A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter, International Study of Osimertinib as Maintenance Therapy in Patients With Locally Advanced, Unresectable EGFR Mutation-positive Non-Small Cell Lung Cancer (Stage III) Whose Disease Has Not Progressed Following Definitive Platinum-based Chemoradiation Therapy (LAURA).

ClinicalTrials.gov processed this data on April 25, 2024. Link to the current ClinicalTrials.gov record.

Recruitment Status

ACTIVE, NOT RECRUITING (See Contacts and Locations)
Verified April 2024 by AstraZeneca

Sponsor

AstraZeneca

Information Provided by (Responsible Party)

AstraZeneca

Clinicaltrials.gov Identifier

NCT03521154
Other Study ID Numbers: D5160C00048
First Submitted: April 20, 2018
First Posted: May 11, 2018
Last Update Posted: April 26, 2024
Last Verified: April 2024
History of Changes

Listing a study on this site does not mean it has been evaluated by the U.S. Federal Government. The safety and scientific validity of a study listed on ClinicalTrials.gov is the responsibility of the study sponsor and investigators. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating.

ClinicalTrials.gov, a resource provided by the U.S. National Library of Medicine (NLM), is a registry and results information database of clinical research studies sponsored or funded by a broad range of public and private organizations around the world. Not all studies listed on ClinicalTrials.gov are funded by the National Institutes of Health (NIH) or other agencies of the U.S. Federal Government. Not all listed studies are regulated and/or reviewed by the U.S. Food and Drug Administration or other governmental entities.

Information on ClinicalTrials.gov is provided by study sponsors and investigators, and they are responsible for ensuring that the studies follow all applicable laws and regulations. NLM staff do not verify the scientific validity or relevance of the submitted information beyond a limited quality control review for apparent errors, deficiencies, or inconsistencies.

Choosing to participate in a study is an important personal decision. Before you participate in a study, discuss all options with your health care provider and other trusted advisors. For more information about participating in clinical studies, see Learn About Clinical Studies, which includes questions that you might want to ask before deciding to participate in a study.

For more information about using the information on ClinicalTrials.gov, please also see Terms and Conditions.

See also the Web Policies and Notices for the NIH web site.

Study Description

This is a phase 3 double-blind, randomized, placebo-controlled, study to assess the efficacy and safety of osimertinib following chemoradiation in patients with stage III unresectable EGFR mutation-positive NSCLC, including the most common EGFR sensitising mutations (Ex19Del and L858R), either alone or in combination with other EGFR mutations. Chemoradiation may have been given either given concurrently or sequentially. Patients whose disease has not progressed following chemoradiation will be randomised within 6 weeks of completion of chemoradiation to receive osimertinib or placebo in a 2:1 ratio, and treatment will be continued until disease progression, unacceptable toxicity or other discontinuation criteria are met. After progression, patients can be unblinded and may receive open-label osimertinib. After the final OS analysis, the study blind will be broken and patients still receiving open-label osimertinib will be supplied with open-label osimertinib by AstraZeneca for as long as their treating physician considers they are deriving clinical benefit.
Condition or Disease Intervention/Treatment
  • Non Small Cell Lung Cancer (Stage III)
  • Drug: Osimertinib 80mg/40mg
  • Drug: Placebo Osimertinib 80mg/40mg

Study Design

Study TypeInterventional
Actual Enrollment216 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingDouble
Primary PurposeTreatment
Official TitleA Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter, International Study of Osimertinib as Maintenance Therapy in Patients With Locally Advanced, Unresectable EGFR Mutation-positive Non-Small Cell Lung Cancer (Stage III) Whose Disease Has Not Progressed Following Definitive Platinum-based Chemoradiation Therapy (LAURA).
Study Start DateJuly 19, 2018
Actual Primary Completion DateJanuary 5, 2024
Anticipated Study Completion DateJune 29, 2026

Groups and Cohorts

Group/ CohortIntervention/ Treatment
  • Osimertinib
    • Osimertinib (80mg or 40mg orally, once daily), in accordance with the randomization schedule.
  • Drug: Osimertinib 80mg/40mg
    • The initial dose of Osimertinib 80mg once daily can be reduced to 40mg once daily. Treatment can continue until disease progression, unacceptable toxicity or other discontinuation criteria are met.
  • Placebo Osimertinib
    • Matching placebo for Osimertinib (80mg or 40mg orally, once daily), in accordance with the randomization schedule
  • Drug: Placebo Osimertinib 80mg/40mg

