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

• ClinicalTrials.gov Identifier: NCT02052778
• Recruitment Status: Completed
• First Posted: February 3, 2014
• Results First Posted: March 20, 2024
• Last Update Posted: March 20, 2024
• Sponsor: Taiho Oncology, Inc.
• Information provided by (Responsible Party): Taiho Oncology, Inc.

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Cholangiocarcinoma; Urothelial Cancer; Advanced and Metastatic Cancer Patients With Tumors Harboring FGF/FGFR Tumors; Primary CNS Tumors; Breast Cancer; Gastric Cancer	Drug: Futibatinib	Phase 1; Phase 2

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Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 407 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1/2 Study of TAS-120 in Patients With Advanced Solid Tumors Harboring FGF/FGFR Aberrations
• Actual Study Start Date: July 21, 2014
• Actual Primary Completion Date: October 1, 2020
• Actual Study Completion Date: May 29, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Phase 1: Dose Escalation: QOD Dosing: 8 mg; Participants with or without fibroblast growth factor [FGF]/fibroblast growth factor receptor [FGFR] gene abnormalities received orally TAS-120 8 milligrams (mg) orally every other day (QOD; Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Name: TAS-120
Experimental: Phase 1: Dose Escalation: QOD Dosing: 16 mg; Participants with or without FGF/FGFR gene abnormalities received orally TAS-120 16 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Name: TAS-120
Experimental: Phase 1: Dose Escalation: QOD Dosing: 24 mg; Participants with or without FGF/FGFR gene abnormalities received orally TAS-120 24 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Name: TAS-120
Experimental: Phase 1: Dose Escalation: QOD Dosing: 36 mg; Participants with or without FGF/FGFR gene abnormalities received orally TAS-120 36 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Name: TAS-120
Experimental: Phase 1: Dose Escalation: QOD Dosing: 56 mg; Participants with FGF/FGFR gene abnormalities received orally TAS-120 56 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Name: TAS-120
Experimental: Phase 1: Dose Escalation: QOD Dosing: 80 mg; Participants with FGF/FGFR gene abnormalities received orally TAS-120 80 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Name: TAS-120
Experimental: Phase 1: Dose Escalation: QOD Dosing: 120 mg; Participants with FGF/FGFR gene abnormalities received orally TAS-120 120 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Name: TAS-120
Experimental: Phase 1: Dose Escalation: QOD Dosing: 160 mg; Participants with FGF/FGFR gene abnormalities received orally TAS-120 160 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Name: TAS-120
Experimental: Phase 1: Dose Escalation: QOD Dosing: 200 mg; Participants with FGF/FGFR gene abnormalities received orally TAS-120 200 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Name: TAS-120
Experimental: Phase 1: Dose Escalation: QD Dosing: 4 mg; Participants with or without FGF/FGFR gene abnormalities received a dose between 4 mg orally once daily (QD) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Name: TAS-120
Experimental: Phase 1: Dose Escalation: QD Dosing: 8 mg; Participants with or without FGF/FGFR gene abnormalities received a dose between 8 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Name: TAS-120
Experimental: Phase 1: Dose Escalation: QD Dosing: 16 mg; Participants with or without FGF/FGFR gene abnormalities received a dose between 16 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Name: TAS-120
Experimental: Phase 1: Dose Escalation: QD Dosing: 20 mg; Participants with or without FGF/FGFR gene abnormalities received a dose between 20 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Name: TAS-120
Experimental: Phase 1: Dose Escalation: QD Dosing: 24 mg; Participants with or without FGF/FGFR gene abnormalities received a dose between 24 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Name: TAS-120
Experimental: Phase 1: Dose Expansion Cohort 1; Participants with intra-hepatic or extrahepatic cholangiocarcinoma (iCCA or eCCA) harboring FGFR2 gene fusions or rearrangements and who were treated or not treated with prior FGFR inhibitors received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Name: TAS-120
Experimental: Phase 1: Dose Expansion: Cohort 2; Participants with primary central nervous system (CNS) tumors harboring FGFR gene fusions or FGFR1 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Name: TAS-120
Experimental: Phase 1: Dose Expansion: Cohort 3; Participants with advanced urothelial carcinoma harboring FGFR3 gene fusions or FGFR3 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Name: TAS-120
Experimental: Phase 1: Dose Expansion: Cohort 4; Participants with breast or gastric cancer with harboring FGFR2 amplification received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Name: TAS-120
Experimental: Phase 1:Dose Expansion: Cohort 5; Participants with tumor types harboring FGFR gene fusions or activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Name: TAS-120
Experimental: Phase 1: Dose Expansion: Cohort 6; Participants who were not included in Cohorts 1 to 5 received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Name: TAS-120
Experimental: Phase 1: Dose Expansion: Sub-cohort 1; Participants with iCCA who were enrolled prior to the confirmation of the recommended Phase 2 dose (RP2D) received TAS-120 16 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Name: TAS-120
Experimental: Phase 1: Dose Expansion: Sub-cohort 2; Participants with other tumor types who were enrolled prior to the confirmation of the RP2D received TAS-120 16 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Name: TAS-120
Experimental: Phase 2; Participants with iCCA with tumors harboring FGFR2 gene rearrangements received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Name: TAS-120

