Clinical Trials /

Real World Treatment Study of AZD9291 for Advanced/Metastatic EGFR T790M Mutation NSCLC

NCT02474355

Description:

The aim of this study is to assess the efficacy and safety of single agent AZD9291 in a real world setting in adult patients with advanced or metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive Non-Small Cell Lung Cancer (NSCLC), who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy.

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

Completed

Phase:

Phase 3

Trial Eligibility

Document

Real World Treatment Study of AZD9291 for Advanced/Metastatic <span class="go-doc-concept go-doc-alteration">EGFR T790M</span> <span class="go-doc-concept go-doc-keyword">Mutation</span> <span class="go-doc-concept go-doc-disease">NSCLC</span>

Title

  • Brief Title: Real World Treatment Study of AZD9291 for Advanced/Metastatic EGFR T790M Mutation NSCLC
  • Official Title: Open Label, Multinational, Multicenter, Real World Treatment Study of Single Agent AZD9291 for Patients With Advanced/Metastatic Epidermal Growth Factor Receptor (EGFR) T790M Mutation-Positive Non-Small Cell Lung Cancer (NSCLC) Who Have Received Prior Therapy With an EGFR Tyrosine Kinase Inhibitor (EGFR-TKI)
  • Clinical Trial IDs

    NCT ID: NCT02474355

    ORG ID: D5160C00022

    Trial Conditions

    Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    AZD9291 Dosing AZD9291

    Trial Purpose

    The aim of this study is to assess the efficacy and safety of single agent AZD9291 in a real
    world setting in adult patients with advanced or metastatic, epidermal growth factor
    receptor (EGFR) T790M mutation-positive Non-Small Cell Lung Cancer (NSCLC), who have
    received prior EGFR-tyrosine kinase inhibitor (TKI) therapy.

    Detailed Description

    Objective: The primary objective of this study is to assess the efficacy and safety of
    single agent AZD9291 in a real world setting in adult patients with advanced or metastatic,
    epidermal growth factor receptor (EGFR) T790M mutation-positive Non-Small Cell Lung Cancer
    (NSCLC), who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy.

    Study site(s) and number of patients planned: Approximately 1500 patients will be recruited
    in Europe. The recruitment will be increased beyond that as the study will expand in other
    regions of the world (America, Asia).

    Study Design This will be an open-label, single-arm, multinational, multicenter, real world
    treatment study.

    Target patient population: Adult patients (fulfilling the definition of "age of majority"
    per local regulations) with locally advanced (stage IIIB) or metastatic (stage IV) NSCLC
    with confirmed T790M mutation, who have received prior EGFR-TKI therapy.

    Investigational product (IP), dosage, and mode of administration: AZD9291 is an oral,
    potent, selective, irreversible inhibitor of both EGFR-TKI sensitising and resistance
    mutations in NSCLC with a significant selectivity margin over wild-type EGFR. AZD9291 will
    be administered orally as one 80 mg tablet once a day.

    Duration of IP administration: Patients may continue to receive AZD9291 as long as they
    continue to show clinical benefit, as judged by the investigator, and in the absence of
    discontinuation criteria). The study will be closed in each participating country as soon as
    possible following national reimbursement of AZD9291 in that country (up to a max of 90 days
    post reimbursement). Enrolment will be closed within 6 months after market license approval
    in that country or at national reimbursement, whichever is sooner. Patients withdrawing from
    the treatment prior to national reimbursement will be followed up as part of this study.
    Patients on treatment will receive commercial supply until documented disease progression as
    per investigator assessment.

    In the event that national reimbursement should not be granted following a reasonable time
    after market license approval in the country, the study will be closed in a maximum period
    of 18 months after the last patient is enrolled in that country. If applicable, timelines
    for conversion to commercial drug will be agreed with local bodies which may include
    regulatory agencies, ethics committees, and institutions. Patient will be followed until
    death or lost to follow-up.

