Study to Investigate the Absorption, Metabolism and Excretion of [14C] ASP2215 in Patients With Advanced Solid Tumors

A Phase 1, Open-label Study to Investigate the Absorption, Metabolism and Excretion of [14C] ASP2215 in Patients With Advanced Solid Tumors

The purpose of this study is to evaluate the pharmacokinetics of 14C-labeled gilteritinib, in particular, the routes of excretion and extent of metabolism of gilteritinib following administration of a single dose of 14C-labeled gilteritinib after repeated doses of gilteritinib.

This study will also evaluate the safety of repeated oral administration of gilteritinib in subjects with advanced solid tumors as well as identify the metabolic profile of gilteritinib in plasma, urine and feces after a single oral dose of 14C-labeled gilteritinib.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors; Pharmacokinetics of 14C-labeled Gilteritinib
• Intervention / Treatment: Drug: gilteritinib; Drug: 14C-labeled gilteritinib

Detailed Description

Participants will be admitted for evaluation to the clinical research unit on day 14 for potentially up to 14 days (day 29). At approximately days 36 and 45 participants will return to the clinic (for 3 days) for additional sample collection.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Expanded Access

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Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Site US10001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject had histologically or cytologically confirmed diagnosis of advanced solid tumor (measurable or nonmeasurable disease) for which no standard therapy is available.
• Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
• Subject must have a life expectancy > 12 weeks.
• Subject must have recovered from the effects of prior systemic antineoplastic or radiation therapy(s) to ≤ Grade 1 (National Cancer Institute - Common Terminology Criteria for Adverse Events [NCI-CTCAE], Version 4.0) severity or to subject's baseline values, excluding alopecia.

• Subject has adequate bone marrow, renal and hepatic function at baseline, as demonstrated by the following:

  • Absolute neutrophil count (ANC) ≥ 1500 cells/mm3
  • Platelet count ≥ 100,000 cells/mm3
  • Hemoglobin (Hb) ≥ 9 g/dL
  • Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance > 60 mL/min if the serum creatinine is > 1.5 x ULN
  • Total bilirubin ≤ 1.5 x ULN
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 3 x ULN (or < 5 x ULN in subjects with liver metastases or hepatocellular carcinoma).

• Female subject must either:

  • Be of nonchildbearing potential: postmenopausal (defined as at least 1 year without any menses) prior to screening, or documented surgically sterile
  • Or, if of childbearing potential: agree not to try to become pregnant during the study and for 60 days after the final study drug administration and have a negative serum or urine pregnancy test at screening, and if heterosexually active, agree to consistently use 2 forms of birth control (at least one of which must be a barrier method) starting at screening and throughout the study period and for 60 days after final study drug administration.
• Female subject must not be breastfeeding at screening or during the study period, and for 60 days after the final study drug administration.
• Female subject must not donate ova starting at screening and throughout the study period and for 60 days after final study drug administration.
• Male subject and a female spouse/partner who is of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control (one of which must be a barrier method) starting at screening and continue throughout the study period and for 120 days after the final study drug administration.
• Male subject must not donate sperm starting at screening and throughout the study period and for 120 days after final study drug administration.
• Subject must be willing to comply with all procedures and assessments.

Exclusion Criteria:

• Subject has received more than 5 prior cytotoxic agent-containing regimens.

• Subject has symptomatic central nervous system (CNS) metastases or leptomeningeal involvement as assessed through medical history review and physical examination. Subject with prior brain metastases must:

  • have stable neurologic status post administration of local therapy (surgery or radiation) for a minimum of 2 weeks following completion of the definitive therapy.
  • be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events (AEs).
• Subject has had major surgery within 4 weeks prior to the first study dose.
• Subject has had chemotherapy within 4 weeks prior to the first study dose.
• Subject has had radiation therapy within 4 weeks prior to the first study dose.
• Subject with known hepatitis B surface antigen (HBsAg) positive status; or known or suspected active hepatitis C infection; or known human immunodeficiency virus (HIV) positive.
• Subject with malabsorption syndrome or disease or condition significantly affecting gastrointestinal function.
• Subject with significant or uncontrolled cardiac, renal, hepatic or other systemic disorders; or significant psychological conditions at baseline that in the investigator's opinion, makes the subject unsuitable for study participation.
• Subject with electrocardiogram (ECG) abnormalities on a 12-lead ECG performed within 14 days before start of the study drug that are considered by the Investigator to be clinically significant.
• Subject who has received strong or moderate inhibitors (e.g., ketoconazole or fluconazole) or inducers (e.g., rifampin or phenytoin) of cytochrome P450 (CYP)3A4 or of P-glycoprotein (P-gp), or substrates of multidrug and toxin extrusion (MATE)1 with the exception of antibiotics, antifungals, and antivirals that are used as standard of care post transplant or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the subject within 2 weeks prior to start of study treatment and while on study.
• Subject requires treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR receptors or sigma nonspecific receptor, with the exception of drugs that are considered absolutely essential for the care of the subject.
• Subject has participated in any interventional clinical study or has been treated with any investigational drugs within 30 days or 5 half-lives, whichever is longer, prior to the initiation of screening.
• Subject has a known history of serious hypersensitivity to ASP2215, or any component of the formulation used.
• Subject who has an ongoing toxicity ≥ Grade 2 (Common Terminology Criteria for Adverse Event [CTCAE] v4.03) attributable to prior medication to treat solid tumor (except alopecia) at the time of screening.