Outcome Measures

Primary Outcome Measures :

1. Phase 1: Dose Escalation-Maximum Tolerated Dose (MTD) [ Time Frame: Cycle 1 (21-day cycle) ]
   MTD:Highest dose level at which <33% of participants experience dose-limiting toxicity (DLT) during Cycle1. DLT: >=Grade(G)3: - nonhematologic toxicity, - nausea/vomiting lasting >48hrs(uncontrolled by aggressive antiemetic), - diarrhea lasting >48hrs (unresponsive to antidiarrheal drug); G4 neutropenia lasting >7days; Febrile neutropenia (ANC<1000/mm^3 with body temperature=>38.3°C/sustained temperature >=38°C for >1hr; Thrombocytopenia G4/G3 with bleeding, required blood transfusion; Corneal disorder worsened by 1 grade or more; Increased phosphorus: >=9mg/dL or >=7mg/dL lasting for >=7days or phosphate lowering therapy[PLT] for 7days); Creatinine increase (>1.5×upper limit of normal [ULN]) lasting for >=7 days associated with serum phosphorus >5.5 mg/dL(PLT=7days)/calcium×phosphorus >55 mg/dL(PLT=7days); Hypercalcemia G2 for >7days or G3; Ectopic de novo calcification in soft tissues; >G2 DLT: prevented Cycle 1 completion, inability to start Cycle 2 within 2 weeks of schedule.
2. Phase 1: Dose Escalation-Recommended Phase 2 Dose (RP2D) of TAS-120 [ Time Frame: Cycle 1 (21-day cycle) ]
   RP2D was MTD or less. MTD: Highest dose level at which <33% of participants experience DLT) during Cycle1. DLT: >=Grade(G)3: - nonhematologic toxicity, - nausea/vomiting lasting >48hrs(uncontrolled by aggressive antiemetic), - diarrhea lasting >48hrs (unresponsive to antidiarrheal drug); G4 neutropenia lasting >7days; Febrile neutropenia (ANC<1000/mm^3 with body temperature=>38.3°C/sustained temperature >=38°C for >1hr; Thrombocytopenia G4/G3 with bleeding, required blood transfusion; Corneal disorder worsened by 1 grade or more; Increased phosphorus: >=9mg/dL or >=7mg/dL lasting for >=7days or phosphate lowering therapy[PLT] for 7days); Creatinine increase (>1.5×upper limit of normal [ULN]) lasting for >=7 days associated with serum phosphorus >5.5 mg/dL(PLT=7days)/calcium×phosphorus >55 mg/dL(PLT=7days); Hypercalcemia G2 for >7days or G3; Ectopic de novo calcification in soft tissues; >G2 DLT: prevented Cycle 1 completion, inability to start Cycle 2 within 2 weeks of schedule.
3. Phase 1: Dose Expansion: Percentage of Participants With Objective Response [ Time Frame: 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 ]
   Objective response was defined as proportion of participants who had achieved best overall response of partial response (PR) or complete response (CR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The CR was defined as a disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must had reduction in short axis to <10 millimeters (mm) and PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions. For Cohorts 1 to 6: Objective response was based on Independent Review Committee (IRC) and for pooled Sub-cohort: Objective response was based on investigator review.
4. Phase 2: Percentage of Participants With Objective Response [ Time Frame: Up to approximately 37.5 months (through cut-off date 29-May-2021) ]
   Objective response was defined as proportion of participants who had achieved best overall response of PR or CR per RECIST v1.1. CR was defined as a disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must had reduction in short axis to <10 mm and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. The Phase 2 evaluation of objective response was based on central independent CT/MRI image assessment.

Secondary Outcome Measures :

1. Phase 1: Dose Expansion: Duration of Response (DOR) [ Time Frame: 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 ]
   A DOR was defined as the time (in months) from the first documentation of response (CR or PR) to the first documentation of objective progressive disease (PD) or death due to any cause, whichever occurred first. Participants who started subsequent anticancer therapy without a prior reported progression were censored at the last tumor assessments prior to initiation of the subsequent anticancer therapy. For Cohorts 1 to 6: DOR was based on IRC and for Group 3, 4, 5, 6 and for pooled Sub-cohort: DOR was based on investigator review.
2. Phase 2: Duration of Response (DOR) [ Time Frame: Up to approximately 37.5 months (through cut-off date 29-May-2021) ]
   A DOR was defined as the time (in months) from the first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurred first. Participants who started subsequent anticancer therapy without a prior reported progression were censored at the last tumor assessments prior to initiation of the subsequent anticancer therapy. Kaplan-Meier method was used for the analysis.
3. Phase 1: Dose Expansion: Disease Control Rate (DCR) [ Time Frame: 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 ]
   A DCR was defined as the proportion of participants with objective evidence of CR, PR, or stable disease (SD), except that there was no requirement for a confirmation of an SD, if it is maintained for at least 6 weeks post treatment initiation. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes might had reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the Baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taken as a reference the smallest sum diameters while on study. For Cohorts 1 to 6: DCR was based on IRC and for pooled Sub-cohort: DCR was based on investigator review.
4. Phase 2: Disease Control Rate (DCR) [ Time Frame: Up to approximately 37.5 months (through cut-off date 29-May-2021) ]
   A DCR was defined as the proportion of participants with objective evidence of CR, PR, or SD, except that there was no requirement for a confirmation of an SD response, if it is maintained for at least 6 weeks post treatment initiation. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes might had reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the Baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taken as a reference the smallest sum diameters while on study. DCR was based on IRC.
5. Phase 1: Dose Expansion: Progression-free Survival (PFS) [ Time Frame: up to approximately 27.5 months (through cut-off date 30-Jun-2019) ]
   A PFS was defined as the time (in months) from the day of the first dose to the date of first documented disease progression or death (due to any cause), whichever occurred first. Participants who died without a reported disease progression were considered to have progressed on the date of their death, participants who did not progress or die were censored on the date of their last tumor assessment, participants who had no on-study assessments and did not die were censored on the first dosing date, and participants who started any subsequent anti-cancer therapy without a prior reported progression were censored at the last tumor assessment prior to initiation of the subsequent anti-cancer therapy. PFS assessment per protocol was by IRC assessment for Cohorts 1 to 6 and for pooled Sub-cohort: PFS was based on investigator review.
6. Phase 2: Progression-free Survival (PFS) [ Time Frame: Up to approximately 37.5 months (through cut-off date 29-May-2021) ]
   A PFS was defined as the time (in months) from the day of the first dose to the date of first objectively documented disease progression or death (any cause), whichever occurred first. Participants who had died without a reported disease progression were considered to have progressed on the date of their death, participants who did not progress or die were censored on the date of their last tumor assessment, participants who had no on-study assessments and did not die were censored on the first dosing date, and participants who started any subsequent anti-cancer therapy without a prior reported progression were censored at the last tumor assessment prior to initiation of the subsequent anti-cancer therapy. PFS was analyzed as using Kaplan-Meier estimate.
7. Phase 1: Dose Expansion: Overall Survival (OS) [ Time Frame: up to approximately 27.5 months (through cut-off date 30-Jun-2019) ]
   An OS was defined as the time (in months) from the date of the first dose to the death date. In the absence of death confirmation or for participants alive as of the OS cut-off date, survival time was censored at the date of last study follow-up, or the cut-off date, whichever was earlier.
8. Phase 2: Overall Survival (OS) [ Time Frame: Up to approximately 37.5 months (through cut-off date 29-May-2021) ]
   An OS was defined as the time (in months) from the date of the first dose to the death date. In the absence of death confirmation or for participants alive as of the OS cut-off date, survival time was censored at the date of last study follow-up, or the cut-off date, whichever was earlier.
9. Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits [ Time Frame: 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]) ]
   EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of participants who chose each category.
10. Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits [ Time Frame: 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]) ]
    EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of participants who chose each category.
11. Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits [ Time Frame: 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]) ]
    EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of participants who chose each category.
12. Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits [ Time Frame: 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]) ]
    EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of participants who chose each category.
13. Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits [ Time Frame: 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]) ]
    EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of participants who chose each category.
14. Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits [ Time Frame: 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]) ]
    EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. A vertical VAS allows the participants to indicate their health state that day, and ranged from 0 (worst imaginable) to 100 (best imaginable), with higher scores indicating better health state.
15. 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 [ Time Frame: 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]) ]
    EORTC QLQ-C30 is a cancer-specific instrument that contains 30 questions for evaluation of new chemotherapy & assessment of participant reported outcome. EORTC QLQ-C30 included global health status/quality of life (GHS/QOL), functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, nausea/vomiting), and 6 single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Most questions from QLQ-C30 are 4-point scale (1/Not at All to 4/Very Much), except Items 29-30, which comprise GHS scale & are 7-point scale (1/Very Poor to 7/Excellent). GHS total score is calculated as ([{Q29+Q30}/2]-1)/6*100. Answers are converted into grading scale, with values between 0 (worse outcome) to100 (best outcome). High score represents a favorable outcome with best quality of life for participant.
16. Phase 1: Dose Expansion: Number of Participants With Any Adverse Events (AEs) and Any Serious AEs (SAEs) [ Time Frame: From the first dose up to approximately 50.5 months (through cut-off date 29-May-2021) ]
    An AE was defined as any untoward medical condition that occurred in a participant from the time the informed consent form (ICF) was signed and does not necessarily had a causal relationship with the use of the product. An SAE was an AE that falls into one or more of the following categories: a. resulted in death, b. was life threatening, c. required inpatient hospitalization or prolongation of existing hospitalization, d. resulted in persistent or significant disability or incapacity, e. was a congenital anomaly/birth defect, f. other important medical event.
17. Phase 2: Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) [ Time Frame: From the first dose up to approximately 37.5 months (through cut-off date 29-May-2021) ]
    An AE was defined as any untoward medical condition that occurs in a participant from the time the informed consent form (ICF) was signed and does not necessarily had a causal relationship with the use of the product. An SAE was an AE that falls into one or more of the following categories: a. resulted in death, b. was life threatening, c. required inpatient hospitalization or prolongation of existing hospitalization, d. resulted in persistent or significant disability or incapacity, e. was a congenital anomaly/birth defect, f. other important medical event.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Arizona