    Outcome Measures

    Primary Outcome Measures

    1. Progression-free survival (PFS) [Approximately 13 months]
      Defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression, based on blinded independent central review assessment according to RECIST 1.1

    Secondary Outcome Measures

    1. PFS in patients with EGFR Ex19del or L858R mutation [Approximately 13 months]
      Defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression.' based on blinded independent central review assessment according to RECIST 1.1
    2. PFS in patients with EGFR mutations Ex19del or L858R detectable in plasma-derived ctDNA [Approximately 13 months]
      Defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression.' based on blinded independent central review assessment according to RECIST 1.1
    3. Time to CNS PFS [Approximately 13 months]
      Defined as earlier event of CNS progression or death based on blinded independent central review assessment according to RECIST 1.1
    4. Overall survival (OS) [Approximately 45 months]
      Defined as the time from randomization until death from any cause
    5. Objective response rate (ORR) [Approximately 13 months]
      Defined as the number (%) of patients with measurable disease with at least 1 visit response of CR (Complete response) or PR (Partial response) based on blinded independent central review assessment according to RECIST 1.1
    6. Duration of response (DoR) [Approximately 13 months]
      Defined as the time from the date of first documented response (i.e., subsequently confirmed) until the date of documented progression or death in the absence of disease progression based on blinded independent central review assessment according to RECIST 1.1
    7. Disease control rate (DCR) [Approximately 13 months]
      Defined as Disease control rate is defined as the percentage of subjects who have a best overall response of CR or PR or SD based on blinded independent central review assessment according to RECIST 1.1
    8. Tumor shrinkage [Approximately 13 months]
      Defined as the relative change in the sum of the longest diameters of RECIST target lesions at the nadir in the absence of new lesions or progression of non-target lesions compared to baseline based on blinded independent central review assessment according to RECIST 1.1
    9. Time to death or distant metastases (TTDM) [Approximately 13 months]
      Defined as the time from the date of randomization until the first date of distant metastasis or date of death in the absence of distant metastasis based on blinded independent central review assessment according to RECIST 1.1
    10. Time to treatment discontinuation [Approximately 13 months]
      Defined as the time from randomization to the earlier of the date of study treatment discontinuation (regardless of the reason for study treatment discontinuation) or death
    11. Second progression free survival on a subsequent treatment (PFS2) [Approximately 13 months]
      Time from randomisation to second progression (PFS2) is defined as the time from the date of randomisation to the earliest of the progression event subsequent to that used for the primary variable PFS or date of death after starting subsequent anti-cancer treatment.
    12. Time to first subsequent therapy (TFST) [Approximately 13 months]
      Defined as the time from the date of randomization to the earlier of the date of anti-cancer therapy start date following study drug discontinuation or death
    13. Time to second subsequent therapy (TSST) [Approximately 21 months]
      Defined as the time from the date of randomization to the earlier of the date of second subsequent anti-cancer therapy start date following study drug discontinuation or death.
    14. Patients reported disease-related symptoms and HRQoL by EORTC QLQ-LC13 and EORTC QLQ-30 questionnaires [Approximately 21 months]
      Change in symptoms from baseline
    15. Incidence of Adverse Events (AEs) [Approximately 13 months]
      AEs graded by CTCAE version 5.0
    16. Plasma concentrations of osimertinib and AZD5104 [Trough concentrations at Week 4,12 and 24]
      The pharmacokinetics exposure parameters derived from plasma concentrations of osimertinib and AZD5104

    Eligibility Criteria

    Ages Eligible for Study 18 Years to 130 Years (Adult, Older Adult)
    Sexes Eligible for Study All
    Accepts Healthy Volunteers No
    Inclusion Criteria
    • ale or female aged at least 18 years.
    • Patients with histologically documented NSCLC of predominantly non-squamous Pathology who present with locally advanced, unresectable (Stage III) disease (according to Version 8 of the International Association for the Study of Lung Cancer [IASLC] Staging Manual in Thoracic Oncology).
    • The tumor harbours one of the two common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations, assessed by cobas® EGFR Mutation Test v2 (Roche Diagnostics) or FoundationOne® test in a CLIA certified (USA sites) or an accredited local laboratory (sites outside of the USA) or by central testing (cobas® v2 only).
    • Patients must have received either concurrent chemoradiation or sequential chemoradiation including at least 2 cycles of platinum based chemotherapy and a total dose of radiation of 60 Gy ±10% (54 to 66 Gy).
    • Chemoradiation must be completed ≤6 weeks prior to randomization.
    • Patients must not have had disease progression during or following definitive platinum-based, chemoradiation therapy.
    • World Health Organization (WHO) performance status of 0 or 1.
    • Life expectancy >12 weeks at Day 1.
    • Female patients who are not abstinent (in line with the preferred and usual lifestyle choice) must be using adequate contraceptive measures, must 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-childbearing potential.
    Exclusion Criteria
    • ixed small cell and non-small cell lung cancer histology
    • History of interstitial lung disease (ILD) prior to chemoradiation
    • Symptomatic pneumonitis following chemoradiation
    • Any unresolved toxicity Common Terminology Criteria for Adverse Events (CTCAE) > Grade 2 from the prior chemoradiation therapy
    • Any of the following cardiac criteria:
    • Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs
    • Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG
    • Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes
    • Inadequate bone marrow reserve or organ function
    • History of other malignancies, except: adequately treated non-melanoma skin cancer or lentigo maligna , curatively treated in-situ cancer, or other solid tumors curatively treated with no evidence of disease for > 5 years following the end of treatment and which, in the opinion of the treating physician, do not have a substantial risk of recurrence of the prior malignancy.
    • 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).
    • Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of osimertinib
    • Prior treatment with any prior chemotherapy, radiation therapy, immunotherapy or investigational agents for NSCLC outside of that received in the definitive setting for Stage III disease (chemotherapy and radiotherapy in SCRT and CCRT regimens is allowed for treatment of Stage III disease).
    • Prior treatment with EGFR-TKI therapy
    • Major surgery as defined by the investigator within 4 weeks of the first dose of study drug.
    • Patients currently receiving (unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4 (at least 3 weeks prior to receiving the first dose of study drug).
    • Contraindication to MRI, including but not limited to, claustrophobia, pace makers, metal implants, intracranial surgical clips and metal foreign bodies

