Clincosm LogoSign in Get a demo

NeoADAURA: 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

Sponsor
AstraZeneca (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04351555
Collaborator
(none)
328
Enrollment
216
Locations
3
Arms
99.4
Anticipated Duration (Months)
1.5
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
328 participants
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
Official Title:
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
Actual Study Start Date :
Dec 16, 2020
Anticipated Primary Completion Date :
Mar 26, 2024
Anticipated Study Completion Date :
Mar 29, 2029

Arms and Interventions

Arm Intervention/Treatment
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)

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
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)

Drug: Osimertinib
Oral
Other Names:
  • 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: Pemetrexed
    Pemetrexed (500 mg/m2) to be administered with cisplatin or carboplatin on Day 1 of every 3-week cycle for 3 cycles
    Experimental: Arm 3: Osimertinib monotherapy

    Osimertinib 80 mg QD (Dose may be reduced to 40 mg QD at the discretion of the investigator)

    Drug: Osimertinib
    Oral
    Other Names:
  • AZD9291; TAGRISSO

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Major Pathological Response (MPR) [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

    Secondary Outcome Measures

    1. Pathological complete response (pCR) [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

    2. Event-free survival (EFS) [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

    3. Overall Survival (OS) [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.

    4. Disease free survival (DFS) [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.

    5. Downstaging [From date of randomization to an average of 12 weeks after the first dose]

      Measured using pathologic mediastinal lymph node evaluation

    6. 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) [From randomization to 264 weeks post-surgery]

      Assess disease-related symptoms, functioning, and global health status/quality-of-life in patients

    7. Concordance of EGFRm status between tumour tissue DNA and patient-matched plasma-derived ctDNA [Baseline]

    8. Corcordance of EGFR mutation status between the local and central cobas EGFR mutation test results from baseline tumour samples [Baseline]

    9. PK plasma concentrations of osimertinib [From the pre-dose of Cycle 2 to post-dose of Cycle 3 (each cycle is 21 days)]

    10. 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) [From randomization to 264 weeks post-surgery]

      Assess lung cancer-associated symptoms and side effects from conventional chemotherapy and radiotherapy

    Other Outcome Measures

    1. Cure rate [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.

    2. 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 [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

