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A Study of Osimertinib With or Without Chemotherapy Versus Chemotherapy Alone as Neoadjuvant Therapy for Patients With EGFRm Positive Resectable Non-Small Cell Lung Cancer (NeoADAURA)

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ClinicalTrials.gov Identifier: NCT04351555
Recruitment Status : Recruiting
First Posted : April 17, 2020
Last Update Posted : May 17, 2021
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE April 1, 2020
First Posted Date  ICMJE April 17, 2020
Last Update Posted Date May 17, 2021
Actual Study Start Date  ICMJE December 24, 2020
Estimated Primary Completion Date March 26, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 15, 2020)
Major Pathological Response (MPR) [ Time Frame: From date of randomization to an average of 12 weeks after the first dose ]
Defined as ≤10% residual cancer cells in the main tumour, as assessed per central pathology laboratory post-surgery
Original Primary Outcome Measures  ICMJE
 (submitted: April 15, 2020)
Major Pathological Response (MPR) [ Time Frame: From date of randomization to an average of 12 weeks after the first dose ]
Defined as ≤10% residual cancer cells in the surgical specimen, as assessed per central pathology laboratory post-surgery
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 15, 2020)
  • Pathological complete response (pCR) [ Time Frame: From date of randomization to an average of 12 weeks after the first dose ]
    Defined as absence of any residual cancer cells in the dissected tumour samples, including the main tumour and lymph nodes, assessed post-surgery
  • Event-free survival (EFS) [ Time Frame: Up to approximately 42 months after the last patient is randomized ]
    An event is defined as documented disease progression that precludes surgery or requires non-protocol therapy; recurrence or a new lesion, local or distant (a new primary malignancy confirmed by pathology is not considered to be an EFS event.); death due to any cause
  • Overall Survival (OS) [ Time Frame: Up to approximately 5.5 years after the last patient is randomized ]
    Patients will be followed up to approximately 5.5 years after they are randomized.
  • Disease free survival (DFS) [ Time Frame: From date of randomization up to approximately 42 months after date of resection ]
    DFS is defined as the time from the date of surgery until the first date of disease recurrence (local or distant) or date of death due to any cause, whichever occurs first.
  • Downstaging [ Time Frame: From date of randomization to an average of 12 weeks after the first dose ]
    Measured using pathologic mediastinal lymph node evaluation
  • Difference between treatment arms in change from baseline in EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 items) [ Time Frame: From randomization to 264 weeks post-surgery ]
    Assess disease-related symptoms, functioning, and global health status/quality-of-life in patients
  • Concordance of EGFRm status between tumour tissue DNA and patient-matched plasma-derived ctDNA [ Time Frame: Baseline ]
  • Corcordance of EGFR mutation status between the local and central cobas EGFR mutation test results from baseline tumour samples [ Time Frame: Baseline ]
  • PK plasma concentrations of osimertinib [ Time Frame: From the pre-dose of Cycle 2 to post-dose of Cycle 3 (each cycle is 21 days) ]
  • Difference between treatment arms in change from baseline in EORTC QLQ-LC13 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 items) [ Time Frame: From randomization to 264 weeks post-surgery ]
    Assess lung cancer-associated symptoms and side effects from conventional chemotherapy and radiotherapy
Original Secondary Outcome Measures  ICMJE
 (submitted: April 15, 2020)
  • Pathological complete response (pCR) [ Time Frame: From date of randomization to an average of 12 weeks after the first dose ]
    Defined as absence of any residual cancer cells in the surgical specimen assessed post-surgery
  • Event-free survival (EFS) [ Time Frame: Up to approximately 21 months after the last patient is randomized ]
