A Study of ASP8273 in Subjects With Non-small Cell Lung Cancer (NSCLC) Harboring Epidermal Growth Factor Receptor (EGFR) Mutations

NCT03082300 | Terminated Phase 1 FDA Drug

• 1 other identifier: 8273-CL-0112
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 3

Brief Summary

The objective of this study is to evaluate the bioequivalence of a tablet formulation versus a capsule formulation of ASP8273 following a single dose under fasted condition in subjects with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. The study will also evaluate the safety and tolerability of a tablet formulation as a single dose and a capsule formulation as a single and multiple dose of ASP8273 in subjects with NSCLC harboring EGFR mutations.

Conditions

Non-small Cell Lung Cancer (NSCLC); Epidermal Growth Factor Receptor (EGFR) Mutations

Keywords

ASP8273; Epidermal growth factor receptor (EGFR) mutations; naquotinib; Non-small cell lung cancer (NSCLC); Bioequivalence

Outcome Measures

Primary Outcomes (4)

• Pharmacokinetics of ASP8273 in plasma: Cmax

  Cmax: Maximum plasma concentration. Pharmacokinetic phase only

  Up to Day 5 in each period of Phase 1 (maximum of 10 days)

• Pharmacokinetics of ASP8273 in plasma: AUCinf

  AUCinf: Area under the concentration time curve extrapolated to time infinity. Pharmacokinetic phase only

  Up to Day 5 in each period of Phase 1 (maximum of 10 days)

• Pharmacokinetics of ASP8273 in plasma: AUClast

  AUClast: Area under the concentration time curve from time zero to the last quantifiable concentration. Pharmacokinetic phase only

  Up to Day 5 in each period of Phase 1 (maximum of 10 days)

• Pharmacokinetics of ASP8273 in plasma: AUC72

  AUC72: Area under the concentration time curve truncated at 72 hours. Pharmacokinetic phase only

  Up to Day 5 in each period of Phase 1 (maximum of 10 days)

Secondary Outcomes (9)

• Pharmacokinetics of ASP8273 in plasma: t1/2

  Up to Day 5 in each period of Phase 1 (maximum of 10 days)

• Pharmacokinetics of ASP8273 in plasma: tmax

  Up to Day 5 in each period of Phase 1 (maximum of 10 days)

• Pharmacokinetics of ASP8273 in plasma: tlast

  Up to Day 5 in each period of Phase 1 (maximum of 10 days)

• Pharmacokinetics of ASP8273 in plasma: CL/F

  Up to Day 5 in each period of Phase 1 (maximum of 10 days)

• Pharmacokinetics of ASP8273 in plasma: Vz/F

  Up to Day 5 in each period of Phase 1 (maximum of 10 days)

Study Arms (3)

Pharmacokinetic phase: ASP8273 Tablet then Capsule Sequence

EXPERIMENTAL

Subjects will receive a single oral dose in tablet formulation on Day 1 of period 1 under fasted condition, then subjects will receive a single oral dose of ASP8273 in capsule formulation on Day 1 of period 2 under fasted condition. Each period will be for 5 days

Drug: naquotinib

Pharmacokinetic phase: ASP8273 Capsule then Tablet Sequence

EXPERIMENTAL

Subjects will receive a single oral dose in capsule formulation on Day 1 of period 1 under fasted condition, then subjects will receive a single oral dose of ASP8273 in tablet formulation on Day 1 of period 2 under fasted condition. Each period will be for 5 days

Drug: naquotinib

Postpharmacokinetic phase: ASP8273 Capsule Formulation

EXPERIMENTAL

All subjects will receive ASP8273 capsules in once-daily dosing for 1 cycle (28 days)

Drug: naquotinib

Interventions

naquotinib DRUG

Oral

Also known as: ASP8273

Pharmacokinetic phase: ASP8273 Capsule then Tablet Sequence; Pharmacokinetic phase: ASP8273 Tablet then Capsule Sequence; Postpharmacokinetic phase: ASP8273 Capsule Formulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has histologically confirmed locally advanced or unresectable Stage IIIB (not amenable to receive curative treatments such as chemo-radiation)/IV or metastatic NSCLC.
• Subject has Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Subject has an EGFR activating mutation based on local testing.
• Subject has predicted life expectancy ≥ 12 weeks.
• Subject must meet all of the following criteria on the laboratory tests. In case of multiple laboratory data within this period, the most recent data should be used.
• Neutrophil count \> 1000/mm\^3
• Platelet count ≥ 7.5 x 10\^4/mm\^3
• Hemoglobin \> 8.0 g/dL
• Serum creatinine \<2.0 x upper limit of normal (ULN) or estimated glomerular filtration rate of \> 50 mL/min as calculated by the Cockcroft Gault Method
• Total bilirubin \< 1.5 × ULN (except for subjects with documented Gilbert's syndrome)
• AST (Aspartate aminotransferase (GOT) and ALT (Alanine aminotransferase (GPT)) \< 3.0 × ULN (upper limit of normal) or ≤ 5 × ULN if subject has documented liver metastases
• Serum sodium level ≥ 130 mmol/L
• Subject agrees not to participate in another interventional study while receiving study drug and participating in the present study.
• Female subject must either:
• Be of nonchildbearing potential:

You may not qualify if:

• Subject has an ongoing toxicity ≥ Grade 2 (NCI CTCAE Version 4.03) attributable to prior medication to treat solid tumor (except alopecia) at screening.
• Subject has received investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study drug.
• Subject has received treatment with any other agent with antitumor activity including chemotherapy, radiotherapy, or immunotherapy within 14 days as well as EGFR tyrosine kinase inhibitor within 6 days prior to first dose of study drug.
• Subject has any of the following within 14 days prior to the first dose of study drug:
• Major surgical procedure (other than study related biopsy), or a major surgical procedure is planned to occur during the planned study duration
• Blood transfusions or hemopoietic factor therapy
• Evidence of active infection requiring systemic therapy
• Subject has symptomatic central nervous system (CNS) metastasis. Subject with previously treated brain or CNS metastases is eligible provided that the subject has recovered from any acute effects of radiotherapy and is not requiring systemic steroids and any whole brain radiation therapy was completed at least 2 weeks prior to study drug administration, or any stereotactic radiosurgery was completed at least 1 week prior to study drug administration.
• Subject has a known history of a positive test for human immunodeficiency infection.
• Subject has a known history of a positive test for hepatitis B surface antigen or hepatitis C antibody.
• Subject has known history of serious hypersensitivity reaction to ASP8273, or any component of the formulation used.
• Subject has severe or uncontrolled systemic diseases including uncontrolled hypertension or active bleeding diatheses.
• Subject has history of drug-induced interstitial lung disease (ILD) or any evidence of active ILD.
• Subject has ongoing cardiac arrhythmia that is Grade ≥ 2 or uncontrolled atrial fibrillation of any grade.
• Subject currently has Class III or IV New York Heart Association congestive heart failure.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (3)

Beverly Hills Cancer Center

Beverly Hills, California, 90211, United States

Location

Renovatio Clinical

The Woodlands, Texas, 77380, United States

Location

US Oncology - Virginia Cancer Specialists, P.C. (VCS)

Fairfax, Virginia, 22031, United States

Location

Related Links

• Link to results on the Astellas Clinical Study Results website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

naquotinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Senior Medical

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2017
• First Posted: March 17, 2017
• Study Start: March 24, 2017
• Primary Completion: May 12, 2017
• Study Completion: June 19, 2017
• Last Updated: November 20, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)