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Non-small Cell Lung Cancer (NSCLC)Phase 1NCT03082300

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

A Phase 1 study testing naquotinib in people with Non-small Cell Lung Cancer (NSCLC) and Epidermal Growth Factor Receptor (EGFR) Mutations, run by Astellas Pharma Global Development, Inc. at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
naquotinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
3 sitesUnited States
Study dates
24 Mar 2017to 19 Jun 2017
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

  • 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
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  • 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:
  • Postmenopausal (defined as at least 1 year without any menses) prior to screening, or
  • Documented surgically sterile (e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy) Or, if of childbearing potential,
  • Agree not to try to become pregnant during the study and for 28 days after the final study drug administration
  • And have a negative blood pregnancy test at the time of screening
  • And if heterosexually active, agrees to consistently use 1 form of highly effective birth control* starting at screening and throughout the study period and for 28 days after the final study drug administration.
  • Female subject must agree not to breastfeed at screening and throughout the study period, and for 28 days after the final study drug administration.
  • Female subject must not donate ova starting at screening and throughout the study period, and for 28 days after the final study drug administration.
  • A sexually active male subject with female partner(s) who are of childbearing potential is eligible if:
  • Agrees to use a male condom starting at screening and continue throughout study treatment and for 90 days after the final study drug administration. If the male subject has not had a vasectomy or is not sterile as defined below their female partner(s) is utilizing 1 form of highly effective birth control*starting at screening and continue throughout study treatment and for 90 days after the male subject receives their final study drug administration.
  • Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 90 days after the final study drug administration
  • Male subject must not donate sperm starting at screening and throughout the study period, and for 90 days after the final study drug administration.
  • Subject must be willing to fast for approximately 10 hours predose and 4 hours postdose on day 1 of each period in the pharmacokinetic phase.
  • Highly effective forms of birth control include:
  • Consistent and correct usage of established hormonal contraceptives that inhibit ovulation,
  • Established intrauterine device or intrauterine system.
  • Vasectomy (A vasectomy is a highly effective contraception method provided the absence of sperm has been confirmed. If not, an additional highly effective method of contraception should be used).
  • Male subject is sterile due to a bilateral orchiectomy.

Who cannot join

  • 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
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  • 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.
  • Subject has history of severe/unstable angina, myocardial infarction or cerebrovascular accident within 6 months prior to the planned first dose of study drug.
  • Subject has active gastrointestinal ulcer or gastrointestinal bleeding within 3 months prior to the planned first dose of study drug.
  • Subject has concurrent corneal disorder or any ophthalmologic condition that makes the subject unsuitable for study participation (e.g., advanced cataracts, glaucoma).
  • Subject has difficulty taking oral medication or any digestive tract dysfunction or inflammatory bowel disease that would interfere with the intestinal absorption of drug.
  • Subject has another past or active malignancy that requires treatment. Prior carcinoma in situ and/or nonmelanoma skin cancer after curative resection are permitted.
  • Subject has received the following within 14 days prior to the first dose of study drug:
  • Strong or moderate CYP3A4 inhibitors or inducers
  • Strong or moderate P-gp inhibitors or inducers

Trial locations and contacts

3 sites in 1 country.

United States3 sites
  • Beverly Hills Cancer Center

    Beverly Hills, California, 90211

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

    Fairfax, Virginia, 22031

  • Renovatio Clinical

    The Woodlands, Texas, 77380

Other trials in United States

About this study

Official title: A Phase 1, Randomized, 2-period Crossover Study to Assess Bioequivalence of a Tablet Formulation Versus a Capsule Formulation of ASP8273 in Subjects With Non-small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutations

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.

Read the detailed description

Study and subjects will be divided into two phases: a pharmacokinetic (PK) and a postpharmacokinetic phase. The pharmacokinetic phase will follow a randomized, 2 period, 2 sequence single dose crossover design. Each period will be 5 days in duration. Within the sequence, both an ASP8273 tablet and ASP8273 capsule will be administered under fasted condition. The postpharmacokinetic phase will consist of up to 1 cycle (28 days) of continuous once daily dosing in post PK phase with ASP8273 capsules. Dose modifications are allowed if necessary in post PK phase and they follow a step-wise dose reduction. Subject is able to re-escalate dose level if reaction is stable.