    An event is defined as documented disease progression that precludes surgery or requires non-protocol therapy; recurrence or a new lesion, local or distant (a new primary malignancy confirmed by pathology is not considered to be an EFS event.); death due to any cause
  • Overall Survival (OS) [ Time Frame: Up to approximately 5.5 years after the last patient is randomized ]
    Patients will be followed up to approximately 5.5 years after they are randomized.
  • Disease free survival (DFS) [ Time Frame: From date of randomization up to approximately 15 months after date of resection ]
    DFS is defined as the time from the date of surgery until the first date of disease recurrence (local or distant) or date of death due to any cause, whichever occurs first. If there is residual disease after surgery (eg. positive margins), the DFS event is the date of surgery.
  • Downstaging [ Time Frame: From date of randomization to an average of 12 weeks after the first dose ]
    Measured using lymph node staging
  • Difference between treatment arms in change from baseline in EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 items) [ Time Frame: From randomization to 24 weeks post-surgery ]
    Assess disease-related symptoms, functioning, and global health status/quality-of-life in patients
  • Concordance of EGFRm status between tumour tissue DNA and patient-matched plasma-derived ctDNA [ Time Frame: Baseline ]
  • Corcordance of EGFR mutation status between the local and central cobas EGFR mutation test results from baseline tumour samples [ Time Frame: Baseline ]
  • PK plasma concentrations of osimertinib [ Time Frame: From the pre-dose of Cycle 2 to post-dose of Cycle 3 (each cycle is 21 days) ]
  • Difference between treatment arms in change from baseline in EORTC QLQ-LC13 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 items) [ Time Frame: From randomization to 24 weeks post-surgery ]
    Assess lung cancer-associated symptoms and side effects from conventional chemotherapy and radiotherapy
Current Other Pre-specified Outcome Measures
 (submitted: September 15, 2020)
  • Cure rate [ Time Frame: From the surgery until 5 years after surgery ]
    The cure rate is defined as the percentage of people in this study who are still alive and disease free for a certain period of time after they finished the surgery. Here 5-year landmark cure rate will be calculated in the same time as OS analysis.
  • Number of adverse events as assessed by CTCAE 5.0 and other clinical variables for safety and tolerability profile of neoadjuvant osimertinib as monotherapy or in combination with chemotherapy prior to surgery compared with chemotherapy alone [ Time Frame: From the time of enrollment to either 28-days after the last dose of last study treatment for patients who do not undergo surgery, or 90-days post-surgery ]
    Other clinical variables include deaths, laboratory data, vital signs (pulse and BP), ECG, LVEF, ECOG performance status, and ophthalmologic assessment
  • MPR using plasma-derived circulating-free tumour DNA (ctDNA) [ Time Frame: From randomization to 5 years post-surgery ]
Original Other Pre-specified Outcome Measures
 (submitted: April 15, 2020)
  • Cure rate [ Time Frame: From the surgery until five years after surgery ]
    The cure rate is defined as the percentage of people in this study who are still alive and disease free for a certain period of time after they finished the surgery. Here five-year landmark cure rate will be calculated in the same time as OS analysis.
  • Number of adverse events as assessed by CTCAE 5.0 and other clinical variables for safety and tolerability profile of neoadjuvant osimertinib as monotherapy or in combination with chemotherapy prior to surgery compared with chemotherapy alone [ Time Frame: From the time of enrollment to either 28-days after the last dose of last study treatment for patients who do not undergo surgery, or 90-days post-surgery ]
    Other clinical variables include deaths, laboratory data, vital signs (pulse and BP), ECG, LVEF, ECOG performance status, and ophthalmologic assessment
  • MPR using plasma-derived circulating-free tumour DNA (ctDNA) [ Time Frame: From randomization to week 264 post-surgery ]
 
