Clinical Trials /

AZD9291 Versus Gefitinib or Erlotinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer

NCT02296125

Description:

To assess the efficacy and safety of AZD9291 versus a standard of care epidermal growth factor receptor tyrosine kinase inhibitor in patients with locally advanced or Metastatic Non Small Cell Lung Cancer

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

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

AZD9291 Versus Gefitinib or <span class="go-doc-concept go-doc-intervention">Erlotinib</span> in Patients With Locally Advanced or Metastatic Non-small Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span>

Title

  • Brief Title: AZD9291 Versus Gefitinib or Erlotinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer
  • Official Title: A Phase III, Double-blind, Randomised Study to Assess the Safety and Efficacy of AZD9291 Versus a Standard of Care Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor as First Line Treatment in Patients With Epidermal Growth Factor Receptor Mutation Positive, Locally Advanced or Metastatic Non Small Cell Lung Cancer
  • Clinical Trial IDs

    NCT ID: NCT02296125

    ORG ID: D5160C00007

    NCI ID: 2014-002694-11

    Trial Conditions

    Locally Advanced or Metastatic EGFR Sensitising Mutation Positive Non Small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    AZD9291 80 mg/40 mg + placebo AZD9291 + placebo Standard of Care
    Placebo Erlotinib 150/100mg Placebo Tarceva 150/100 mg AZD9291 + placebo Standard of Care
    Placebo Gefitinib 250 mg Placebo Iressa 250 mg AZD9291 + placebo Standard of Care
    Erlotinib 150/100 mg Tarceva 150/100 mg Standard of Care + placebo AZD9291
    Gefitinib 250 mg Iressa 250mg Standard of Care + placebo AZD9291
    Placebo AZD9291 80 mg/ 40 mg Standard of Care + placebo AZD9291

    Trial Purpose

    To assess the efficacy and safety of AZD9291 versus a standard of care epidermal growth
    factor receptor tyrosine kinase inhibitor in patients with locally advanced or Metastatic
    Non Small Cell Lung Cancer

    Detailed Description

    This is a Phase III, double-blind, randomised study assessing the efficacy and safety of
    AZD9291 (80 mg orally, once daily) versus a standard of care (SoC) Epidermal Growth Factor
    Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) (either gefitinib [250 mg orally, once
    daily] or erlotinib [150 mg orally, once daily]) in patients with locally advanced or
    metastatic Non-small Cell Lung Cancer (NSCLC) that is known to be EGFR sensitising mutation
    (EGFRm) positive, treatment-nave and eligible for first-line treatment with an EGFR-TKI.

    Trial Arms

    Name Type Description Interventions
    AZD9291 + placebo Standard of Care Experimental AZD9291 (80 mg or 40 mg orally, once daily) plus placebo Erlotinib (150 mg or 100 mg orally, once daily) or placebo Gefitinib (250 mg orally, once daily), in accordance with the randomisation schedule. AZD9291 80 mg/40 mg + placebo, Placebo Erlotinib 150/100mg, Placebo Gefitinib 250 mg
    Standard of Care + placebo AZD9291 Active Comparator Erlotinib (150 mg or 100 mg orally, once daily) or placebo Gefitinib (250 mg orally, once daily) plus placebo AZD9291 (80 mg or 40 mg orally, once daily), in accordance with the randomisation schedule. Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Standard of Care arm may have the option to receive open-label AZD9291 (crossover to active AZD9291). Erlotinib 150/100 mg, Gefitinib 250 mg, Placebo AZD9291 80 mg/ 40 mg

    Eligibility Criteria

    Inclusion Criteria:

    1. Male or female, aged at least 18 years.

    2. Pathologically confirmed adenocarcinoma of the lung.

    3. Locally advanced or metastatic NSCLC, not amenable to curative surgery or
    radiotherapy.

    4. The tumour harbours one of the 2 common EGFR mutations known to be associated with
    EGFR-TKI sensitivity (Ex19del, L858R).

    5. Mandatory provision of an unstained, archived tumour tissue sample in a quantity
    sufficient to allow for central analysis of EGFR mutation status.

    6. Patients must be treatment-nave for locally advanced or metastatic NSCLC and
    eligible to receive first-line treatment with gefitinib or erlotinib as selected by
    the participating centre. Prior adjuvant and neo-adjuvant therapy is
    permitted(chemotherapy, radiotherapy, investigational agents).

    Exclusion Criteria:

    1. Treatment with any of the following:

    - Prior treatment with any systemic anti-cancer therapy for locally
    advanced/metastatic NSCLC.

    - Prior treatment with an EGFR-TKI.

    - Major surgery within 4 weeks of the first dose of study drug.

    - Radiotherapy treatment to more than 30% of the bone marrow or with a wide field
    of radiation within 4 weeks of the first dose of study drug.

    - Patients currently receiving medications or herbal supplements known to be
    potent inhibitors or inducers of cytochrome P450 (CYP) 3A4.

    - Alternative anti-cancer treatment

    - Treatment with an investigational drug within five half-lives of the compound or
    any of its related material.

    2. Any concurrent and/or other active malignancy that has required systemic treatment
    within 2 years of first dose of study drug.

    3. Spinal cord compression, symptomatic and unstable brain metastases, except for those
    patients who have completed definitive therapy, are not on steroids, have a stable
    neurologic status for at least 2 weeks after completion of the definitive therapy and
    steroids.

    4. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled
    hypertension and active bleeding diatheses; or active infection including hepatitis
    B, hepatitis C and human immunodeficiency virus (HIV).

    5. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to
    swallow the formulated product, or previous significant bowel resection that would
    preclude adequate absorption of AZD9291.

    6. Any of the following cardiac criteria:

    - Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs, using
    the screening clinic ECG machine-derived QTcF value.

    - Any clinically important abnormalities in rhythm, conduction, or morphology of
    resting ECG.

    - Any factors that increase the risk of QTc prolongation or risk of arrhythmic
    events or unexplained sudden death under 40 years of age in first-degree
    relatives or any concomitant medication known to prolong the QT interval.

    7. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required
    steroid treatment, or any evidence of clinically active ILD.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Progression Free Survival (PFS)

    Secondary Outcome Measures

    Objective Response Rate (ORR)

    Progression Free Survival (PFS) in patients with positive (or negative) T790M mutation

    Overall survival (OS)

    Patient Reported Outcome by Therapy Satisfaction (CTSQ-16 Questionnaire)

    Plasma concentrations of AZD9291 and metabolites AZ5104 and AZ7550; and ratio of metabolite to AZD9291

    Patients reported disease-related symptoms and HRQoL by EORTC QLQ-C30

    Duration of Response (DoR)

    Disease Control Rate (DCR)

    Depth of response

    Patients reported disease-related symptoms and HRQoL by EORTC QLQ-LC13

    Trial Keywords

    Advanced Non-Small Cell Lung Cancer; EGFRm+; AZD9291; TKI; Phase III