Clinical Trials /

AZD9291 Versus Placebo in Patients With Stage IB-IIIA Non-small Cell Lung Carcinoma, Following Complete Tumour Resection With or Without Adjuvant Chemotherapy.

NCT02511106

Description:

To assess the efficacy and safety of AZD9291 versus Placebo, in patients with Epidermal Growth Factor Receptor Mutation Positive stage IB-IIIA non-small cell lung carcinoma, following complete tumour resection with or without adjuvant chemotherapy

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

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

AZD9291 Versus <span class="go-doc-concept go-doc-intervention">Placebo</span> in Patients With Stage IB-IIIA Non-small Cell Lung Carcinoma, Following Complete Tumour Resection With or Without <span class="go-doc-concept go-doc-intervention">Adjuvant Chemotherapy</span>

Title

  • Brief Title: AZD9291 Versus Placebo in Patients With Stage IB-IIIA Non-small Cell Lung Carcinoma, Following Complete Tumour Resection With or Without Adjuvant Chemotherapy
  • Official Title: A Phase III, Double-blind, Randomized, Placebo-controlled Multi-centre, Study to Assess the Efficacy and Safety of AZD9291 Versus Placebo, in Patients With Epidermal Growth Factor Receptor Mutation Positive Stage IB-IIIA Non-small Cell Lung Carcinoma, Following Complete Tumour Resection With or Without Adjuvant Chemotherapy (ADAURA)
  • Clinical Trial IDs

    NCT ID: NCT02511106

    ORG ID: D5164C00001

    NCI ID: 2015-000662-65

    Trial Conditions

    Stage IB-IIIA Non-small Cell Lung Carcinoma, With a Centrally Confirmed, Common Sensitising EGFR Mutations

    Trial Interventions

    Drug Synonyms Arms
    AZD9291 80 mg/40 mg AZD9291
    Placebo AZD9291 80 mg/40 mg Placebo AZD9291

    Trial Purpose

    To assess the efficacy and safety of AZD9291 versus Placebo, in patients with Epidermal
    Growth Factor Receptor Mutation Positive stage IB-IIIA non-small cell lung carcinoma,
    following complete tumour resection with or without adjuvant chemotherapy

    Detailed Description

    This is a phase 3 double-blind, randomized, placebo-controlled, study to assess the efficacy
    and safety of AZD9291 versus placebo in patients with stage IB-IIIA non-small cell lung
    cancer (NSCLC) with centrally confirmed, most common sensitising EGFR mutations (Ex19Del and
    L858R) either alone or in combination with other EGFR mutations as confirmed by a central
    test, who have had complete tumour resection, with or without postoperative adjuvant
    chemotherapy. Adjuvant chemotherapy should have consisted of a platinum based doublet given
    for a maximum of 4 cycles.

    Trial Arms

    Name Type Description Interventions
    AZD9291 Experimental AZD9291 (80 mg or 40 mg orally, once daily), in accordance with the randomization schedule. AZD9291 80 mg/40 mg
    Placebo AZD9291 Experimental Placebo AZD9291 (80 mg or 40 mg orally, once daily), in accordance with the randomization schedule. Placebo AZD9291 80 mg/40 mg

    Eligibility Criteria

    Inclusion Criteria:

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

    2. Histologically confirmed diagnosis of primary non small lung cancer (NSCLC) on
    predominantly non-squamous histology

    3. MRI or CT scan of the brain must be done prior to surgery as it is considered
    standard of care.

    4. Patients must be classified post-operatively as Stage IB, II or IIIA on the basis of
    pathologic criteria.

    5. Confirmation by the central laboratory that the tumour harbours one of the 2 common
    EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R),
    either alone or in combination with other EGFR mutations including T790M.

    6. Complete surgical resection of the primary NSCLC is mandatory. All gross disease must
    have been removed at the end of surgery. All surgical margins of resection must be
    negative for tumour.

    7. Complete recovery from surgery and standard post-operative therapy (if applicable) at
    the time of randomization.

    8. World Health Organization Performance Status of 0 to 1.

    9. Female patients should be using adequate contraceptive measures, should not be breast
    feeding, and must have a negative pregnancy test prior to first dose of study drug;
    or female patients must have an evidence of non-child-bearing potential.

    Exclusion Criteria:

    1. Treatment with any of the following:

    - Pre-operative or post-operative or planned radiation therapy for the current
    lung cancer

    - Pre-operative (neo-adjuvant) platinum based or other chemotherapy

    - Any prior anticancer therapy

    - Prior treatment with neoadjuvant or adjuvant EGFR-TKI at any time

    - Major surgery (including primary tumour surgery, excluding placement of vascular
    access) 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

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

    2. Patients who have had only segmentectomies or wedge resections

    3. History of other malignancies, except: adequately treated non-melanoma skin cancer,
    curatively treated in-situ cancer, or other solid tumours curatively treated with no
    evidence of disease for > 5 years following the end of treatment.

    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 QTc 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.

    8. Inadequate bone marrow reserve or organ function.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Disease free survival (DFS)

    Secondary Outcome Measures

    Disease free survival (DFS) rate at 2, 3 and 5 years

    Overall Survival (OS)

    Overall Survival rate at 5 years

    Patient health-related quality of life and symptoms (HRQoL) by SF-36v2 Health Survey

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

    Trial Keywords

    Stage IB-IIA-IIIA Non-Small Cell Lung Cancer; EGFRm+; Ex19Del; L858R; AZD9291; Phase III, adjuvant chemotherapy; complete tumour resection; EGFR-TKI