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

October 29, 2024 updated by: Astellas Pharma Inc

An Open-label Phase I Study of Oral ASP5878 at Single and Multiple Doses in Patients With Solid Tumors

The objectives of this study are to determine the tolerability, safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of oral ASP5878 in participants with solid tumors.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 participants with solid tumors in an increasing dose manner, and the tolerability, safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of ASP5878 are evaluated in these participants. 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 participants 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
86

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Chiba, Japan
        • Site JP122
      • Fukuoka, Japan
        • Site JP108
      • Fukuoka, Japan
        • Site JP115
      • Fukuoka, Japan
        • Site JP120
      • Hokkaido, Japan
        • Site JP116
      • Hyogo, Japan
        • Site JP113
      • Ibaraki, Japan
        • Site JP103
      • Ishikawa, Japan
        • Site JP111
      • Kanagawa, Japan
        • Site JP119
      • Kyoto, Japan
        • Site JP101
      • Miyagi, Japan
        • Site JP109
      • Miyagi, Japan
        • Site JP110
      • Nagoya, Japan
        • Site JP112
      • Niigata, Japan
        • Site JP117
      • Okayama, Japan
        • Site JP121
      • Osaka, Japan
        • Site JP104
      • Osaka, Japan
        • Site JP106
      • Osaka, Japan
        • Site JP118
      • Shizuoka, Japan
        • Site JP124
      • Tokyo, Japan
        • Site JP102
      • Tokyo, Japan
        • Site JP107
      • Tokyo, Japan
        • Site JP123
  • Korea, Republic of
      • Gyeonggi-do, Korea, Republic of
        • Site KR202
      • Seoul, Korea, Republic of
        • Site KR201
      • Seoul, Korea, Republic of
        • Site KR203
      • Seoul, Korea, Republic of
        • Site KR204
  • Taiwan
      • Tainan, Taiwan
        • Site TW302
      • Taipei, Taiwan
        • Site TW301
      • Taipei, Taiwan
        • Site TW303
  • United States
    • California
      • Orange, California, United States, 92868
        • Site US402
    • New York
      • New York, New York, United States, 10032
        • Site US401
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Site US404
    • South Carolina
      • Spartanburg, South Carolina, United States, 29303
        • Site US406
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Site US410
    • Washington
      • Seattle, Washington, United States, 98109
        • Site US403

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed solid tumor.

  • Participant 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:

  • Participant 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).
  • Participant 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 participant 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.
  • Participant who were treated with other investigational drug or medical device within 4 weeks prior to the planned first day of study drug dosing.
  • Participant who has a history of organ transplantation.
  • Participant with a brain metastasis with symptoms or requiring treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Dose escalation part 0.5 mg QD
Oral
Drug: ASP5878
oral
Experimental: Dose escalation part 1.0 mg QD
Oral
Drug: ASP5878
oral
Experimental: Dose escalation part 2.0 mg QD
Oral
Drug: ASP5878
oral
Experimental: Dose escalation part 2.0 mg BID
Oral
Drug: ASP5878
oral
Experimental: Dose escalation part 4.0 mg BID
Oral
Drug: ASP5878
oral
Experimental: Dose escalation part 6.0 mg BID
Oral
Drug: ASP5878
oral
Experimental: Dose escalation part 10.0 mg BID
Oral
Drug: ASP5878
oral
Experimental: Dose escalation part 20.0 mg BID
Oral
Drug: ASP5878
oral
Experimental: Dose escalation part 16.0 mg BID
Oral
Drug: ASP5878
oral
Experimental: Expansion part Urothelial Carcinoma
Oral
Drug: ASP5878
oral
Experimental: Expansion part Hepatocellular Carcinoma
Oral
Drug: ASP5878
oral
Experimental: Expansion part Squamous Cell Lung Carcinoma
Oral
Drug: ASP5878
oral

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Up to 18 months
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.
Up to 18 months
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.
Up to 18 months
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.
Up to 18 months
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.
Up to 18 months
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.
Up to 18 months
Dose-escalation part and Expansion part: Bone density measurement
Time Frame: Up to 18 months
Until one of the discontinuation criteria is met.
Up to 18 months
Dose-escalation part and Expansion part: Computed tomography (CT) Imaging assessment
Time Frame: Up to 18 months
Until one of the discontinuation criteria is met.
Up to 18 months
Expansion part only: Echocardiogram
Time Frame: Up to 18 months
Until one of the discontinuation criteria is met.
Up to 18 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
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
Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
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
Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
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
Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
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
Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
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
Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
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
Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
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
Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
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
Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
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
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 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
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
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
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 calcitriol concentrations
Time Frame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
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
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
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
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
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
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
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
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.
Up to 18 months
Expansion part: PD parameter: Serum FGF23 concentrations
Time Frame: Up to 18 months
Until one of the discontinuation criteria is met.
Up to 18 months
Expansion part: PD parameter: Serum inorganic phosphorus concentrations
Time Frame: Up to 18 months
Until one of the discontinuation criteria is met.
Up to 18 months
Expansion part: PD parameter: Serum iPTH concentrations
Time Frame: Up to 18 months
Until one of the discontinuation criteria is met.
Up to 18 months
Expansion part: PD parameter: Serum calcitriol concentrations
Time Frame: Up to 18 months
Until one of the discontinuation criteria is met.
Up to 18 months
Expansion part: PD parameter: Serum 7α-hydroxy-4-cholesten-3-one
Time Frame: Up to 18 months
Until one of the discontinuation criteria is met
Up to 18 months
Expansion part: Overall response
Time Frame: Up to 18 months
Antitumor activity evaluated based on RECIST version 1.1, until one of the discontinuation criteria is met. Antitumor response is rated on a 4-level scale shown below (complete response [CR], partial response [PR], progressive disease [PD] and stable disease [SD]).
Up to 18 months
Expansion part: Maximum Shrinkage in Target Lesion
Time Frame: Up to 18 months
Best percent change from baseline in the sum of diameters of all target lesions.
Up to 18 months
Expansion part: Progression free survival (PFS)
Time Frame: Up to 18 months
Time from the start of the study treatment until death from any cause or Progressive Disease assessed according to RECIST 1.1.
Up to 18 months
Expansion part: Time to progression (TTP)
Time Frame: Up to 18 months
Time from the start of the study treatment until Progressive Disease assessed according to RECIST 1.1.
Up to 18 months
Expansion part: Time to treatment failure (TTF)
Time Frame: Up to 18 months
Time from the start of the study drug treatment until discontinuation of study drug treatment for any reason.
Up to 18 months
Expansion part: Overall survival (OS)
Time Frame: Up to 18 months
Time from randomization to death from any cause.
Up to 18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Astellas Pharma Inc

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Astellas Pharma Global Development, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Medical Director, Astellas Pharma Inc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 5, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 19, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 19, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 15, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 15, 2014

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 16, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 31, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 29, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 5878-CL-0101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

IPD Sharing Time Frame

Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.

IPD Sharing Access Criteria

Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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