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An Open-label Phase I Study of Orally Available Novel Small-molecule Fibroblast Growth Factor Receptors (FGFR) 1,2,3 and 4 Inhibitor, ASP5878 at Single and Multiple Doses in Patients With Solid Tumors

This study has been completed.
Sponsor:
Collaborator:
Astellas Pharma Global Development, Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT02038673
First received: January 15, 2014
Last updated: September 12, 2017
Last verified: September 2017
  Purpose
The objectives of this study are to determine the tolerability, safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of oral ASP5878 in patients with solid tumors.

Condition Intervention Phase
Solid Tumors Drug: ASP5878 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Phase I Study of Oral ASP5878 at Single and Multiple Doses in Patients With Solid Tumors

Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Dose-escalation part and Expansion part: Safety assessed by Adverse Events (AEs) [ Time Frame: Up to 18 months ]
    Until one of the discontinuation criteria is met.

  • Dose-escalation part and Expansion part:Safety assessed by Vital signs [ Time Frame: Up to 18 months ]
    Blood pressure, pulse rate and body temperature, Until one of the discontinuation criteria is met.

  • Dose-escalation part and Expansion part:Safety assessed by Body weight [ Time Frame: Up to 18 months ]
    Until one of the discontinuation criteria is met.

  • Dose-escalation part and Expansion part:Safety assessed by Laboratory tests [ Time Frame: Up to 18 months ]
    Hematology, blood biochemistry, blood coagulation tests and urinalysis, until one of the discontinuation criteria is met.

  • Dose-escalation part and Expansion part:Safety assessed by 12-lead ECGs [ Time Frame: Up to 18 months ]
    ECG: Electrocardiogram, until one of the discontinuation criteria is met.

  • Dose-escalation part and Expansion part: Ophthalmology [ Time Frame: Up to 18 months ]
    Eyesight, funduscopy, slit lamp microscopy, and Optical Coherence Tomography, until one of the discontinuation criteria is met.

  • Dose-escalation part and Expansion part: Bone density measurement [ Time Frame: Up to 18 months ]
    Until one of the discontinuation criteria is met.

  • Dose-escalation part and Expansion part: Imaging study [ Time Frame: Up to 18 months ]
    Until one of the discontinuation criteria is met.

  • Expansion part only: Echocardiogram [ Time Frame: Up to 18 months ]
    Until one of the discontinuation criteria is met.


Secondary Outcome Measures:
  • Dose-escalation part: Pharmacokinetics (PK) parameter of ASP5878 in plasma: Cmax [ Time Frame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1 ]
    Cmax: Maximum concentration, Cycle 0: single dose, Cycle 1: multiple dose after Cycle 0

  • Dose-escalation part:PK parameter of ASP5878 in plasma: tmax [ Time Frame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1 ]
    tmax: Time of Cmax

  • Dose-escalation part:PK parameter of ASP5878 in plasma: AUClast [ Time Frame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1 ]
    AUClast: Area under the concentration-time curve from the time of dosing extrapolated to the last measurable concentration

  • Dose-escalation part: PK parameter of ASP5878 in plasma: AUCinf [ Time Frame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1 ]
    AUCinf: Area under the concentration-time curve from the time of dosing extrapolated to time infinity

  • Dose-escalation part: PK parameter of ASP5878 in plasma: t1/2 [ Time Frame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1 ]
    t1/2: Terminal elimination half-life

  • Dose-escalation part: PK parameter of ASP5878 in plasma: CL/F [ Time Frame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1 ]
    CL/F: Apparent total systemic clearance

  • Dose-escalation part: PK parameter of ASP5878 in plasma: Vz/F [ Time Frame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1 ]
    Vz/F: Apparent volume of distribution during the terminal elimination phase

  • Dose-escalation part: PK parameter of ASP5878 in urine: Ae [ Time Frame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1 ]
    Ae: Amount of ASP5878 excreted into the urine

  • Dose-escalation part: PK parameter of ASP5878 in urine: CLR [ Time Frame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1 ]
    CLR: Renal clearance

  • Dose-escalation part: Pharmacodynamic (PD) parameter: Serum FGF23 concentrations [ Time Frame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1 ]
    FGF: Fibroblast Growth Factor

  • Dose-escalation part: PD parameter: Serum inorganic phosphorus concentrations [ Time Frame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1 ]
  • Dose-escalation part: PD parameter: Serum calcium concentrations [ Time Frame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1 ]
  • Dose-escalation part: PD parameter: Serum iPTH concentrations [ Time Frame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1 ]
    iPTH: Intact Parathyroid Hormone

