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

Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02038673
• Other study ID #: 5878-CL-0101
• Status: Completed
• Phase: Phase 1
• Start date: November 5, 2013
• Est. completion date: July 19, 2017

Study information

• Verified date: October 2018
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: July 19, 2017
• Est. primary completion date: July 19, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Solid Tumors

Intervention

Drug:
• ASP5878
oral

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Inc	Astellas Pharma Global Development, Inc.

Countries where clinical trial is conducted

United States,  Japan,  Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-escalation part and Expansion part: Safety assessed by Adverse Events (AEs)	Until one of the discontinuation criteria is met.	Up to 18 months
Primary	Dose-escalation part and Expansion part:Safety assessed by Vital signs	Blood pressure, pulse rate and body temperature, Until one of the discontinuation criteria is met.	Up to 18 months
Primary	Dose-escalation part and Expansion part:Safety assessed by Body weight	Until one of the discontinuation criteria is met.	Up to 18 months
Primary	Dose-escalation part and Expansion part:Safety assessed by Laboratory tests	Hematology, blood biochemistry, blood coagulation tests and urinalysis, until one of the discontinuation criteria is met.	Up to 18 months
Primary	Dose-escalation part and Expansion part:Safety assessed by 12-lead ECGs	ECG: Electrocardiogram, until one of the discontinuation criteria is met.	Up to 18 months
Primary	Dose-escalation part and Expansion part: Ophthalmology	Eyesight, funduscopy, slit lamp microscopy, and Optical Coherence Tomography, until one of the discontinuation criteria is met.	Up to 18 months
Primary	Dose-escalation part and Expansion part: Bone density measurement	Until one of the discontinuation criteria is met.	Up to 18 months
Primary	Dose-escalation part and Expansion part: Computed tomography (CT) Imaging assessment	Until one of the discontinuation criteria is met.	Up to 18 months
Primary	Expansion part only: Echocardiogram	Until one of the discontinuation criteria is met.	Up to 18 months
Secondary	Dose-escalation part: Pharmacokinetics (PK) parameter of ASP5878 in plasma: Cmax	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
Secondary	Dose-escalation part:PK parameter of ASP5878 in plasma: tmax	tmax: Time of Cmax	Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
Secondary	Dose-escalation part:PK parameter of ASP5878 in plasma: AUClast	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
Secondary	Dose-escalation part: PK parameter of ASP5878 in plasma: AUCinf	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
Secondary	Dose-escalation part: PK parameter of ASP5878 in plasma: t1/2	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
Secondary	Dose-escalation part: PK parameter of ASP5878 in plasma: CL/F	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
Secondary	Dose-escalation part: PK parameter of ASP5878 in plasma: Vz/F	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
Secondary	Dose-escalation part: PK parameter of ASP5878 in urine: Ae	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
Secondary	Dose-escalation part: PK parameter of ASP5878 in urine: CLR	CLR: Renal clearance	Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
Secondary	Dose-escalation part: Pharmacodynamic (PD) parameter: Serum FGF23 concentrations	FGF: Fibroblast Growth Factor	Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
Secondary	Dose-escalation part: PD parameter: Serum inorganic phosphorus concentrations		Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
Secondary	Dose-escalation part: PD parameter: Serum calcium concentrations		Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
Secondary	Dose-escalation part: PD parameter: Serum iPTH concentrations	iPTH: Intact Parathyroid Hormone	Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
Secondary	Dose-escalation part: PD parameter: Serum calcitriol concentrations		Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1
Secondary	Expansion part: PK parameter of ASP5878 in plasma: Cmax		Day 1 and 5 at Cycle 1
Secondary	Expansion part: PK parameter of ASP5878 in plasma: tmax		Day 1 and 5 at Cycle 1
Secondary	Expansion part: PK parameter of ASP5878 in plasma: AUClast		Day 1 and 5 at Cycle 1
Secondary	Expansion part: PK parameter of ASP5878 in plasma: AUCinf		Day 1 and 5 at Cycle 1
Secondary	Expansion part: PK parameter of ASP5878 in plasma: t1/2		Day 1 and 5 at Cycle 1
Secondary	Expansion part: PK parameter of ASP5878 in plasma: CL/F		Day 1 and 5 at Cycle 1
Secondary	Expansion part: PK parameter of ASP5878 in plasma: Vz/F		Day 1 and 5 at Cycle 1
Secondary	Expansion part: PD parameter: Serum FGF19 concentrations	Until one of the discontinuation criteria is met.	Up to 18 months
Secondary	Expansion part: PD parameter: Serum FGF23 concentrations	Until one of the discontinuation criteria is met.	Up to 18 months
Secondary	Expansion part: PD parameter: Serum inorganic phosphorus concentrations	Until one of the discontinuation criteria is met.	Up to 18 months
Secondary	Expansion part: PD parameter: Serum iPTH concentrations	Until one of the discontinuation criteria is met.	Up to 18 months
Secondary	Expansion part: PD parameter: Serum calcitriol concentrations	Until one of the discontinuation criteria is met.	Up to 18 months
Secondary	Expansion part: PD parameter: Serum 7a-hydroxy-4-cholesten-3-one	Until one of the discontinuation criteria is met	Up to 18 months
Secondary	Expansion part: Overall response	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
Secondary	Expansion part: Maximum Shrinkage in Target Lesion	Best percent change from baseline in the sum of diameters of all target lesions.	Up to 18 months
Secondary	Expansion part: Progression free survival (PFS)	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
Secondary	Expansion part: Time to progression (TTP)	Time from the start of the study treatment until Progressive Disease assessed according to RECIST 1.1.	Up to 18 months
Secondary	Expansion part: Time to treatment failure (TTF)	Time from the start of the study drug treatment until discontinuation of study drug treatment for any reason.	Up to 18 months
Secondary	Expansion part: Overall survival (OS)	Time from randomization to death from any cause.	Up to 18 months

External Links

•   Link to results on the Astellas Clinical Study Results website