Being tested
naquotinib
Keywords
ASP8273, Epidermal growth factor receptor (EGFR) mutations, naquotinib, Non-small cell lung cancer (NSCLC), Bioequivalence
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

Study groups in NCT03082300
Study groupRoleWhat they receive
Pharmacokinetic phase: ASP8273 Tablet then Capsule SequenceExperimentalSubjects 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
Receives: Drug: naquotinib
Pharmacokinetic phase: ASP8273 Capsule then Tablet SequenceExperimentalSubjects 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
Receives: Drug: naquotinib
Postpharmacokinetic phase: ASP8273 Capsule FormulationExperimentalAll subjects will receive ASP8273 capsules in once-daily dosing for 1 cycle (28 days)
Receives: Drug: naquotinib

What is being measured

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

  1. Pharmacokinetics of ASP8273 in plasma: Cmax

    Cmax: Maximum plasma concentration. Pharmacokinetic phase only

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

  2. Pharmacokinetics of ASP8273 in plasma: AUCinf

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

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

  3. Pharmacokinetics of ASP8273 in plasma: AUClast

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

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

  4. Pharmacokinetics of ASP8273 in plasma: AUC72

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

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

Secondary outcomes (9)
  1. Pharmacokinetics of ASP8273 in plasma: t1/2

    t1/2: Terminal elimination half-life. Pharmacokinetic phase only

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

  2. Pharmacokinetics of ASP8273 in plasma: tmax

    tmax: The time of maximum concentration. Pharmacokinetic phase only

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

  3. Pharmacokinetics of ASP8273 in plasma: tlast

    tlast: The time of last observed concentration. Pharmacokinetic phase only

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

  4. Pharmacokinetics of ASP8273 in plasma: CL/F

    CL/F: Oral clearance. Pharmacokinetic phase only

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

  5. Pharmacokinetics of ASP8273 in plasma: Vz/F

    Vz/F: Apparent volume of distribution. Pharmacokinetic phase only

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

  6. Safety and tolerability assessed by nature, frequency, and severity of adverse events (AES)

    For both pharmacokinetic and postpharmacokinetic phases

    Measured: Up to day 30

  7. Number of participants with vital sign abnormalities and/or adverse events related to treatment

    Vital signs include systolic and blood diastolic pressure, temperature and pulse rate. For both pharmacokinetic and postpharmacokinetic phases

    Measured: Up to day 30

  8. Number of participants with laboratory abnormalities and/or adverse events related to treatment

    Laboratory values include biochemical, hematological, coagulation and urine analysis. For both pharmacokinetic and postpharmacokinetic phases

    Measured: Up to day 30

  9. Safety assessed by routine 12-lead electrocardiograms (ECG)

    Routine 12-lead ECGs will be performed after the subject has been in a supine position for at least 5 minutes. For both pharmacokinetic and postpharmacokinetic phases

    Measured: Up to day 30

Timeline

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

  1. First posted17 Mar 2017
  2. Study start24 Mar 2017
  3. Primary completion12 May 2017
  4. Study completion19 Jun 2017

Why it stopped: Following recommendation by SOLAR Study IDMC, Astellas closed enrollment in ASP8273 studies.

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
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03082300
Sponsor's protocol ID
8273-CL-0112
Status last verified
Nov 2024
First submitted
13 Mar 2017
Last updated
20 Nov 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: 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/.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing naquotinib in people with Non-small Cell Lung Cancer (NSCLC) and Epidermal Growth Factor Receptor (EGFR) Mutations, run by Astellas Pharma Global Development, Inc. at 3 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 32 inclusion and 23 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: stopped early, as of the sponsor's last update on 20 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 3 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 was stopped early (reason given: Following recommendation by SOLAR Study IDMC, Astellas closed enrollment in ASP8273 studies.). Results are not available in the source record.

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?

Pharmacokinetics of ASP8273 in plasma: Cmax (time frame: Up to Day 5 in each period of Phase 1 (maximum of 10 days)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 20 Nov 2024.

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