  • Dose-escalation part: PD parameter: Serum calcitriol concentrations [ Time Frame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1 ]
  • Expansion part: PK parameter of ASP5878 in plasma: Cmax [ Time Frame: Day 1 and 5 at Cycle 1 ]
  • Expansion part: PK parameter of ASP5878 in plasma: tmax [ Time Frame: Day 1 and 5 at Cycle 1 ]
  • Expansion part: PK parameter of ASP5878 in plasma: AUClast [ Time Frame: Day 1 and 5 at Cycle 1 ]
  • Expansion part: PK parameter of ASP5878 in plasma: AUCinf [ Time Frame: Day 1 and 5 at Cycle 1 ]
  • Expansion part: PK parameter of ASP5878 in plasma: t1/2 [ Time Frame: Day 1 and 5 at Cycle 1 ]
  • Expansion part: PK parameter of ASP5878 in plasma: CL/F [ Time Frame: Day 1 and 5 at Cycle 1 ]
  • Expansion part: PK parameter of ASP5878 in plasma: Vz/F [ Time Frame: Day 1 and 5 at Cycle 1 ]
  • Expansion part: PD parameter: Serum FGF19 concentrations [ Time Frame: Up to 18 months ]
    Until one of the discontinuation criteria is met.

  • Expansion part: PD parameter: Serum FGF23 concentrations [ Time Frame: Up to 18 months ]
    Until one of the discontinuation criteria is met.

  • Expansion part: PD parameter: Serum inorganic phosphorus concentrations [ Time Frame: Up to 18 months ]
    Until one of the discontinuation criteria is met.

  • Expansion part: PD parameter: Serum iPTH concentrations [ Time Frame: Up to 18 months ]
    Until one of the discontinuation criteria is met.

  • Expansion part: PD parameter: Serum calcitriol concentrations [ Time Frame: Up to 18 months ]
    Until one of the discontinuation criteria is met.

  • Expansion part: Antitumor activity evaluated based on RECIST [ Time Frame: Up to 18 months ]
    RECIST version 1.1, until one of the discontinuation criteria is met.


Enrollment: 86
Actual Study Start Date: November 5, 2013
Study Completion Date: July 19, 2017
Primary Completion Date: July 19, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: dose escalation part
Oral
Drug: ASP5878
oral
Experimental: expansion part
Oral
Drug: ASP5878
oral

Detailed Description:
This study consists of two parts. In the dose-escalation part, ASP5878 (orally available novel small-molecule FGFR 1,2,3 and 4 inhibitor, multiple dosing once-a-day (q.d.), multiple dosing twice-a-day (b.i.d.) or 5-day on/2-day off dosing twice-a-day (5on-2off)) is administered to patients with solid tumors in an increasing dose manner, and the tolerability, safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of ASP5878 are evaluated in these patients. Cycle 0 consists of 3 days and Cycle 1 and subsequent cycles consist of 28 days each in the dose-escalation part. In the expansion part, 16mg twice-a-day 5-day on/2-day off dose of ASP5878 (5on-2off) is administered to patients with solid tumors and safety, PK, PD and efficacy of ASP5878 are evaluated. The expansion part starts from Cycle 1 and each cycle consists of 28 days.
  Eligibility

Ages Eligible for Study:   20 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed solid tumor.
  • Patient must meet at least one of the following criteria in the judgment of the investigator or sub-investigator:

    • Disease progression despite standard therapies
    • Progressive disease without any standard therapies established
    • Standard therapies are considered intolerable
  • Eastern Cooperative Oncology Group performance status 0 or 1.
  • Predicted life expectancy ≥ 12 weeks in the judgment of the investigator or sub-investigator.

Exclusion Criteria:

  • Patient with ≥ Grade 2 (CTCAE v 4.0-JCOG) persistent symptoms and objective findings due to the toxicity attributable to prior treatment with antitumor effect (except alopecia).
  • Patient who received a prior treatment intended for antitumor effect (medication, surgery, radiotherapy, etc.) within 4 weeks prior to the planned first day of study drug dosing (or patient who received mitomycin C or Nitrosourea within 6 weeks prior to the planned first day of study drug dosing).
  • A major surgical procedure within 4 weeks prior to the planned first day of study drug dosing or a surgical procedure is planned during the course of the study.
  • Patient who were treated with other investigational drug or medical device within 4 weeks prior to the planned first day of study drug dosing.
  • Patient who has a history of organ transplantation.
  • Patient with a brain metastasis with symptoms or requiring treatment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02038673

  Show 35 Study Locations
Sponsors and Collaborators
Astellas Pharma Inc
Astellas Pharma Global Development, Inc.
Investigators
Study Director: Medical Director Astellas Pharma Inc
  More Information

Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT02038673     History of Changes
Other Study ID Numbers: 5878-CL-0101
Study First Received: January 15, 2014
Last Updated: September 12, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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

Keywords provided by Astellas Pharma Inc:
ASP5878
FGFR 1,2,3 and 4 inhibitor

ClinicalTrials.gov processed this record on September 21, 2017