• Subject has had any of the following within 14 days prior to the first dose of study drug:

  • blood transfusion or hemopoietic factor therapy
  • evidence of active infection requiring systemic therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: gilteritinib and 14C-labeled gilteritinib; Gilteritinib will be taken once daily on study days 1 through 14 and days 16 through 47. On day 15, each participant will be given a single dose of 14C-labeled gilteritinib.	Drug: gilteritinib; oral; Other Names: ASP2215; Drug: 14C-labeled gilteritinib; oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of 14C-labeled gilteritinib (Radioactivity in whole blood): AUCtau	Area under the concentration curve over the dosing interval (AUCtau)	Days 15 - 46
Pharmacokinetics of 14C-labeled gilteritinib (Radioactivity in whole blood): Cmax	Maximum concentration (Cmax)	Days 15 - 46
Pharmacokinetics of 14C-labeled gilteritinib (Radioactivity in whole blood): tmax	Time of maximum concentration (tmax)	Days 15 - 46
Pharmacokinetics of 14C-labeled gilteritinib (Radioactivity in whole blood): t1/2	Terminal elimination half-life (t1/2)	Days 15 - 46
Pharmacokinetics of 14C-labeled gilteritinib (Radioactivity in whole blood): CL/F	Apparent body clearance after extravascular dosing (CL/F)	Days 15 - 46
Pharmacokinetics of 14C-labeled gilteritinib (Radioactivity in plasma): AUCtau		Days 15 - 46
Pharmacokinetics of 14C-labeled gilteritinib (Radioactivity in plasma): Cmax		Days 15 - 46
Pharmacokinetics of 14C-labeled gilteritinib (Radioactivity in plasma): tmax		Days 15 - 46
Pharmacokinetics of 14C-labeled gilteritinib (Radioactivity in plasma): t1/2		Days 15 - 46
Pharmacokinetics of 14C-labeled gilteritinib (Radioactivity in plasma): CL/F		Days 15 - 46
Pharmacokinetics of 14C-labeled gilteritinib (Radioactivity ratio of whole blood/plasma concentrations): AUC	Area under the concentration (AUC)	Days 15 - 46
Excretion rate of 14C-labeled gilteritinib (radioactivity in urine)	Percent of dose excreted in urine	Days 15 - 46
Cumulative excretion of 14C-labeled gilteritinib (radioactivity in urine)	Cumulative total of radioactivity excreted in urine	Days 15 - 46
Excretion rate of 14C-labeled gilteritinib (radioactivity in feces)	Percent of dose excreted in feces	Days 15 - 46
Cumulative excretion of 14C-labeled gilteritinib (radioactivity in feces)	Cumulative total of radioactivity excreted in feces	Days 15 - 46
Pharmacokinetics of gilteritinib (in plasma): AUCtau		Days 15 - 46
Pharmacokinetics of gilteritinib (in plasma): Cmax		Days 15 - 46
Pharmacokinetics of gilteritinib (in plasma): tmax		Days 15 - 46
Pharmacokinetics of gilteritinib (in plasma): CL/F		Days 15 - 46
Pharmacokinetics of gilteritinib (in urine): Aetau	Cumulative amount of study drug excreted into urine from the time of dosing to the start of the next dosing interval (Aetau)	Days 15 - 46
Pharmacokinetics of gilteritinib (in urine): CLR	Renal clearance (CLR)	Days 15 - 46
Pharmacokinetics of gilteritinib (in urine): AETAU%	Percentage of study drug dose excreted into urine over the time interval between consecutive dosing (AETAU%)	Days 15 - 46

Secondary Outcome Measures

Outcome Measure	Time Frame
Metabolite identification of gilteritinib in plasma, urine and feces	Days 15 - 46

Collaborators and Investigators

• Sponsor: Astellas Pharma Global Development, Inc.
• Investigators: Study Director: Medical Director, Astellas Pharma Global Development, Inc.

Publications and helpful links

General Publications

• James AJ, Smith CC, Litzow M, Perl AE, Altman JK, Shepard D, Kadokura T, Souda K, Patton M, Lu Z, Liu C, Moy S, Levis MJ, Bahceci E. Pharmacokinetic Profile of Gilteritinib: A Novel FLT-3 Tyrosine Kinase Inhibitor. Clin Pharmacokinet. 2020 Oct;59(10):1273-1290. doi: 10.1007/s40262-020-00888-w. Erratum In: Clin Pharmacokinet. 2021 Sep;60(9):1251. doi: 10.1007/s40262-021-01060-8.

Helpful Links

• Link to results on the Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2016
• Primary Completion (Actual): May 20, 2017
• Study Completion (Actual): June 19, 2017

Study Registration Dates

• First Submitted: May 27, 2015
• First Submitted That Met QC Criteria: May 27, 2015
• First Posted (Estimated): May 29, 2015

Study Record Updates

• Last Update Posted (Actual): November 5, 2024
• Last Update Submitted That Met QC Criteria: November 1, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Advanced Solid Tumors; gilteritinib; ASP2215; 14C-labeled gilteritinib
• Additional Relevant MeSH Terms: Neoplasms; Tyrosine Kinase Inhibitors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Gilteritinib
• Other Study ID Numbers: 2215-CL-0105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.