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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02038673
• Date of registration: 15/01/2014
• Prospective Registration: No
• Primary sponsor: Astellas Pharma Inc
• Public title: 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
• Scientific title: An Open-label Phase I Study of Oral ASP5878 at Single and Multiple Doses in Patients With Solid Tumors
• Date of first enrolment: November 5, 2013
• Target sample size: 86
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02038673
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

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

Contacts

• Name: Medical Director
• Affiliation: Astellas Pharma Inc

Key inclusion & exclusion 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.



Age minimum: 20 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Solid Tumors

Intervention(s)

Drug: ASP5878

Primary Outcome(s)

Dose-escalation part and Expansion part:Safety assessed by Vital signs [Time Frame: Up to 18 months]

Dose-escalation part and Expansion part:Safety assessed by 12-lead ECGs [Time Frame: Up to 18 months]

Dose-escalation part and Expansion part:Safety assessed by Body weight [Time Frame: Up to 18 months]

Dose-escalation part and Expansion part: Computed tomography (CT) Imaging assessment [Time Frame: Up to 18 months]

Dose-escalation part and Expansion part: Ophthalmology [Time Frame: Up to 18 months]

Dose-escalation part and Expansion part:Safety assessed by Laboratory tests [Time Frame: Up to 18 months]

Dose-escalation part and Expansion part: Bone density measurement [Time Frame: Up to 18 months]

Dose-escalation part and Expansion part: Safety assessed by Adverse Events (AEs) [Time Frame: Up to 18 months]

Expansion part only: Echocardiogram [Time Frame: Up to 18 months]

Secondary Outcome(s)

Expansion part: Time to treatment failure (TTF) [Time Frame: Up to 18 months]

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]

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]

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]

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]

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: 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]

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]

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]

Expansion part: PD parameter: Serum calcitriol concentrations [Time Frame: Up to 18 months]

Expansion part: PK parameter of ASP5878 in plasma: CL/F [Time Frame: Day 1 and 5 at Cycle 1]

Expansion part: PD parameter: Serum iPTH concentrations [Time Frame: Up to 18 months]

Expansion part: PK parameter of ASP5878 in plasma: t1/2 [Time Frame: Day 1 and 5 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]

Expansion part: PD parameter: Serum FGF23 concentrations [Time Frame: Up to 18 months]

Expansion part: Progression free survival (PFS) [Time Frame: Up to 18 months]

Expansion part: PK parameter of ASP5878 in plasma: Cmax [Time Frame: Day 1 and 5 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]

Expansion part: PD parameter: Serum 7a-hydroxy-4-cholesten-3-one [Time Frame: Up to 18 months]

Expansion part: PD parameter: Serum inorganic phosphorus concentrations [Time Frame: Up to 18 months]

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: AUClast [Time Frame: Day 1 and 5 at Cycle 1]

Expansion part: Time to progression (TTP) [Time Frame: Up to 18 months]

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: Vz/F [Time Frame: Day 1 and 5 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]

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]

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]

Expansion part: Maximum Shrinkage in Target Lesion [Time Frame: Up to 18 months]

Expansion part: Overall response [Time Frame: Up to 18 months]

Expansion part: Overall survival (OS) [Time Frame: Up to 18 months]

Expansion part: PD parameter: Serum FGF19 concentrations [Time Frame: Up to 18 months]

Secondary ID(s)

5878-CL-0101

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Astellas Pharma Global Development, Inc.