Clinical trial NCT02038673: 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
Official title: An Open-label Phase I Study of Oral ASP5878 at Single and Multiple Doses in Patients With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: ASP5878
FGFR 1,2,3 and 4 inhibitor
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Astellas Pharma Global Development, Inc.
First posted: 2014-01-16
Enrollment: 86
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose-escalation part and Expansion part: Safety assessed by Adverse Events (AEs)
timeFrame: Up to 18 months
measure: Dose-escalation part and Expansion part:Safety assessed by Vital signs
timeFrame: Up to 18 months
measure: Dose-escalation part and Expansion part:Safety assessed by Body weight
timeFrame: Up to 18 months
measure: Dose-escalation part and Expansion part:Safety assessed by Laboratory tests
timeFrame: Up to 18 months
measure: Dose-escalation part and Expansion part:Safety assessed by 12-lead ECGs
timeFrame: Up to 18 months
measure: Dose-escalation part and Expansion part: Ophthalmology
timeFrame: Up to 18 months
measure: Dose-escalation part and Expansion part: Bone density measurement
timeFrame: Up to 18 months
measure: Dose-escalation part and Expansion part: Computed tomography (CT) Imaging assessment
timeFrame: Up to 18 months
measure: Expansion part only: Echocardiogram
timeFrame: Up to 18 months
Secondary outcomes:
measure: Dose-escalation part: Pharmacokinetics (PK) parameter of ASP5878 in plasma: Cmax
timeFrame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
measure: Dose-escalation part:PK parameter of ASP5878 in plasma: tmax
timeFrame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
measure: Dose-escalation part:PK parameter of ASP5878 in plasma: AUClast
timeFrame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
measure: Dose-escalation part: PK parameter of ASP5878 in plasma: AUCinf
timeFrame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
measure: Dose-escalation part: PK parameter of ASP5878 in plasma: t1/2
timeFrame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
measure: Dose-escalation part: PK parameter of ASP5878 in plasma: CL/F
timeFrame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
measure: Dose-escalation part: PK parameter of ASP5878 in plasma: Vz/F
timeFrame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
measure: Dose-escalation part: PK parameter of ASP5878 in urine: Ae
timeFrame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
measure: Dose-escalation part: PK parameter of ASP5878 in urine: CLR
timeFrame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
measure: Dose-escalation part: Pharmacodynamic (PD) parameter: Serum FGF23 concentrations
timeFrame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
measure: Dose-escalation part: PD parameter: Serum inorganic phosphorus concentrations
timeFrame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
measure: Dose-escalation part: PD parameter: Serum calcium concentrations
timeFrame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
measure: Dose-escalation part: PD parameter: Serum iPTH concentrations
timeFrame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
measure: Dose-escalation part: PD parameter: Serum calcitriol concentrations
timeFrame: Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
measure: Expansion part: PK parameter of ASP5878 in plasma: Cmax
timeFrame: Day 1 and 5 at Cycle 1
measure: Expansion part: PK parameter of ASP5878 in plasma: tmax
timeFrame: Day 1 and 5 at Cycle 1
measure: Expansion part: PK parameter of ASP5878 in plasma: AUClast
timeFrame: Day 1 and 5 at Cycle 1
measure: Expansion part: PK parameter of ASP5878 in plasma: AUCinf
timeFrame: Day 1 and 5 at Cycle 1
measure: Expansion part: PK parameter of ASP5878 in plasma: t1/2
timeFrame: Day 1 and 5 at Cycle 1
measure: Expansion part: PK parameter of ASP5878 in plasma: CL/F
timeFrame: Day 1 and 5 at Cycle 1
measure: Expansion part: PK parameter of ASP5878 in plasma: Vz/F
timeFrame: Day 1 and 5 at Cycle 1
measure: Expansion part: PD parameter: Serum FGF19 concentrations
timeFrame: Up to 18 months
measure: Expansion part: PD parameter: Serum FGF23 concentrations
timeFrame: Up to 18 months
measure: Expansion part: PD parameter: Serum inorganic phosphorus concentrations
timeFrame: Up to 18 months
measure: Expansion part: PD parameter: Serum iPTH concentrations
timeFrame: Up to 18 months
measure: Expansion part: PD parameter: Serum calcitriol concentrations
timeFrame: Up to 18 months
measure: Expansion part: PD parameter: Serum 7α-hydroxy-4-cholesten-3-one
timeFrame: Up to 18 months
measure: Expansion part: Overall response
timeFrame: Up to 18 months
measure: Expansion part: Maximum Shrinkage in Target Lesion
timeFrame: Up to 18 months
measure: Expansion part: Progression free survival (PFS)
timeFrame: Up to 18 months
measure: Expansion part: Time to progression (TTP)
timeFrame: Up to 18 months
measure: Expansion part: Time to treatment failure (TTF)
timeFrame: Up to 18 months
measure: Expansion part: Overall survival (OS)
timeFrame: Up to 18 months
Other outcomes:
Locations:
city: Orange
country: United States
facility: Site US402
state: California
city: New York
country: United States
facility: Site US401
state: New York
city: Cleveland
country: United States
facility: Site US404
state: Ohio
city: Spartanburg
country: United States
facility: Site US406
state: South Carolina
city: Fairfax
country: United States
facility: Site US410
state: Virginia
city: Seattle
country: United States
facility: Site US403
state: Washington
city: Chiba
country: Japan
facility: Site JP122
city: Fukuoka
country: Japan
facility: Site JP108
city: Fukuoka
country: Japan
facility: Site JP115
city: Fukuoka
country: Japan
facility: Site JP120
city: Hokkaido
country: Japan
facility: Site JP116
city: Hyogo
country: Japan
facility: Site JP113
city: Ibaraki
country: Japan
facility: Site JP103
city: Ishikawa
country: Japan
facility: Site JP111
city: Kanagawa
country: Japan
facility: Site JP119
city: Kyoto
country: Japan
facility: Site JP101
city: Miyagi
country: Japan
facility: Site JP109
city: Miyagi
country: Japan
facility: Site JP110
city: Nagoya
country: Japan
facility: Site JP112
city: Niigata
country: Japan
facility: Site JP117
city: Okayama
country: Japan
facility: Site JP121
city: Osaka
country: Japan
facility: Site JP104
city: Osaka
country: Japan
facility: Site JP106
city: Osaka
country: Japan
facility: Site JP118
city: Shizuoka
country: Japan
facility: Site JP124
city: Tokyo
country: Japan
facility: Site JP102
city: Tokyo
country: Japan
facility: Site JP107
city: Tokyo
country: Japan
facility: Site JP123
city: Gyeonggi-do
country: Korea, Republic of
facility: Site KR202
city: Seoul
country: Korea, Republic of
facility: Site KR201
city: Seoul
country: Korea, Republic of
facility: Site KR203
city: Seoul
country: Korea, Republic of
facility: Site KR204
city: Tainan
country: Taiwan
facility: Site TW302
city: Taipei
country: Taiwan
facility: Site TW301
city: Taipei
country: Taiwan
facility: Site TW303
Study officials:
affiliation: Astellas Pharma Inc
name: Medical Director
role: STUDY_DIRECTOR
References: