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A Global Study to Assess the Effects of Osimertinib in Participants With EGFRm Stage IA2-IA3 NSCLC Following Complete Tumour Resection (ADAURA2)

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ClinicalTrials.gov Identifier: NCT05120349
Recruitment Status : Recruiting
First Posted : November 15, 2021
Last Update Posted : June 2, 2022
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
This is a global study to assess the effects of osimertinib in participants with EGFRm stage IA2-IA3 non-small cell lung cancer following complete tumour resection.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: Osimertinib Drug: Placebo Phase 3

Detailed Description:

This is a Phase III, double-blind, randomised, placebo-controlled, 2-arm, international study assessing the efficacy and safety of adjuvant osimertinib versus placebo in participants with stage IA2-IA3 EGFRm Non-Small Cell Lung Cancer, who have previously undergone complete tumour resection. All participants must have had a tumour which harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R).

Eligible participants will be randomised in a 1:1 ratio to one of the 2 intervention arms: osimertinib 80 mg or matching placebo, once daily for 3 years unless discontinuation criteria is met.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 380 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III, Double-blind, Randomised, Placebo-Controlled, International Study to Assess the Efficacy and Safety of Adjuvant Osimertinib Versus Placebo in Participants With EGFR Mutation-positive Stage IA2-IA3 Non-small Cell Lung Cancer, Following Complete Tumour Resection
Actual Study Start Date : February 21, 2022
Estimated Primary Completion Date : August 2, 2027
Estimated Study Completion Date : November 2, 2032

Resource links provided by the National Library of Medicine

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

Arm Intervention/treatment
Experimental: Osimertinib
Osimertinib 80mg, orally, once daily (Dose may be reduced to 40 mg once daily if required at the discretion of the investigator)
Drug: Osimertinib
The initial dose of Osimertinib 80mg once daily can be reduced to 40mg once daily. Treatment can continue until disease recurrence, unacceptable toxicity or other discontinuation criteria are met.
Other Name: AZD9291; TAGRISSO

Placebo Comparator: Placebo
Matching placebo for osimertinib, orally, once daily
Drug: Placebo
Matching placebo. Initial dose of 80mg once daily can be reduced to 40mg once daily.




Primary Outcome Measures :
  1. Disease-Free Survival (DFS) in high-risk stratum [ Time Frame: From date of randomisation up to approximately 10 years ]

    DFS is defined as the time from the date of randomisation until the date of disease recurrence or date of death (by any cause in the absence of recurrence), whichever occurs first.

    Stratification to the high risk stratum will be based on pathologic features assessed by central pathology review during screening.



Secondary Outcome Measures :
  1. Disease-Free Survival (DFS) in overall population [ Time Frame: From date of randomisation up to approximately 10 years ]
    DFS is defined as the time from the date of randomisation until the date of disease recurrence or date of death (by any cause in the absence of recurrence), whichever occurs first.

  2. Overall Survival (OS) in high-risk stratum and the overall population [ Time Frame: From date of randomization up to approximately 10 years ]
    OS is defined as the time from the date of randomisation until death due to any cause.

  3. PK plasma concentrations of osimertinib and of metabolite AZ5104 in overall population [ Time Frame: From date of randomisation up to approximately 10 years ]
    Ratio of metabolite-to-osimertinib to be calculated at predose, and at 0.5-2 hours postdose.

  4. Impact of osimertinib versus placebo on physical functioning [ Time Frame: From date of randomisation up to approximately 10 years ]
    Assess the impact of osimertinib versus placebo on physical functioning in both the high-risk stratum and the overall population as measured by SF-36 V2 health survey

  5. Central Nervous System (CNS) Disease-Free Survival (DFS) in both the high-risk stratum and the overall population [ Time Frame: From date of randomisation up to approximately 10 years ]
    CNS DFS is defined as the time from randomisation to the time of a CNS lesion (as assessed by investigator) or death due to any cause, regardless of whether the participant withdraws from study intervention or receives other anti-cancer therapy.

  6. Safety and tolerability in overall population [ Time Frame: From date of randomisation up to approximately 10 years ]
    AEs graded by CTCAE version 5.0



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 and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Male or female, at least ≥ 18 years.
  2. NSCLC, of non-squamous histology.
  3. Stage IA2 or IA3 disease, based on TNM8 classification.
  4. Complete surgical resection (R0) of the primary NSCLC by lobectomy, segmentectomy or sleeve resection.
  5. Complete recovery from surgery at the time of randomisation. Study intervention cannot commence within 4 weeks following surgery. No more than 12 weeks may have elapsed between surgery and randomisation for participants.
  6. World Health Organization performance status of 0 or 1.
  7. Provision of tumour sample for central pathology assessment of pathologic risk factors and to assess EGFR mutation status prior to randomisation.
  8. A tumour which harbours one of the 2 EGFR mutations (Ex19del, L858R) by cobas® EGFR Mutation Test v2 (Roche Diagnostics) or FoundationOne® test.
  9. Minimum life expectancy of > 6 months.
  10. Females must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of child-bearing potential, or must have evidence of non-child-bearing potential. Male subjects must be willing to use barrier contraception.

Exclusion Criteria

  1. Mixed small cell and non-small cell cancer history.
  2. Participants with incomplete (R1/R2) resection, or who have undergone pneumonectomy, bilobectomy or only wedge resection.
  3. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C and HIV.
  4. History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 5 years before the first dose of study intervention and of low potential risk for recurrence.
  5. Any of the following cardiac criteria:

    • Mean resting QTc interval > 470 ms, obtained from triplicate ECGs performed at screening.
    • Any abnormalities in rhythm, conduction, or morphology of resting ECG,
    • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events.
  6. History of interstitial lung disease.
  7. Inadequate bone marrow reserve or organ function.
  8. Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study intervention.
  9. Prior treatment with any anticancer therapy for NSCLC (including chemotherapy, radiotherapy, immunotherapy, and EGFR-TKIs).
  10. Major surgery or significant traumatic injury within 4 weeks of the first dose of study intervention.
  11. Participants currently receiving medications or herbal supplements known to be strong inducers of CYP3A4.

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): NCT05120349


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
Show Show 168 study locations
Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Jonathan Goldman, MD UCLA Department of Medicine
Principal Investigator: Yasuhiro Tsutani, MD, PhD Kindai University Facility of Medicine
Principal Investigator: Jie He, MD, PhD The Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS)
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT05120349    
Other Study ID Numbers: D516FC00001
First Posted: November 15, 2021    Key Record Dates
Last Update Posted: June 2, 2022
Last Verified: May 2022
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.

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 refer to our disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved, AstraZeneca will provide access to the de-identified 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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Osimertinib
Tagrisso
NSCLC
Non-small Cell Lung Cancer
Resectable
EGFRm Positive
Adjuvant
Stage IA2-IA3
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Osimertinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action