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States, 85234

Mayo Clinic (AZ)

Scottsdale, Arizona, United States, 85259

The University of Arizona Cancer Center - North Campus

Tucson, Arizona, United States, 85719

United States, California

City of Hope National Medical Center

Duarte, California, United States, 91010

UCSF Helen Diller Family Comprehensive Cancer Center. Mission Bay

San Francisco, California, United States, 94158

United States, Georgia

Cancer Treatment Centers of America

Newnan, Georgia, United States, 30265

United States, Illinois

Cancer Treatment Centers of America Zion, IL

Zion, Illinois, United States, 60099

United States, Kansas

The University of Kansas Cancer Center

Fairway, Kansas, United States, 66205

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Dana Farber Cancer Institution

Boston, Massachusetts, United States, 02215

United States, Michigan

Wayne State Universtity (Karmanos Cancer Institute)

Detroit, Michigan, United States, 48201

United States, Minnesota

Mayo Clinic (MN)

Rochester, Minnesota, United States, 55905

United States, New Mexico

New Mexico Cancer Care Alliancer

Albuquerque, New Mexico, United States, 87106

United States, New York

Roswell Park Cancer Institute

Buffalo, New York, United States, 14263

United States, Pennsylvania

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Sidney Kimmel Cancer Center at Jefferson