Descriptive Information
Brief Title  ICMJE A Study of Osimertinib With or Without Chemotherapy Versus Chemotherapy Alone as Neoadjuvant Therapy for Patients With EGFRm Positive Resectable Non-Small Cell Lung Cancer
Official Title  ICMJE A Phase III, Randomised, Controlled, Multi-center, 3-Arm Study of Neoadjuvant Osimertinib as Monotherapy or in Combination With Chemotherapy Versus Standard of Care Chemotherapy Alone for the Treatment of Patients With Epidermal Growth Factor Receptor Mutation Positive, Resectable Non-small Cell Lung Cancer
Brief Summary This is a Phase III, randomised, controlled, 3-arm, multi-centre study of neoadjuvant osimertinib as monotherapy or in combination with chemotherapy, versus SoC chemotherapy alone, for the treatment of patients with resectable EGFRm Non-Small Cell Lung Cancer
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:

The two arms with SoC chemotherapy (placebo plus chemotherapy versus osimertinib plus chemotherapy) will be double-blinded and placebo-controlled.

Osimertinib monotherapy arm will be open label, sponsor-blind.

Primary Purpose: Treatment
Condition  ICMJE Non-Small Cell Lung Cancer
Intervention  ICMJE
  • Drug: Osimertinib
    Oral
    Other Name: AZD9291; TAGRISSO
  • Drug: Cisplatin
    Cisplatin (75mg/m2) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles.
  • Drug: Carboplatin
    Carboplatin (AUC5) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles
  • Drug: Placebo
    Oral
  • Drug: Pemetrexed
    Pemetrexed (500 mg/m2) to be administered with cisplatin or carboplatin on Day 1 of every 3-week cycle for 3 cycles
Study Arms  ICMJE
  • Placebo Comparator: Arm 1: Placebo with platinum-based chemotherapy
    Placebo plus investigator's choice of platinum-based standard of care chemotherapy (pemetrexed/carboplatin or pemetrexed/cisplatin)
    Interventions:
    • Drug: Cisplatin
    • Drug: Carboplatin
    • Drug: Placebo
    • Drug: Pemetrexed
  • Experimental: Arm 2: Osimertinib with platinum-based chemotherapy
    Osimertinib 80 mg QD (Dose may be reduced to 40 mg QD at the discretion of the investigator) plus investigator's choice of platinum-based standard of care chemotherapy (pemetrexed/carboplatin or pemetrexed/cisplatin)
    Interventions:
    • Drug: Osimertinib
    • Drug: Cisplatin
    • Drug: Carboplatin
    • Drug: Pemetrexed
  • Experimental: Arm 3: Osimertinib monotherapy
    Osimertinib 80 mg QD (Dose may be reduced to 40 mg QD at the discretion of the investigator)
    Intervention: Drug: Osimertinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 15, 2020)
328
Original Estimated Enrollment  ICMJE
 (submitted: April 15, 2020)
351
Estimated Study Completion Date  ICMJE March 29, 2029
Estimated Primary Completion Date March 26, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female, at least 18 years of age. For patients aged <20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative
  • Histologically or cytologically documented non-squamous NSCLC with completely resectable (Stage II - IIIB N2) disease (according to Version 8 of the IASLC Cancer Staging Manual [IASLC Staging Manual in Thoracic Oncology 2016]).
  • Complete surgical resection of the primary NSCLC must be deemed achievable, as assessed by a MDT evaluation (which should include a thoracic surgeon, specialised in oncologic procedures).
  • Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1 at enrolment, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing
  • A tumour which 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 (ie, T790M, G719X, Exon20 insertions, S7681 and L861Q).

Exclusion Criteria:

  • Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
  • History of another primary malignancy, except for the following: Malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of investigational product (IP) and of low potential risk for recurrence; Adequately treated non-melanoma skin cancer or lentigo malignancy without evidence of disease; Adequately treated carcinoma in situ without evidence of disease
  • Patients who have pre-operative radiotherapy treatment as part of their care plan
  • Mixed small cell and NSCLC histology
  • Stages I, IIIB N3, IIIC, IVA, and IVB NSCLC
  • T4 tumours infiltrating the aorta, the oesophagus and/or the heart; and/or any bulky N2 disease
  • Patients who are candidates to undergo only segmentectomies or wedge resections
  • Prior treatment with any systemic anti-cancer therapy for NSCLC including chemotherapy, biologic therapy, immunotherapy, or any investigational drug
  • Prior treatment with EGFR-TKI therapy
  • Current use of (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of cytochrome P450 (CYP) 3A4 (at least 3 weeks prior)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: AstraZeneca Cancer Study Locator 1-877-400-4656 astrazeneca@emergingmed.com
Listed Location Countries  ICMJE Austria,   Brazil,   Bulgaria,   Chile,   China,   Germany,   India,   Israel,   Italy,   Japan,   Korea, Republic of,   Peru,   Poland,   Russian Federation,   Spain,   Switzerland,   Taiwan,   Thailand,   Turkey,   United Kingdom,   United States,   Vietnam
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04351555
Other Study ID Numbers  ICMJE D516AC00001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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.
Supporting Materials: Study Protocol
Supporting Materials: 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 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
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jamie Chaft, MD Memorial Sloan Kettering, USA
Principal Investigator: Masahiro Tsuboi, MD National Cancer Center Hospital East, Japan
Principal Investigator: Walter Weder, MD Thoraxchirurgie Bethanien, Switzerland
PRS Account AstraZeneca
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP