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 July 23, 2024. Link to the current ClinicalTrials.gov record.Recruitment Status
ACTIVE, NOT RECRUITING (See Contacts and Locations)Verified July 2024 by AstraZeneca
Sponsor
AstraZenecaInformation Provided by (Responsible Party)
AstraZenecaClinicaltrials.gov Identifier
NCT03521154Other Study ID Numbers: D5160C00048
First Submitted: April 20, 2018
First Posted: May 11, 2018
Last Update Posted: July 24, 2024
Last Verified: July 2024
History of Changes
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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 |
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Study Design
| Study Type | Interventional |
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| Actual Enrollment | 216 participants |
| Design Allocation | Randomized |
| Interventional Model | Parallel Assignment |
| Masking | Double |
| Primary Purpose | Treatment |
| Official Title | 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). |
| Study Start Date | July 19, 2018 |
| Actual Primary Completion Date | January 5, 2024 |
| Anticipated Study Completion Date | June 29, 2026 |
Groups and Cohorts
| Group/ Cohort | Intervention/ Treatment |
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Outcome Measures
Primary Outcome Measures
- 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
- 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
- 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
- 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
- Overall survival (OS) [Approximately 45 months] Defined as the time from randomization until death from any cause
- 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
- 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
- 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
- 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
- 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
- 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
- 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.
- 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
- 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.
- Patients reported disease-related symptoms and HRQoL by EORTC QLQ-LC13 and EORTC QLQ-30 questionnaires [Approximately 21 months] Change in symptoms from baseline
- Incidence of Adverse Events (AEs) [Approximately 13 months] AEs graded by CTCAE version 5.0
- 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) |
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| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | No |
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Contacts and Locations
| Sponsors and Collaborators | AstraZeneca |
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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