    Study measures: Data collected will include patient demographics, information needed to
    determine patient eligibility (including medical history, past and current disease
    characteristics, and tumor EGFR mutational status), AZD9291 exposure, investigator-reported
    efficacy (including tumor response and disease progression), overall survival (OS), and
    safety (including serious adverse events [SAEs], adverse events leading to dose
    modification, and adverse events of special interest [interstitial lung
    disease/pneumonitis-like events, and QTc prolongation events]).

    Statistical methods: All data will be presented for the overall full analysis/evaluable set,
    and also by cohorts defined by number and type of previous treatment lines for the advanced
    disease. Descriptive statistics will be used for all variables, as appropriate. Continuous
    variables will be summarised by the number of observations, mean, standard deviation,
    median, minimum, and maximum. Categorical variables will be summarised by frequency counts
    and percentages for each category. OS and PFS will be summarized using Kaplan-Meier
    estimates of the median time to death or censoring and quartiles together with their 95%
    confidence intervals.

    Trial Arms

    Name Type Description Interventions
    AZD9291 Experimental Single arm of AZD9291, starting dose of 80mg AZD9291 Dosing

    Eligibility Criteria

    Inclusion Criteria:

    1. Provision of signed and dated written informed consent by the patient or legally
    acceptable representative prior to any study-specific procedures

    2. Adults (according to each country regulations for age of majority)

    3. Locally advanced (stage IIIB) or metastatic (stage IV) EGFRm NSCLC, not amenable to
    curative surgery or radiotherapy, with confirmation of the presence of the T790M
    mutation

    4. Prior therapy with an EGFR-TKI. Patients may have also received additional lines of
    treatment

    5. World Health Organization (WHO) performance status 0-2

    6. Adequate bone marrow reserve and organ function as demonstrated by complete blood
    count, biochemistry in blood and urine at baseline (please refer to IB for guidance)

    7. ECG recording at baseline showing absence of any cardiac abnormality as per exclusion
    criterion #6

    8. Female patients of childbearing potential must be using adequate contraceptive
    measures, must not be breast feeding, and must have a negative pregnancy test prior
    to start of dosing. Otherwise, they must have evidence of nonchildbearing potential

    9. Male patients must be willing to use barrier contraception, i.e., condoms

    Exclusion Criteria:

    1. Previous (within 6 months) or current treatment with AZD9291

    2. Patients currently receiving (or unable to stop use at least 1 week prior to
    receiving the first dose of AZD9291) any treatment known to be potent inhibitors or
    inducers of cytochrome P450 (CYP) 3A4

    3. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled
    hypertension, active bleeding diatheses, active infection including hepatitis B,
    hepatitis C, and human immunodeficiency virus, or significantly impaired bone marrow
    reserve or organ function, including hepatic and renal impairment, which in the
    investigator's opinion would significantly alter the risk/benefit balance.

    4. Patient with symptomatic central nervous system (CNS) metastases who is
    neurologically unstable or has required increasing doses of steroids to manage CNS
    symptoms within the 2 weeks prior to start AZD9291 administration;

    5. Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring
    steroid treatment, or any evidence of clinically active ILD

    6. Any of the following cardiac criteria:

    1. Mean resting corrected QT interval (QTcF) > 470 ms using Fredericia's formula :

    2. Any clinically important abnormalities in rhythm, conduction or morphology of
    resting ECG (e.g., complete left bundle branch block, third degree heart block,
    second degree heart block)

    3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic
    events

    7. Any unresolved toxicity from prior therapy CTCAE > grade 3 at the time of starting
    treatment

    8. History of hypersensitivity to excipients of AZD9291 or to drugs with a similar
    chemical structure or class to AZD9291

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Efficacy of AZD9291 by the analysis of overall survival.

    Safety of AZD9291 by assessment of Serious Adverse Events, Adverse Events of special interest (Interstitial Lung Disease/pneumonitis-like events, Cardiac events)

    Secondary Outcome Measures

    Efficacy of AZD9291 by the analysis of Progression Free Survival (PFS)

    Trial Keywords

    NSCLC

    EGFRm

    T790M