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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)

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ClinicalTrials.gov Identifier: NCT02511106
Recruitment Status : Recruiting
First Posted : July 29, 2015
Last Update Posted : November 28, 2018
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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 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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 700 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
Estimated Primary Completion Date : January 31, 2022
Estimated Study Completion Date : January 31, 2022

Resource links provided by the National Library of Medicine

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

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.

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.




Primary Outcome Measures :
  1. 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). Estimated median time to event of 46 and 66 months for those on placebo and AZD9291, respectively. ]
    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). Estimated median time to event of 46 and 66 months for those on placebo and AZD9291, respectively. ]
    Defined as the proportion 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 (estimated median 96 months for those on placebo) ]
    Defined as the time from the date of randomization until date of death due to any cause

  3. Overall Survival rate at 5 years [ Time Frame: From date of randomization until date of death due to any cause (estimated median 96 months for those on placebo) ]
    Defined as the proportion of patients alive at 5 years, estimated from a Kaplan Meier plot of OS at the time of the primary analysis

  4. Patient health-related quality of life and symptoms (HRQoL) by SF-36v2 Health Survey [ Time Frame: From date of randomization until treatment completion or discontinuation (max. 36 months) ]
    Measured by SF-36 Questionnaire consisting in 36 items that is an instrument for assessing a person's general health status over the past 28 days. The scores for each of the 8 health domain scores and for each of the physical and mental component summary measures from the SF-36 v2 will be summarized in terms of mean changes from baseline at each post-baseline assessment.

  5. Plasma concentrations of AZD9291 [ Time Frame: From date of dosing to month 24 (approximately 24 months) ]
    The pharmacokinetics exposure parameters derived from plasma concentrations of AZD9291

  6. Plasma concentrations of AZ5104 and AZ7550 metabolites and ratio of metabolite to AZD9291 [ Time Frame: From date of dosing to month 24 (approximately 24 months) ]
    The pharmacokinetics exposure parameters derived from plasma concentrations of AZ5104 and AZ7550 metabolites


Other Outcome Measures:
  1. Incidence of Adverse Events (AEs) [ Time Frame: From date of randomization until 28 days after treatment completion (max. 37 months) ]
    AEs graded by CTCAE version 4.0



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Ages Eligible for Study:   18 Years and older   (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.

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


Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: AstraZeneca Cancer Study Locator Service http://www.emergingmed.com/networks/AstraZeneca 1-877-400-4656 astrazeneca@emergingmed.com

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Sponsors and Collaborators
AstraZeneca

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02511106     History of Changes
Other Study ID Numbers: D5164C00001
2015-000662-65 ( EudraCT Number )
First Posted: July 29, 2015    Key Record Dates
Last Update Posted: November 28, 2018
Last Verified: November 2018

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:
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