Solid Tumors
Conditions
Keywords
ASP5878, FGFR 1,2,3 and 4 inhibitor
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.
Interventions
DRUGASP5878
oral
Sponsors
Astellas Pharma Global Development, Inc.
Astellas Pharma Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-escalation part and Expansion part: Safety assessed by Adverse Events (AEs) | Up to 18 months | Until one of the discontinuation criteria is met. |
| Dose-escalation part and Expansion part:Safety assessed by Vital signs | 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:Safety assessed by Body weight | Up to 18 months | Until one of the discontinuation criteria is met. |
| Dose-escalation part and Expansion part:Safety assessed by Laboratory tests | Up to 18 months | Hematology, blood biochemistry, blood coagulation tests and urinalysis, until one of the discontinuation criteria is met. |
| Dose-escalation part and Expansion part:Safety assessed by 12-lead ECGs | Up to 18 months | ECG: Electrocardiogram, until one of the discontinuation criteria is met. |
| Dose-escalation part and Expansion part: Ophthalmology | 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: Bone density measurement | Up to 18 months | Until one of the discontinuation criteria is met. |
| Dose-escalation part and Expansion part: Computed tomography (CT) Imaging assessment | Up to 18 months | Until one of the discontinuation criteria is met. |
| Expansion part only: Echocardiogram | Up to 18 months | Until one of the discontinuation criteria is met. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | iPTH: Intact Parathyroid Hormone |
| 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: PK parameter of ASP5878 in plasma: Cmax | Day 1 and 5 at Cycle 1 | — |
| Expansion part: PK parameter of ASP5878 in plasma: tmax | Day 1 and 5 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 | Cmax: Maximum concentration, Cycle 0: single dose, Cycle 1: multiple dose after Cycle 0 |
| 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 | tmax: Time of Cmax |
| 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 | AUClast: Area under the concentration-time curve from the time of dosing extrapolated to the last measurable concentration |
| 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 | AUCinf: Area under the concentration-time curve from the time of dosing extrapolated to time infinity |
| 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 | t1/2: Terminal elimination half-life |
| 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 | CL/F: Apparent total systemic clearance |
| 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 | Vz/F: Apparent volume of distribution during the terminal elimination phase |
| 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 | Ae: Amount of ASP5878 excreted into the urine |
| 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 | CLR: Renal clearance |
| Expansion part: PK parameter of ASP5878 in plasma: AUClast | Day 1 and 5 at Cycle 1 | — |
| Expansion part: PD parameter: Serum inorganic phosphorus concentrations | Up to 18 months | Until one of the discontinuation criteria is met. |
| Expansion part: PD parameter: Serum iPTH concentrations | Up to 18 months | Until one of the discontinuation criteria is met. |
| Expansion part: PD parameter: Serum calcitriol concentrations | Up to 18 months | Until one of the discontinuation criteria is met. |
| Expansion part: PK parameter of ASP5878 in plasma: AUCinf | Day 1 and 5 at Cycle 1 | — |
| Expansion part: Overall response | 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 \[SD\]). |
| Expansion part: Maximum Shrinkage in Target Lesion | Up to 18 months | Best percent change from baseline in the sum of diameters of all target lesions. |
| Expansion part: Progression free survival (PFS) | 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. |
| Expansion part: Time to progression (TTP) | Up to 18 months | Time from the start of the study treatment until Progressive Disease assessed according to RECIST 1.1. |
| Expansion part: Time to treatment failure (TTF) | Up to 18 months | Time from the start of the study drug treatment until discontinuation of study drug treatment for any reason. |
| Expansion part: Overall survival (OS) | Up to 18 months | Time from randomization to death from any cause. |
| Expansion part: PD parameter: Serum 7α-hydroxy-4-cholesten-3-one | Up to 18 months | Until one of the discontinuation criteria is met |
| 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: PK parameter of ASP5878 in plasma: Vz/F | Day 1 and 5 at Cycle 1 | — |
| Expansion part: PD parameter: Serum FGF19 concentrations | Up to 18 months | Until one of the discontinuation criteria is met. |
| Expansion part: PD parameter: Serum FGF23 concentrations | Up to 18 months | Until one of the discontinuation criteria is met. |
| 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 | FGF: Fibroblast Growth Factor |
| 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 | — |
| 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 | — |
Countries
Japan, South Korea, Taiwan, United States
Outcome results
None listed