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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Astellas Pharma Inc
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier:
NCT02113813
First received: April 4, 2014
Last updated: August 27, 2014
Last verified: August 2014
  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 and evaluate the potential inhibition of CYP3A4 by ASP8273 and the antitumor activity of ASP8273.


Condition Intervention Phase
Non-Small-Cell Lung Cancer (NSCLC)
Epidermal Growth Factor Receptor Mutations
Drug: ASP8273
Drug: midazolam
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • Composite of pharmacokinetics of ASP8273 concentration and its metabolites (plasma): Cmax, tmax, AUClast, AUCinf, t1/2, CL/F, and Vz/F [ Time Frame: Day 1 of Cycles 0-3, Day 8 and 15 of Cycle 1 ] [ 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, Day 1 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.


Estimated Enrollment: 65
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)
Arms Assigned Interventions
Experimental: ASP8273 Dose Escalation cohort (part 1) Drug: ASP8273
oral
Experimental: ASP8273 Response Expansion cohort (part 1) Drug: ASP8273
oral
Experimental: ASP8273 and Midazolam RP2D Expansion cohort (part 2) Drug: ASP8273
oral
Drug: midazolam
oral

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 L861Q; and received prior treatment with EGFR Tyrosine Kinase Inhibitor (TKI)
  • Response expansion/RP2D expansion subjects: disease progression on prior EGFR TKI; no anticancer treatment subsequent to 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 reversible EGFR inhibitor within 7 days; irreversible EGFR inhibitor or any antitumor agent within 14 days; any investigational therapy within 28 days; blood transfusion or hemopoietic factor within 14 days; major surgery within 14 days; any strong CYP3A4 inhibitors within 7 days
  • Expansion cohorts only - subject has had prior treatment with an EGFR-T790M inhibitor (CO-1686, AZD9291)
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02113813

Contacts
Contact: Astellas Pharma Global Development 800-888-7704 ext 5473 clintrials.info@us.astellas.com

Locations
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, 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, 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
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Investigators
Study Director: Executive Medical Director Astellas Pharma Global Development, Inc.
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier: NCT02113813     History of Changes
Other Study ID Numbers: 8273-CL-0102
Study First Received: April 4, 2014
Last Updated: August 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Astellas Pharma Inc:
Non-Small-Cell Lung Cancer
NSCLC
Epidermal Growth Factor Receptor mutations
EGFR
ASP8273
Midazolam
irreversible EGFR inhibitor
T790M resistance mutation

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Midazolam
Mitogens
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Mitosis Modulators

ClinicalTrials.gov processed this record on September 11, 2014