    3. MPR using plasma-derived circulating-free tumour DNA (ctDNA) [From randomization to 5 years post-surgery]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 100 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Birmingham Alabama United States 35233
    2 Research Site Duarte California United States 91010
    3 Research Site Los Angeles California United States 90048
    4 Research Site San Francisco California United States 94143
    5 Research Site Santa Monica California United States 90404
    6 Research Site Santa Rosa California United States 95403
    7 Research Site New Haven Connecticut United States 06510
    8 Research Site Washington District of Columbia United States 20007
    9 Research Site Miami Florida United States 33136
    10 Research Site Chicago Illinois United States 60637
    11 Research Site Boston Massachusetts United States 02215
    12 Research Site Ann Arbor Michigan United States 48109
    13 Research Site Lebanon New Hampshire United States 03756
    14 Research Site Commack New York United States 11725
    15 Research Site New York New York United States 10032
    16 Research Site Houston Texas United States 77030
    17 Research Site San Antonio Texas United States 78229
    18 Research Site Fairfax Virginia United States 22031
    19 Research Site Seattle Washington United States 98104
    20 Research Site Linz Austria 4020
    21 Research Site Vienna Austria
    22 Research Site Wien Austria 1210
    23 Research Site Barretos Brazil 14784-400
    24 Research Site Belo Horizonte Brazil 30110-022
    25 Research Site Bento Goncalves Brazil 95700-084
    26 Research Site Fortaleza Brazil 60135-040
    27 Research Site Ibirapuera Brazil 04501-000
    28 Research Site Jau Brazil 17204310
    29 Research Site Porto Alegre Brazil 90035-000
    30 Research Site Porto Alegre Brazil 90610-000
    31 Research Site Recife Brazil 52010-075
    32 Research Site Ribeirão Preto Brazil 14021-636
    33 Research Site Rio de Janeiro Brazil 22271-110
    34 Research Site Santa Maria Brazil 97015-450
    35 Research Site Sao Paulo Brazil 01321-001
    36 Research Site Sao Paulo Brazil 01327-001
    37 Research Site São José do Rio Preto Brazil 15090-000
    38 Research Site São Paulo Brazil 04038-034
    39 Research Site Panagyurishte Bulgaria 4500
    40 Research Site Pleven Bulgaria 5804
    41 Research Site Plovdiv Bulgaria 4004
    42 Research Site Sofia Bulgaria 1113
    43 Research Site Sofia Bulgaria 1407
    44 Research Site Sofia Bulgaria 1527
    45 Research Site Sofia Bulgaria 1618
    46 Research Site Toronto Ontario Canada M5G 2N2
    47 Research Site Montreal Quebec Canada H2X 0A9
    48 Research Site Montreal Quebec Canada H4A 3J1
    49 Research Site La Serena Chile 1720430
    50 Research Site Las Condes Chile 7560908
    51 Research Site Providencia Chile 7510032
    52 Research Site Santiago Chile 7500713
    53 Research Site Santiago Chile 7500921
    54 Research Site Santiago Chile 7520349
    55 Research Site Santiago Chile 8380455
    56 Research Site Santiago Chile 8420383
    57 Research Site Viña del Mar Chile 2540488
    58 Research Site Beijing China 100029
    59 Research Site Beijing China 100029
    60 Research Site Beijing China 100142
    61 Research Site Beijing China 100191
    62 Research Site Beijing China CN-100730
    63 Research Site Changsha China 410008
    64 Research Site Changsha China 410013
    65 Research Site Chengdu China 610041
    66 Research Site Chongqing China 400037
    67 Research Site Guangzhou China 510062
    68 Research Site Guangzhou China 510095
    69 Research Site Guangzhou China 510120
    70 Research Site Guangzhou China 510515
    71 Research Site Hangzhou China 310006
    72 Research Site Hangzhou China 310009
    73 Research Site Hangzhou China 310022
    74 Research Site Hefei China 230001
    75 Research Site Kunming China 650118
    76 Research Site Linhai China 317000
    77 Research Site Nanchang China 330006
    78 Research Site Nanjing China 210029
    79 Research Site Nantong China 226001
    80 Research Site Shandong China
    81 Research Site Shanghai China 200030
    82 Research Site Shanghai China 200032
    83 Research Site Shanghai China 200433
    84 Research Site Shenzhen China 518053
    85 Research Site Suzhou China 215006
    86 Research Site Urumqi China 830000
    87 Research Site Wanzhou China 404000
    88 Research Site Wenzhou China CN-325000
    89 Research Site Xiamen China 361004
    90 Research Site Yangzhou China 225001
    91 Research Site Zhengzhou China 450008
    92 Research Site Angers France 49033
    93 Research Site Avignon Cedex France 84902
    94 Research Site Clermont Ferrand France 63011
    95 Research Site Toulon Cedex 9 France 83800
    96 Research Site Berlin Germany 12351
    97 Research Site Bielefeld Germany 33611
    98 Research Site Esslingen a.N. Germany 73730
    99 Research Site Freiburg Germany 79106
    100 Research Site Gauting Germany 82131
    101 Research Site Georgsmarienhuette Germany 49124
    102 Research Site Halle Germany 06120
    103 Research Site Hamburg Germany 21075
    104 Research Site Heidelberg Germany 69126
    105 Research Site Homburg Germany 66421
    106 Research Site Köln Germany 51109
    107 Research Site Oldenburg Germany 26121
    108 Research Site Würzburg Germany 97067
    109 Research Site Kolkata India 700160
    110 Research Site Manipal India 576104
    111 Research Site Mumbai India 400012
    112 Research Site Mumbai India 400036
    113 Research Site Namakkal India 637001
    114 Research Site New Delhi India 110029
    115 Research Site Rohini India 110 085
    116 Research Site Haifa Israel 3109601
    117 Research Site Jerusalem Israel 91120
    118 Research Site Kfar Saba Israel 95847
    119 Research Site Petah Tikva Israel 49100
    120 Research Site Ramat Gan Israel 5265601
    121 Research Site Bari Italy 70124
    122 Research Site Firenze Italy 50134
    123 Research Site Monza Italy 20900
    124 Research Site Orbassano Italy 10043
    125 Research Site Padova Italy 35128
    126 Research Site Roma Italy 00144
    127 Research Site Roma Italy 00168
    128 Research Site Rozzano Italy 20089
    129 Research Site Varese Italy 21100
    130 Research Site Akashi-shi Japan 673-8558
    131 Research Site Bunkyo-ku Japan 113-8431
    132 Research Site Chiba-shi Japan 260-8677
    133 Research Site Hiroshima-shi Japan 734-8551
    134 Research Site Kashiwa Japan 227-8577
    135 Research Site Koto-ku Japan 135-8550
    136 Research Site Kyoto-shi Japan 606-8507
    137 Research Site Niigata-shi Japan 951-8566
    138 Research Site Osaka-shi Japan 541-8567
    139 Research Site Osakasayama-shi Japan 589-8511
    140 Research Site Sakai-shi Japan 591-8555
    141 Research Site Sendai-shi Japan 980-0873
    142 Research Site Shinjuku-ku Japan 160-0023
    143 Research Site Sunto-gun Japan 411-8777
    144 Research Site Yokohama-shi Japan 241-8515
    145 Research Site Daegu Korea, Republic of 41404
    146 Research Site Daegu Korea, Republic of 41931
    147 Research Site Hwasun-gun Korea, Republic of 58128
    148 Research Site Incheon Korea, Republic of 21431
    149 Research Site Seoul Korea, Republic of 02447
    150 Research Site Seoul Korea, Republic of 05030
    151 Research Site Seoul Korea, Republic of 08308
    152 Research Site Yangsan-si Korea, Republic of 50612
    153 Research Site Aguascalientes Mexico 20230
    154 Research Site D.F Mexico 14050
    155 Research Site Mexico City Mexico '14080
    156 Research Site Mexico City Mexico 06720
    157 Research Site La Libertad Peru 13013
    158 Research Site Lima Peru 15036
    159 Research Site Lima Peru L41
    160 Research Site Lima Peru Lima 32
    161 Research Site Lima Peru LIMA 34
    162 Research Site Białystok Poland 15-540
    163 Research Site Kraków Poland 31-202
    164 Research Site Olsztyn Poland 10-357
    165 Research Site Otwock Poland 05-400
    166 Research Site Poznań Poland 60-569
    167 Research Site Szczecin Poland 71-455
    168 Research Site Warszawa Poland 02-781
    169 Research Site Warszawa Poland 04-141
    170 Research Site Wrocław Poland 53-439PL
    171 Research Site Kazan Russian Federation 420029
    172 Research Site Krasnoyarsk Russian Federation 660133
    173 Research Site Moscow Russian Federation 105229
    174 Research Site Moscow Russian Federation 121205
    175 Research Site Nizhniy Novgorod Russian Federation 603081
    176 Research Site Obninsk Russian Federation 249036
    177 Research Site Perm Russian Federation 614990
    178 Research Site Saint Petersburg Russian Federation 191036
    179 Research Site Saint Petersburg Russian Federation 197758
    180 Research Site Saint-Petersburg Russian Federation 197758
    181 Research Site St. Petersburg Russian Federation 197022
    182 Research Site Tomsk Russian Federation 634063
    183 Research Site Singapore Singapore 308433
    184 Research Site Barcelona Spain 08035
    185 Research Site Barcelona Spain 08036
    186 Research Site Madrid Spain 28040
    187 Research Site Majadahonda Spain 28222
    188 Research Site Málaga Spain 29010
    189 Research Site Bellinzona Switzerland 6500
    190 Research Site Zürich Switzerland CH-8091
    191 Research Site Taichung Taiwan 40201
    192 Research Site Taichung Taiwan 40447
    193 Research Site Tainan City Taiwan 73657
    194 Research Site Taipei City Taiwan 110
    195 Research Site Taipei Taiwan 10002
    196 Research Site Taipei Taiwan 112
    197 Research Site Taipei Taiwan 235
    198 Research Site Bangkok Thailand 10330
    199 Research Site Bangkok Thailand 10400
    200 Research Site Chiang Mai Thailand 50200
    201 Research Site Khon Kaen Thailand 40002
    202 Research Site Pathumthani Thailand 12120
    203 Research Site Pathumwan Thailand 10330
    204 Research Site Phisanulok Thailand 65000
    205 Research Site Ankara Turkey 06010
    206 Research Site Ankara Turkey 6500
    207 Research Site Istanbul Turkey 34010
    208 Research Site Istanbul Turkey 34214
    209 Research Site Izmir Turkey 35110
    210 Research Site Malatya Turkey 44280
    211 Research Site Birmingham United Kingdom B9 5SS
    212 Research Site Liverpool United Kingdom L7 8YA
    213 Research Site Manchester United Kingdom M23 9LT
    214 Research Site Hanoi Vietnam 100000
    215 Research Site Ho Chi Minh Vietnam 700000
    216 Research Site Ho Chi Minh Vietnam 70000

    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    • 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT04351555
    Other Study ID Numbers:
    • D516AC00001
    First Posted:
    Apr 17, 2020
    Last Update Posted:
    Jul 25, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by AstraZeneca
    Resectable; NSCLC; Osimertinib; EGFRm Positive; Neoadjuvant; Adjuvant
    Additional relevant MeSH terms:
    Lung Neoplasms
    Carcinoma, Non-Small-Cell Lung
    Carboplatin
    Pemetrexed
    Osimertinib

    Study Results

    No Results Posted as of Jul 25, 2022