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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02511106
Recruitment Status : Active, not recruiting
First Posted : July 29, 2015
Results First Posted : July 27, 2021
Last Update Posted : April 19, 2023
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Description
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Brief Summary:
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

Condition or disease Intervention/treatment Phase
Stage IB-IIIA Non-small Cell Lung Carcinoma Drug: AZD9291 80 mg/40 mg Drug: Placebo AZD9291 80 mg/40 mg Drug: Open-label AZD9291 80 mg/40 mg Phase 3

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 682 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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).
Actual Study Start Date : October 21, 2015
Actual Primary Completion Date : January 17, 2020
Estimated Study Completion Date : June 30, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Osimertinib

Arms and Interventions
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Arm Intervention/treatment
Experimental: AZD9291
AZD9291 (80 mg or 40 mg orally, once daily), in accordance with the randomization schedule.
 Drug: AZD9291 80 mg/40 mg
The initial dose of AZD9291 80 mg once daily can be reduced to 40 mg once daily.

Drug: Open-label AZD9291 80 mg/40 mg
Eligible patients will be offered open-label osimertinib upon recurrence and in the absence of intervening systemic anti-cancer therapy.
Placebo Comparator: Placebo AZD9291
Matching placebo for AZD9291 (80 mg or 40 mg orally, once daily), in accordance with the randomization schedule.
 Drug: Placebo AZD9291 80 mg/40 mg
The initial dose of Placebo AZD9291 80 mg once daily can be reduced to 40 mg once daily.


Outcome Measures
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Primary Outcome Measures :
  1. Assess the Efficacy of AZD9291 Compared to Placebo as Measured by Disease Free Survival (DFS). [ Time Frame: From date of randomization until date of disease recurrence or death (by any cause in the absence of recurrence), up to approximately 4 years. ]
    Defined as the time from the date of randomization until the date of disease recurrence or death (by any cause in the absence of recurrence)


Secondary Outcome Measures :
  1. Disease Free Survival (DFS) Rate at 2, 3 and 5 Years [ Time Frame: From date of randomization until date of disease recurrence or death (by any cause in the absence of recurrence), up to approximately 4 years. Assessed at 2 years and 3 years. ]
    Defined as the percentage of patients alive and disease free at 2, 3 and 5 years, respectively, estimated from Kaplan Meier plots of the primary endpoint of DFS at the time of the primary analysis

  2. Overall Survival (OS) [ Time Frame: From date of randomization until date of death due to any cause, up to approximately 4 years. ]
    Defined as the time from the date of randomization until date of death due to any cause.

  3. Overall Survival (OS) [ Time Frame: From date of randomization until date of death due to any cause, up to approximately 4 years. ]
    Defined as the time from the date of randomization until date of death due to any cause

  4. Overall Survival Rate at 2, 3 and 5 Years [ Time Frame: From date of randomization until date of death due to any cause, up to approximately 4 years. Assessed at 2 years and 3 years. ]
    Defined as the percentage of patients alive at 2, 3 and 5 years, respectively, estimated from a Kaplan Meier plot of OS at the time of the primary analysis

  5. Patient Health-related Quality of Life and Symptoms (HRQoL) by SF-36v2 Health Survey. [ Time Frame: Measured by SF-36 Questionnaire at baseline, 12 week, 24 week and then every 24 weeks until study complete, disease recurrence or other discontinuation criteria met, up to approximately 3 years. ]
    Change from baseline will be calculated for each domain and summary scale at each scheduled post-baseline assessment. The SF-36 includes eight domains: Physical Functioning (PF); Role Limitations-Physical (RP), Vitality (VT), General Health Perceptions (GH), Bodily Pain (BP), Social Function (SF), Role Limitations-Emotional (RE), and Mental Health (MH) and two summary scores: The Physical Component Summary (PCS) and Mental Component Summary (MCS). Final scores for each scale range from 0-100 with higher scores indicating better health.

  6. Plasma Concentrations of AZD9291 [ Time Frame: Collected at pre-dose, 0.5-1.5hours and 2-4hours post-dose up to 96 weeks (approximately 24 months) ]
    The pharmacokinetics exposure parameters derived from plasma concentrations of AZD9291

  7. Plasma Concentrations of AZ5104 Metabolites [ Time Frame: From date of dosing to week 96 (approximately 24 months) ]
    The pharmacokinetics exposure parameters derived from plasma concentrations of AZ5104 metabolites

  8. Plasma Concentrations of AZ7550 Metabolites [ Time Frame: From date of dosing to week 96 (approximately 24 months) ]
    The pharmacokinetics exposure parameters derived from plasma concentrations of AZ7550 metabolites


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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 unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy.
  5. 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).
  6. 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.

  7. 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.
  8. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
  9. Inadequate bone marrow reserve or organ function.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02511106


Locations
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Sponsors and Collaborators
AstraZeneca
  Study Documents (Full-Text)

Documents provided by AstraZeneca:
Study Protocol  [PDF] January 8, 2021
Statistical Analysis Plan  [PDF] June 23, 2020

More Information
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Additional Information:
Cancer  This link exits the ClinicalTrials.gov site

Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02511106    
Other Study ID Numbers: D5164C00001
2015-000662-65 ( EudraCT Number )
First Posted: July 29, 2015    Key Record Dates
Results First Posted: July 27, 2021
Last Update Posted: April 19, 2023
Last Verified: April 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Keywords provided by AstraZeneca:
Stage IB-IIA-IIIA Non-Small Cell Lung Cancer; EGFRm+; Ex19Del; L858R; AZD9291; Phase III, adjuvant chemotherapy; complete tumour resection; EGFR-TKI
Additional relevant MeSH terms:
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Carcinoma
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
 Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Osimertinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action