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A Study of ASP8273 vs. Erlotinib or Gefitinib in First-line Treatment of Patients With Stage IIIB/IV Non-small Cell Lung Cancer Tumors With EGFR Activating Mutations

NCT02588261

Description:

The purpose of the study was to evaluate the progression free survival (PFS), based on independent radiologic review (IRR), of ASP8273 compared to erlotinib or gefitinib in patients with locally advanced, metastatic or unresectable stage IIIB/IV adenocarcinoma non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) activating mutations. This study also assessed Overall survival (OS); Overall response rate (ORR) as assessed by IRR; PFS as assessed by the investigator; Disease control rate (DCR) as assessed by IRR; Duration of Response (DOR) by IRR; Safety of ASP8273; and Quality of Life (QOL) and patient-reported outcome (PRO) parameters.

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

Terminated

Phase:

Phase 3

Trial Eligibility

Document

A Study of ASP8273 vs. Erlotinib or Gefitinib in First-line Treatment of Patients With Stage IIIB/IV Non-small Cell Lung Cancer Tumors With <span class="go-doc-concept go-doc-biomarker">EGFR</span> Activating <span class="go-doc-concept go-doc-keyword">Mutations</span>

Title

  • Brief Title: A Study of ASP8273 vs. Erlotinib or Gefitinib in First-line Treatment of Patients With Stage IIIB/IV Non-small Cell Lung Cancer Tumors With EGFR Activating Mutations
  • Official Title: An Open-label, Randomized Phase 3 Efficacy Study of ASP8273 vs Erlotinib or Gefitinib in First-line Treatment of Patients With Stage IIIB/IV Non-small Cell Lung Cancer Tumors With EGFR Activating Mutations
  • Clinical Trial IDs

    NCT ID: NCT02588261

    ORG ID: 8273-CL-0302

    NCI ID: 2015-002894-39

    Trial Conditions

    Non-small Cell Lung Cancer (NSCLC)

    Trial Interventions

    Drug Synonyms Arms
    ASP8273 ASP8273
    Erlotinib OSI-774, Tarceva erlotinib/gefitinib
    Gefitinib erlotinib/gefitinib

    Trial Purpose

    The purpose of the study is to evaluate the progression free survival (PFS), based on
    independent radiologic review (IRR), of ASP8273 compared to erlotinib or gefitinib in
    patients with locally advanced, metastatic or unresectable stage IIIB/IV adenocarcinoma
    non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) activating
    mutations.

    This study will also assess Overall survival (OS); Overall response rate (ORR) as assessed
    by IRR; PFS as assessed by the investigator; Disease control rate (DCR) as assessed by IRR;
    and Safety of ASP8273.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    ASP8273 Experimental Patients randomized to this arm will receive a daily dose of ASP8273 ASP8273
    erlotinib/gefitinib Active Comparator Patients randomized to this arm will receive a daily dose of either erlotinib or gefitinib Erlotinib, Gefitinib

    Eligibility Criteria

    Inclusion Criteria:

    - Subject agrees not to participate in another interventional study while on treatment.

    - 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

    - 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 serum pregnancy test at Screening; And, if heterosexually active, agree
    to consistently use 2 forms of highly effective birth control (at least 1 of
    which must be a barrier method) starting at Screening and throughout the study
    period and for 28 days after the final study drug administration.

    - Female subject must not be breastfeeding at Screening or during 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.

    - Male subject and their female spouse/partners who are of childbearing potential must
    be using highly effective contraception consisting of 2 forms of birth control (1 of
    which must be a barrier method) starting at Screening and continue 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 has Eastern Cooperative Oncology Group (ECOG) performance status 2.

    - Subject has histologically confirmed locally advanced, metastatic or unresectable
    Stage IIIB/IV adenocarcinoma NSCLC (newly diagnosed or recurrent). Subjects with
    mixed histology are eligible if adenocarcinoma is the predominant histology.

    - Subject has predicted life expectancy 12 weeks in the opinion of the investigator.

