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Non-Small-Cell Lung Cancer (NSCLC)Phase 1NCT02113813

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

A Phase 1 study testing naquotinib and midazolam in people with Non-Small-Cell Lung Cancer (NSCLC) and Epidermal Growth Factor Receptor Mutations, run by Astellas Pharma Global Development, Inc. at 12 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
naquotinib and midazolam
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
133 participants
Where
12 sitesUnited States
Study dates
9 Apr 2014to 11 Feb 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Subject on any line of treatment and has an EGFR exon 20 insertion mutation on examination of an NSCLC tissue or cellular specimen. Local testing may determine eligibility and a tumor sample should also be sent for central testing.
  • Subjects must have at least 1 measurable lesion based on RECIST version 1.1.

Who cannot join

  • 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
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  • 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

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites

  • Site US10006

    Baltimore, Maryland, 21231

  • Site US10012

    Boston, Massachusetts, 02114

  • Site US10001

    Boston, Massachusetts, 02215

  • Site US10011

    Boston, Massachusetts, 02215

  • Site US10004

    Chapel Hill, North Carolina, 27599

  • Site US10005

    Cleveland, Ohio, 44106

  • Site US10003

    Fairfax, Virginia, 22031

  • Site US10002

    Nashville, Tennessee, 37232

  • Site US10008

    New York, New York, 10065

  • Site US10009

    Philadelphia, Pennsylvania, 19104

  • Site US10007

    Seattle, Washington, 98104

  • Site US10010

    Washington D.C., District of Columbia, 20007-2113

Other trials in United States

About this study

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

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.

Read the 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, Food Effect (FE) cohort and Exon 20 cohort.

Being tested
naquotinib, midazolam
Keywords
irreversible EGFR inhibitor, Non-Small-Cell Lung Cancer, Midazolam, T790M resistance mutation, EGFR, NSCLC, naquotinib, Epidermal Growth Factor Receptor mutations, ASP8273
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • naquotinibDrug

    Also called ASP8273

    oral

  • midazolamDrug

    oral

Study groups in NCT02113813
Study groupRoleWhat they receive
ASP8273 Dose Escalation cohort (part 1)Experimentaloral
Receives: Drug: naquotinib
ASP8273 Response Expansion cohort (part 1)Experimentaloral
Receives: Drug: naquotinib
ASP8273 and Midazolam RP2D Expansion cohort (part 2)Experimentaloral
Receives: Drug: naquotinib; Drug: midazolam
Food Effect Fasted cohort (part 2)Experimentaloral
Receives: Drug: naquotinib
Food Effect Fed cohort (part 2)Experimentaloral
Receives: Drug: naquotinib
Exon 20 Cohort (part 2)Experimentaloral
Receives: Drug: naquotinib

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    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.

    Measured: up to 18 months

  2. Safety and tolerability as assessed by adverse events (AEs)

    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.

    Measured: up to 18 months

  3. Safety and tolerability as assessed by laboratory tests

    Laboratory tests to be conducted are hematology, biochemistry, urinalysis, coagulation profile, lipid panel and lymphocyte subpopulation.

    Measured: up to 18 months

  4. Safety and tolerability as assessed by vital signs

    Vital signs to be measured includes blood pressure, pulse rate and temperature.

    Measured: up to 18 months

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

    Measured: up to 18 months

Secondary outcomes (5)

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

    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)

    Measured: Cycle 0: Dose Escalation Days 1-2, FE Days 1-6; Cycle 1: Dose Escalation/Response Expansion/RP2D/FE Days 1,8,15, RP2D Day 21, Exon 20 Days 8,15; Cycle 2 & 3: Dose Escalation/Response Expansion/RP2D Days 1,2, FE Day 1; Exon 20 days 1, 2 & Cycle 3

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

    Measured: Day -1 and Day 1 of cycle 1; Day 1 and Day 2 of cycle 2

  3. Best overall response rate

    Defined as proportion of subjects whose best overall response is Complete Response (CR) or Partial Response (PR) among all analyzed subjects.

    Measured: Up to 18 months

  4. Disease control rate

    Defined as the proportion of subjects whose best overall response is rated as CR, PR or Stable Disease (SD) among all analyzed subjects.

    Measured: Up to 18 months

  5. Progression free survival

    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.

    Measured: Up to 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Apr 2014 (estimated)
  2. Study start9 Apr 2014
  3. Primary completion28 Jul 2017
  4. Study completion11 Feb 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
133 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02113813
Sponsor's protocol ID
8273-CL-0102
Status last verified
Nov 2024
First submitted
4 Apr 2014
Last updated
14 Nov 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing naquotinib and midazolam in people with Non-Small-Cell Lung Cancer (NSCLC) and Epidermal Growth Factor Receptor Mutations, run by Astellas Pharma Global Development, Inc. at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and tolerability as assessed by Dose Limiting Toxicities (DLTs) (time frame: up to 18 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02113813.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2024.

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