Clinical Trials /

A Dose Escalation Study of ASP8273 in Subjects With Non-Small-Cell Lung Cancer (NSCLC) Who Have Epidermal Growth Factor Receptor (EGFR) Mutations

NCT02113813

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

A Dose Escalation Study of ASP8273 in Subjects With Non-Small-Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span> (NSCLC) Who Have Epidermal Growth Factor Receptor (<span class="go-doc-concept go-doc-biomarker">EGFR</span>) <span class="go-doc-concept go-doc-keyword">Mutations</span>

Title

  • Brief Title: A Dose Escalation Study of ASP8273 in Subjects With Non-Small-Cell Lung Cancer (NSCLC) Who Have Epidermal Growth Factor Receptor (EGFR) Mutations
  • 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
  • Clinical Trial IDs

    NCT ID: NCT02113813

    ORG ID: 8273-CL-0102

    Trial Conditions

    Non-Small-Cell Lung Cancer (NSCLC)

    Epidermal Growth Factor Receptor Mutations

    Trial Interventions

    Drug Synonyms Arms
    ASP8273 ASP8273 Dose Escalation cohort (part 1), ASP8273 Response Expansion cohort (part 1), ASP8273 and Midazolam RP2D Expansion cohort (part 2), Food Effect Fasted cohort (part 2), Food Effect Fed cohort (part 2)
    midazolam ASP8273 and Midazolam RP2D Expansion cohort (part 2)

    Trial Purpose

    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.

    Detailed Description

    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.

    Trial Arms

    Name Type Description Interventions
    ASP8273 Dose Escalation cohort (part 1) Experimental ASP8273
    ASP8273 Response Expansion cohort (part 1) Experimental ASP8273
    ASP8273 and Midazolam RP2D Expansion cohort (part 2) Experimental ASP8273, midazolam
    Food Effect Fasted cohort (part 2) Experimental ASP8273
    Food Effect Fed cohort (part 2) Experimental ASP8273

    Eligibility Criteria

    Inclusion Criteria:

    - Non-child bearing potential or able to follow birth control requirements

    - Eastern Cooperative Oncology Group (ECOG) 1

    - Life expectancy 12 weeks

    - Laboratory criteria as:

    - Neutrophil count 1,500/mm3

    - Platelet count 7.5 x 104 /mm3

    - Hemoglobin 9.0 g/dL

    - Lymphocyte count 500/mm3

    - Serum creatinine < 1.5 x institutional Upper Limit of Normal (ULN) or an
    estimated glomerular filtration rate (eGFR) of > 50 ml/min as calculated by the
    Modification of Diet in Renal Disease (MDRD) equation

    - Total bilirubin < 1.5 x ULN (except for subjects with documented Gilbert's
    syndrome)

    - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.0 x ULN

    - Dose escalation subjects: Epidermal Growth Factor Receptor (EGFR) activating mutation
    by local testing: exon 18 G719X, exon 19 deletion, exon 21 L861Q, exon 21 L858R or
    exon 20 insertion; and received prior treatment with EGFR Tyrosine Kinase Inhibitor
    (TKI)

    - Response expansion/RP2D expansion/ FE Cohort subjects: disease progression on or was
    intolerant to prior EGFR TKI; activating mutation as above AND T790M mutation; tumor
    sample subsequent to EGFR TKI is available for central testing; at least one
    measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

    Exclusion Criteria:

    - Any ongoing toxicity Grade 2 attributable to prior Non-Small-Cell Lung Cancer
    (NSCLC) treatment

    - Prior EGFR inhibitor within 6 days; received prior treatment with any other agent
    with antitumor activity chemotherapy, radiotherapy, or immunotherapy within 14 days;
    any investigational therapy within 28 days or 5 half-lives, whichever is shorter;
    blood transfusion or hemopoietic factor within 14 days; major surgery within 14 days;
    any strong CYP3A4 inhibitors within 7 days

    - Positive hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) or
    Human Immunodeficiency Virus (HIV)

    - Symptomatic Central Nervous System (CNS) metastasis

    - Active infection requiring systemic therapy within 14 days

    - Severe or uncontrolled systemic diseases including uncontrolled hypertension

    - History of or active interstitial lung disease

    - Screening QTcF >450 msec or current medication known to prolong QT

    - Grade 2 cardiac arrhythmia or uncontrolled atrial fib of any grade; Class 3 or 4
    New York Heart Association congestive heart failure; history of severe/unstable
    angina, myocardial infarction or cerebrovascular accident within 6 months

    - History of gastrointestinal ulcer or bleeding within 3 months; any digestive tract
    dysfunction

    - Concurrent corneal disorder or ophthalmologic condition making subject unsuitable

    - RP2D cohort subjects: contraindications to midazolam, any other midazolam within 7
    days, or any medications or supplements known to be strong CYP3A inhibitors within 7
    days or inducers within 12 days

    - Any other malignancy requiring treatment

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Safety and tolerability as assessed by Dose Limiting Toxicities (DLTs)

    Safety and tolerability as assessed by adverse events (AEs)

    Safety and tolerability as assessed by laboratory tests

    Safety and tolerability as assessed by vital signs

    Safety and tolerability as assessed by 12-lead electrocardiograms (ECGs)

    Secondary Outcome Measures

    Composite of pharmacokinetics of ASP8273 concentration and its metabolites (plasma): Cmax, tmax, AUClast, AUCinf, t1/2, CL/F, and Vz/F

    Composite of pharmacokinetics of midazolam concentration and its metabolites (plasma): Cmax, tmax, AUClast, AUCinf, t1/2, CL/F, and Vz/F

    Best overall response rate

    Disease control rate

    Progression free survival

    Trial Keywords

    Non-Small-Cell Lung Cancer

    NSCLC

    Epidermal Growth Factor Receptor mutations

    EGFR

    ASP8273

    Midazolam

    irreversible EGFR inhibitor

    T790M resistance mutation