A Dose Escalation Study of ASP8273 in Subjects With Non-Small-Cell Lung Cancer (NSCLC) Who Have Epidermal Growth Factor Receptor (EGFR) Mutations
The purpose of this study is to assess the safety and tolerability of ASP8273 and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). This study will also determine the pharmacokinetics (PK) of ASP8273, evaluate the potential inhibition of CYP3A4 by ASP8273 and the antitumor activity of ASP8273 as well as determine the effect of food on the bioavailability of ASP8273.
Non-Small-Cell Lung Cancer (NSCLC)
Epidermal Growth Factor Receptor Mutations
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-label, Phase 1 Dose Escalation Study of Oral ASP8273 in Subjects With Non-Small-Cell Lung Cancer (NSCLC) Who Have Epidermal Growth Factor Receptor (EGFR) Mutations|
- Safety and tolerability as assessed by Dose Limiting Toxicities (DLTs) [ Time Frame: up to 18 months ] [ Designated as safety issue: Yes ]A DLT is defined as any pre-determined toxicity that is related to study drug per the investigator and which occurs during Cycle 0 and Cycle 1 using NCI CTCAE v4.03.
- Safety and tolerability as assessed by adverse events (AEs) [ Time Frame: up to 18 months ] [ Designated as safety issue: Yes ]An AE is defined as any untoward medical occurrence in a subject administered a study drug or has undergone study procedures and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
- Safety and tolerability as assessed by laboratory tests [ Time Frame: up to 18 months ] [ Designated as safety issue: Yes ]Laboratory tests to be conducted are hematology, biochemistry, urinalysis, coagulation profile, lipid panel and lymphocyte subpopulation.
- Safety and tolerability as assessed by vital signs [ Time Frame: up to 18 months ] [ Designated as safety issue: Yes ]Vital signs to be measured includes blood pressure, pulse rate and temperature.
- Safety and tolerability as assessed by 12-lead electrocardiograms (ECGs) [ Time Frame: up to 18 months ] [ Designated as safety issue: Yes ]
- Composite of pharmacokinetics of ASP8273 concentration and its metabolites (plasma): Cmax, tmax, AUClast, AUCinf, t1/2, CL/F, and Vz/F [ Time Frame: Dose Escalation: Days 1-2 of cycle 0; FE: Days 1-6 of cycle 0; Dose Escalation/ Response Expansion/ RP2D/ FE: Day 1, 8, 15 of cycle 1; RP2D: Day 21 of cycle 1; Dose Escalation/Response Expansion/ RP2D: Day 1-2 of cycle 2 and 3; FE: Day 1 of cycle 2 and 3 ] [ Designated as safety issue: No ]Maximum concentration (Cmax), the time after dosing when Cmax occurs (tmax), area under the concentration - time curve from time 0 up to the last quantifiable concentration (AUClast), area under the concentration - time curve from time 0 extrapolated to infinity (AUCinf), apparent terminal elimination half-life (t1/2), apparent oral systemic clearance (CL/F), Apparent volume of distribution (Vz/F)
- Composite of pharmacokinetics of midazolam concentration and its metabolites (plasma): Cmax, tmax, AUClast, AUCinf, t1/2, CL/F, and Vz/F [ Time Frame: Day -1 and Day 1 of cycle 1; Day 1 and Day 2 of cycle 2 ] [ Designated as safety issue: No ]
- Best overall response rate [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]Defined as proportion of subjects whose best overall response is Complete Response (CR) or Partial Response (PR) among all analyzed subjects.
- Disease control rate [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]Defined as the proportion of subjects whose best overall response is rated as CR, PR or Stable Disease (SD) among all analyzed subjects.
- Progression free survival [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]Defined as the time from the start of the study treatment until death from any cause or radiographic disease progression assessed according to RECIST 1.1, whichever occurs first.
|Study Start Date:||March 2014|
|Estimated Study Completion Date:||January 2016|
|Estimated Primary Completion Date:||November 2015 (Final data collection date for primary outcome measure)|
|Experimental: ASP8273 Dose Escalation cohort (part 1)||
|Experimental: ASP8273 Response Expansion cohort (part 1)||
|Experimental: ASP8273 and Midazolam RP2D Expansion cohort (part 2)||
|Experimental: Food Effect Fasted cohort (part 2)||
|Experimental: Food Effect Fed cohort (part 2)||
This study is composed of 2 parts: part 1 is the dose escalation phase and part 2 is the recommended Phase 2 dose (RP2D) phase and Food Effect (FE) cohort.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02113813
|Contact: Astellas Pharma Global Development||800-888-7704 ext 5473||Astellas.email@example.com|
|United States, District of Columbia|
|Georgetown University Medical Center GUMC-Lombardi Comprehensive Cancer Center LCCC||Recruiting|
|Washington, District of Columbia, United States, 20007-2113|
|United States, Maryland|
|Baltimore, Maryland, United States, 21231|
|United States, Massachusetts|
|Boston, Massachusetts, United States, 02215|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center||Recruiting|
|New York City, New York, United States, 10065|
|United States, North Carolina|
|University of North Carolina||Recruiting|
|Chapel Hill, North Carolina, United States, 27599|
|United States, Ohio|
|University Hospitals Case Medical Center||Recruiting|
|Cleveland, Ohio, United States, 44106|
|United States, Pennsylvania|
|University of Pennsylvania||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|United States, Tennessee|
|Vanderbilt University Medical Center||Recruiting|
|Nashville, Tennessee, United States, 37232-7415|
|United States, Virginia|
|Virginia Cancer Specialists, PC||Recruiting|
|Fairfax, Virginia, United States, 22031|
|United States, Washington|
|Swedish Cancer Institute Swedish Hospital||Recruiting|
|Seattle, Washington, United States, 98104|
|Study Director:||Executive Medical Director||Astellas Pharma Global Development, Inc.|