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center (Seoul)
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Jenna
country: Netherlands
facility: University Hospital Jenna
city: Barcelona
country: Spain
facility: Val D'Hebron University Hospital
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona,
city: Madrid
country: Spain
facility: University Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Centro Integral Oncológico Clara Campal - Hospital Universitario Madrid Sanchinarro
city: Tainan
country: Taiwan
facility: Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute
city: London
country: United Kingdom
facility: University College London Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
References:
citation: Bahleda R, Meric-Bernstam F, Goyal L, Tran B, He Y, Yamamiya I, Benhadji KA, Matos I, Arkenau HT. Phase I, first-in-human study of futibatinib, a highly selective, irreversible FGFR1-4 inhibitor in patients with advanced solid tumors. Ann Oncol. 2020 Oct;31(10):1405-1412. doi: 10.1016/j.annonc.2020.06.018. Epub 2020 Jul 2.