    Contacts and Locations

    Sponsors and Collaborators AstraZeneca
    Locations
    • Research Site | Duarte, California, United States, 91010
    • Research Site | Atlanta, Georgia, United States, 30322
    • Research Site | Florham Park, New Jersey, United States, 07932
    • Research Site | Salt Lake City, Utah, United States, 84106
    • Research Site | Madison, Wisconsin, United States, 53792
    • Research Site | Ciudad Autónoma de Bs. As., Argentina, 1426
    • Research Site | Ciudad Autónoma de Bs. As., Argentina, C1199ABB
    • Research Site | Mar del Plata, Argentina, 7600
    • Research Site | Rosario, Argentina, 2000
    • Research Site | San Salvador de Jujuy, Argentina, 4600
    • Research Site | Barretos, Brazil, 14784-400
    • Research Site | Curitiba, Brazil, 81520-060
    • Research Site | Florianópolis, Brazil, 88034-000
    • Research Site | Fortaleza, Brazil, 60336-045
    • Research Site | Porto Alegre, Brazil, 90160-093
    • Research Site | Porto Alegre, Brazil, 90610-000
    • Research Site | Ribeirão Preto, Brazil, 14021-636
    • Research Site | Sao Paulo, Brazil, 01221-0100
    • Research Site | São Paulo, Brazil, 01246-000
    • Research Site | Beijing, China, 100021
    • Research Site | Beijing, China, 100730
    • Research Site | Changchun, China, 130000
    • Research Site | Changsha, China, 410013
    • Research Site | Chengdu, China, 610041
    • Research Site | Guangzhou, China, 510100
    • Research Site | Hangzhou, China, 310003
    • Research Site | Hangzhou, China, 310006
    • Research Site | Hangzhou, China, 310022
    • Research Site | Jinan, China, 250117
    • Research Site | Linhai, China, 317000
    • Research Site | Shanghai, China, 200030
    • Research Site | Shanghai, China, 200032
    • Research Site | Urumqi, China, 830099
    • Research Site | Wuhan, China, 430022
    • Research Site | Wuhan, China, 430030
    • Research Site | Budapest, Hungary, 1083
    • Research Site | Budapest, Hungary, 1121
    • Research Site | Gyöngyös - Mátraháza, Hungary, 3200
    • Research Site | Pécs, Hungary, 7623
    • Research Site | Bangalore, India, 560068
    • Research Site | Gurgaon, India, 122001
    • Research Site | Hubli, India, 580025
    • Research Site | Karamsad, India, 388325
    • Research Site | Kolkata, India, 700160
    • Research Site | Nashik, India, 422002
    • Research Site | New Delhi, India, 110063
    • Research Site | New Delhi, India, 110085
    • Research Site | New Delhi, India, 11029
    • Research Site | Hiroshima-shi, Japan, 734-8551
    • Research Site | Kanazawa-shi, Japan, 920-8641
    • Research Site | Kashiwa, Japan, 227-8577
    • Research Site | Nagoya-shi, Japan, 460-0001
    • Research Site | Niigata-shi, Japan, 951-8566
    • Research Site | Osaka-shi, Japan, 541-8567
    • Research Site | Osakasayama, Japan, 589-8511
    • Research Site | Sakai-shi, Japan, 591-8555
    • Research Site | Sapporo-shi, Japan, 003-0804
    • Research Site | Sendai-shi, Japan, 980-0873
    • Research Site | Shinjuku-ku, Japan, 160-0023
    • Research Site | Sunto-gun, Japan, 411-8777
    • Research Site | Yokohama-shi, Japan, 241-8515
    • Research Site | Cheongju-si, Korea, Republic of, 28644
    • Research Site | Incheon, Korea, Republic of, 21565
    • Research Site | Seongnam-si, Korea, Republic of, 13620
    • Research Site | Seoul, Korea, Republic of, 05505
    • Research Site | Seoul, Korea, Republic of, 06351
    • Research Site | George Town, Malaysia, 10450
    • Research Site | Kuala Lumpur, Malaysia, 59100
    • Research Site | Selangor, Malaysia, 46050
    • Research Site | Mérida, Mexico, 97134
    • Research Site | Lima, Peru, LIMA 31
    • Research Site | Lima, Peru, Lima 32
    • Research Site | Lima, Peru, LIMA 34
    • Research Site | Lima, Peru, LIMA 41
    • Research Site | San Isidro, Peru, 27
    • Research Site | Kazan, Russian Federation, 420029
    • Research Site | Kostroma, Russian Federation, 156005
    • Research Site | Moscow, Russian Federation, 121205
    • Research Site | Novisibirsk, Russian Federation, 630082
    • Research Site | Obninsk, Russian Federation, 249036
    • Research Site | Saint-Petersburg, Russian Federation, 197022
    • Research Site | Saint-Petersburg, Russian Federation, 197758
    • Research Site | Ufa, Russian Federation, 450054
    • Research Site | Barcelona, Spain, 08003
    • Research Site | Madrid, Spain, 28040
    • Research Site | Madrid, Spain, 28046
    • Research Site | Málaga, Spain, 29010
    • Research Site | San Sebastián, Spain, 20014
    • Research Site | Sevilla, Spain, 41009
    • Research Site | Valencia, Spain, 46009
    • Research Site | Kaohsiung, Taiwan, 83301
    • Research Site | Taichung City, Taiwan, 402
    • Research Site | Taichung, Taiwan, 40447
    • Research Site | Taichung, Taiwan, 40705
    • Research Site | Tainan City, Taiwan, 70403
    • Research Site | Taipei, Taiwan, 10002
    • Research Site | Taipei, Taiwan, 11217
    • Research Site | Taoyuan, Taiwan, 00333
    • Research Site | Bangkok, Thailand, 10300
    • Research Site | Bangkok, Thailand, 10330
    • Research Site | Bangkok, Thailand, 10400
    • Research Site | Bangkok, Thailand, 10700
    • Research Site | Hat Yai, Thailand, 90110
    • Research Site | Khon Kaen, Thailand, 40002
    • Research Site | Lampang, Thailand, 52000
    • Research Site | Mueang, Thailand, 50200
    • Research Site | Adana, Turkey, 01120
    • Research Site | Adapazari, Turkey, 54290
    • Research Site | Ankara, Turkey, 06280
    • Research Site | Ankara, Turkey, 6200
    • Research Site | Ankara, Turkey,
    • Research Site | Istanbul, Turkey, 34030
    • Research Site | Istanbul, Turkey, 34854
    • Research Site | Izmir, Turkey, 35620
    • Research Site | Hanoi City, Vietnam, 100000
    • Research Site | Hanoi, Vietnam, 100000
    • Research Site | Ho Chi Minh, Vietnam, 700000
    • Research Site | Ho Chi Minh, Vietnam, 70000
    Investigators
    • Principal Investigator: Suresh S Ramalingam, MD, Emory University School of Medicine, Atlanta, U.S.
    • Principal Investigator: Shun Lu, MD, Shanghai Chest Hospital, Shanghai, China

    More Information

    Publications

    Additional Relevant MeSH Terms

    • 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