Philadelphia, Pennsylvania, United States, 19107

University of Pittsburgh Medical Center Hillman Cancer Center

Pittsburgh, Pennsylvania, United States, 15232

United States, South Carolina

Greenville Health System ITOR,Clinical Research Unit

Greenville, South Carolina, United States, 29605

Spartanburg Medical Center

Spartanburg, South Carolina, United States, 29303

United States, Texas

Mary Crowley Cancer Research - Medical City

Dallas, Texas, United States, 75230

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

United States, Utah

University of Utah, Huntsman Cancer Hospital

Salt Lake City, Utah, United States, 84112

United States, Virginia

University of Virginia Cancer Center

Charlottesville, Virginia, United States, 22903

United States, Washington

Virginia Mason Cancer Center

Seattle, Washington, United States, 98101

United States, Wisconsin

University of Wisconsin Clinical Science Center

Madison, Wisconsin, United States, 53792

Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Australia

Royal Melbourne Hospital

Melbourne, Australia

Canada

Sunnybrook Research Institue

Toronto, Canada, M4N3M5

France

Centre Léon Bérard Bât

Lyon, Cedex, France, 69373

Institut Bergonie

Bordeaux, France, 33076

Hospices Civils de Lyon

Bron, France, 69677

Pitié-Salpêtrière Hospital

Paris, France, 75013

Rennes, Centre Eugène Marquis

Rennes cedex, France, 35042

Institute Goustave-Roussy-DITEP

Villejuif, France, 94805

Germany

University Hospital Essen, West German Cancer Center, Department of Medical Oncology

Essen, Germany, 45147

Hong Kong

The Chinese University of Hong Kong

Sha Tin, Hong Kong

Italy

Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

Milano, Italy, 20133

UOC Oncologia Medica 1 I"V - Istituto Oncologico Veneto - IRCCS

Padova, Italy, 35128

Japan

Hokkaido University Hospital

Hokkaido, Japan, 060-8648

Kyoto University Hospital, Department of Clinical Pharmacology and Therapeutics

Kyoto, Japan, 606-8507

Tohoku University Hospital

Miyagi, Japan, 980-8574

Osaka International Cancer Institute

Osaka, Japan, 541-8567

National Cancer Center Hospital

Tokyo, Japan, 104-0045

Korea, Republic of

Yonsei University, Severance Hospital (Seoul)

Seoul, Korea, Republic of, 03722

ASAN Medical Center (Seoul)

Seoul, Korea, Republic of, 05505

Samsung Medical Center (Seoul)

Seoul, Korea, Republic of, 06351

Seoul National University Hospital

Seoul, Korea, Republic of, 110-744

Netherlands

University Hospital Jenna

Jenna, Netherlands, 07740

Spain

Val D'Hebron University Hospital

Barcelona, Spain, 08035

Hospital Clinic i Provincial de Barcelona,

Barcelona, Spain, 08036

University Hospital Ramón y Cajal

Madrid, Spain, 28034

Centro Integral Oncológico Clara Campal - Hospital Universitario Madrid Sanchinarro

Madrid, Spain

Taiwan

Cheng Kung University Hospital

Tainan, Taiwan, 704

National Taiwan University Hospital

Taipei, Taiwan, 10048

United Kingdom

Guy's and St Thomas' NHS Foundation Trust

London, United Kingdom, SE1 9RT

Sarah Cannon Research Institute

London, United Kingdom, W1G 6AD

University College London Hospital

London, United Kingdom, W1T 7HA

The Christie NHS Foundation Trust

Manchester, United Kingdom, M20 4BX

Sponsors and Collaborators

Taiho Oncology, Inc.

  Study Documents (Full-Text)

Documents provided by Taiho Oncology, Inc.:

Study Protocol  [PDF] August 1, 2019

Statistical Analysis Plan  [PDF] October 15, 2020

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Taiho Oncology, Inc.
• ClinicalTrials.gov Identifier: NCT02052778
• Other Study ID Numbers: TPU-TAS-120-101; 2013-004810-16 ( EudraCT Number )
• First Posted: February 3, 2014
• Results First Posted: March 20, 2024
• Last Update Posted: March 20, 2024
• Last Verified: February 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Taiho Oncology, Inc.:

FGF; FGFR; Futibatinib; TAS-120

Additional relevant MeSH terms:

Neoplasms; Cholangiocarcinoma; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Futibatinib; Antineoplastic Agents