An Open-label Phase I Study of Oral ASP5878 at Single and Multiple Doses in Patients With Solid Tumors
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Astellas Pharma Inc
- Enrollment
- 86
- Locations
- 35
- Primary Endpoint
- Dose-escalation part and Expansion part:Safety assessed by Body weight
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 20 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- •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.
Arms & Interventions
Dose escalation part 20.0 mg BID
Oral
Intervention: ASP5878 (Drug)
Dose escalation part 0.5 mg QD
Oral
Intervention: ASP5878 (Drug)
Dose escalation part 1.0 mg QD
Oral
Intervention: ASP5878 (Drug)
Dose escalation part 2.0 mg QD
Oral
Intervention: ASP5878 (Drug)
Dose escalation part 2.0 mg BID
Oral
Intervention: ASP5878 (Drug)
Dose escalation part 4.0 mg BID
Oral
Intervention: ASP5878 (Drug)
Dose escalation part 6.0 mg BID
Oral
Intervention: ASP5878 (Drug)
Dose escalation part 10.0 mg BID
Oral
Intervention: ASP5878 (Drug)
Dose escalation part 16.0 mg BID
Oral
Intervention: ASP5878 (Drug)
Expansion part Urothelial Carcinoma
Oral
Intervention: ASP5878 (Drug)
Expansion part Hepatocellular Carcinoma
Oral
Intervention: ASP5878 (Drug)
Expansion part Squamous Cell Lung Carcinoma
Oral
Intervention: ASP5878 (Drug)
Outcomes
Primary Outcomes
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: Computed tomography (CT) Imaging assessment
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: 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: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.
Expansion part only: Echocardiogram
Time Frame: Up to 18 months
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: 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: Bone density measurement
Time Frame: Up to 18 months
Until one of the discontinuation criteria is met.
Secondary Outcomes
- Dose-escalation part:PK parameter of ASP5878 in plasma: tmax(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(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(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: AUCinf(Day 1 and 5 at Cycle 1)
- Expansion part: PK parameter of ASP5878 in plasma: Vz/F(Day 1 and 5 at Cycle 1)
- Expansion part: PD parameter: Serum FGF23 concentrations(Up to 18 months)
- Expansion part: PD parameter: Serum iPTH concentrations(Up to 18 months)
- Expansion part: PD parameter: Serum calcitriol concentrations(Up to 18 months)
- Dose-escalation part: PK parameter of ASP5878 in urine: Ae(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(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(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(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(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(Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1)
- Expansion part: Progression free survival (PFS)(Up to 18 months)
- Dose-escalation part: PK parameter of ASP5878 in plasma: CL/F(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(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(Day 1 and 5 at Cycle 1)
- Expansion part: PK parameter of ASP5878 in plasma: AUClast(Day 1 and 5 at Cycle 1)
- Expansion part: PK parameter of ASP5878 in plasma: t1/2(Day 1 and 5 at Cycle 1)
- Expansion part: PK parameter of ASP5878 in plasma: CL/F(Day 1 and 5 at Cycle 1)
- Expansion part: PD parameter: Serum 7α-hydroxy-4-cholesten-3-one(Up to 18 months)
- Expansion part: Overall response(Up to 18 months)
- Expansion part: Maximum Shrinkage in Target Lesion(Up to 18 months)
- Expansion part: Overall survival (OS)(Up to 18 months)
- Dose-escalation part: PK parameter of ASP5878 in urine: CLR(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 FGF19 concentrations(Up to 18 months)
- Expansion part: Time to progression (TTP)(Up to 18 months)
- Dose-escalation part: Pharmacodynamic (PD) parameter: Serum FGF23 concentrations(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(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: tmax(Day 1 and 5 at Cycle 1)
- Expansion part: PD parameter: Serum inorganic phosphorus concentrations(Up to 18 months)
- Expansion part: Time to treatment failure (TTF)(Up to 18 months)