    - Subject must meet all of the following criteria on the laboratory tests that will be
    analyzed centrally within 7 days prior to the first dose of study drug. In case of
    multiple laboratory data within this period, the most recent data should be used.

    - Neutrophil count > 1,000/mm3

    - Platelet count 7.5 x 104 /mm3

    - Hemoglobin > 8.0 g/dL

    - Serum creatinine 2.0 x upper limit of normal (ULN) or an estimated glomerular
    filtration rate (eGFR) of > 50 mL/min as calculated by the Cockcroft Gault
    Method

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

    - AST and ALT 3.0 x ULN or 5 x ULN if subject has documented liver metastases

    - Serum sodium level is 130 mmol/L

    - Subject has an EGFR activating mutation (exon 19 deletion or exon 21 L858R), with or
    without T790M mutation, by local or central testing on examination of a NSCLC FFPE
    specimen. A tissue sample from the same block used to determine eligibility by local
    testing should be available to send to the central lab for confirmatory testing.

    - Subject must have at least 1 measureable lesion based on RECIST V1.1.

    Exclusion Criteria:

    - Subject has received intervening anticancer treatment or previous treatment with
    chemotherapy for metastatic disease. The administration of neoadjuvant or adjuvant
    chemotherapy is allowed as long as it has finalized 6 months before the first dose
    of study drug.

    - Subject has received a prior treatment with a therapeutic agent targeting EGFR (e.g.,
    afatinib, dacomitinib, ASP8273, etc).

    - Subject has received investigational therapy within 28 days or 5 half-lives prior to
    the first dose of study drug.

    - Subject has received radiotherapy within 1 week prior to the first dose of study
    drug. If the subject received radiotherapy > 1 week prior to study treatment, the
    irradiated lesion cannot be the only lesion used for evaluating response.

    - Subject has symptomatic central nervous system (CNS) metastasis. Subject with
    previously treated brain or CNS metastases are eligible provided that the subject has
    recovered from any acute effects of radiotherapy and is not requiring escalating
    doses of steroids, and any whole brain radiation therapy was completed at least 2
    weeks prior to study drug administration, or any stereotactic radiosurgery (SRS) was
    completed at least 1 week prior to the first dose of study drug.

    - Subject has received blood transfusions or hematopoietic factor therapy within 14
    days prior to the first dose of study drug.

    - Subject has had a major surgical procedure (other than a biopsy) within 14 days prior
    to the first dose of study drug, or one is planned during the course of the study.

    - Subject has a known history of a positive test for human immunodeficiency virus (HIV)
    infection.

    - Subject has known history of serious hypersensitivity reaction to a known ingredient
    of ASP8273, erlotinib or gefitinib.

    - Subject has evidence of an active infection requiring systemic therapy within 14 days
    prior to the planned first dose of study drug.

    - Subject has severe or uncontrolled systemic diseases including uncontrolled
    hypertension (blood pressure > 150/100 mmHg) 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 3 or 4 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 history of 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 which, in the
    investigator's opinion, makes the subject unsuitable for study participation (i.e.,
    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 malignancy which requires treatment.

    - Subject has any condition which, in the investigator's opinion, makes the subject
    unsuitable for study participation.

    - Subject has used the following drugs:

    - Potent CYP 3A4 inhibitors within 7 days prior to first dose of study drug

    - Proton pump inhibitors such as omeprazole within 14 days prior to first dose of
    study drug

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Progression Free Survival (PFS) as assessed by Independent Radiologic Review (IRR)

    Secondary Outcome Measures

    Overall Survival (OS)

    Best Overall Response Rate (ORR) as assessed by IRR

    PFS as assessed by the investigator

    Disease Control Rate (DCR) as assessed by IRR

    Safety profile assessed by adverse events, laboratory tests, vital signs and electrocardiograms (ECG

    Trial Keywords

    Non-small cell lung cancer (NSCLC)

    ASP8273

    erlotinib

    gefitinib

    EGFR mutation