A Global Study to Assess the Effects of Osimertinib Following Chemoradiation in Patients With Stage III Unresectable Non-small Cell Lung Cancer (LAURA)
- Conditions
- Non Small Cell Lung Cancer (Stage III)
- Interventions
- Drug: Placebo Osimertinib 80mg/40mg
- Registration Number
- NCT03521154
- Lead Sponsor
- AstraZeneca
- Brief Summary
A global study to assess the efficacy and safety of osimertinib following chemoradiation in patients with stage III unresectable Epidermal Growth Factor Receptor Mutation Positive non-small cell lung cancer
- Detailed 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 216
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Osimertinib Osimertinib 80mg/40mg Osimertinib (80mg or 40mg orally, once daily), in accordance with the randomization schedule. Placebo Osimertinib Placebo Osimertinib 80mg/40mg Matching placebo for Osimertinib (80mg or 40mg orally, once daily), in accordance with the randomization schedule
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) by Blinded Independent Central Review (BICR) Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months 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 BICR assessment according to RECIST v1.1
- Secondary Outcome Measures
Name Time Method Number of Participants With Progression-free Survival (PFS) Events in Patients With EGFR Ex19del or L858R Mutation Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months Number of PFS events (PFS is 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 BICR assessment according to RECIST v1.1)
Number of Participants With Progression-free Survival (PFS) Events in Patients With EGFR Mutations Ex19del or L858R Detectable in Plasma-derived ctDNA Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months Number of PFS events (PFS is 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 (BICR) assessment according to RECIST v1.1)
Central Nervous System (CNS) Progression-free Survival (PFS) by Blinded Independent Central Review (BICR) Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months Time from randomisation until the date of CNS disease progression or death (by any cause in the absence of CNS progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression, based on CNS BICR assessment according to RECIST v1.1
Overall Survival (Count) Date of randomisation to date of death by any cause. Assessed up to a maximum of approximately 63 months Number of patients with Overall Survival (OS), the time from the date of randomisation until date of death by any cause
Overall Survival (Duration) Date of randomisation to date of death by any cause. Assessed up to a maximum of approximately 63 months Time from the date of randomisation until death by any cause
Objective Response Rate by Blinded Independent Central Review (BICR) Every 8 weeks for first 48 weeks, then every 12 weeks until radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months Percentage of evaluable patients with at least one BICR assessed visit response of complete response (CR) or partial response (PR). CR defined as disappearance of all target lesions (TL) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10mm. PR defined as \>= 30% decrease in the sum of diameters of target lesions (compared to baseline sum of diameters). Responses include both confirmed and unconfirmed BICR responses
Duration of Response, Unconfirmed by Blinded Independent Central Review (BICR) Every 8 weeks for first 48 weeks, then every 12 weeks until radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months Date of PFS event - date of first unconfirmed response + 1 day (and expressed in months) for unconfirmed responses only
Disease Control Rate by Blinded Independent Central Review (BICR) Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months Percentage of patients who have a best overall response of complete response (CR), partial response (PR) or stable disease (SD) as assessed by BICR
Tumour Shrinkage by Blinded Independent Central Review (BICR) Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months Depth of response (or tumour shrinkage or change in tumour size) was assessed using BICR responses in target lesions. The best change in tumour size is the largest decrease from baseline or the smallest increase from baseline in the absence of a reduction
Proportion With Tumour Shrinkage by Blinded Independent Central Review (BICR) Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months Proportion with depth of response (or tumour shrinkage or change in tumour size)
Time to Death or Distant Metastases by Blinded Independent Central Review (BICR) Time from randomisation to the date of distant metastases or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months Time from the date of randomisation until the first date of distant metastases or date of death in the absence of distant metastasis. Distant metastasis is defined as any new lesion that is detected on a scan that is anywhere other than lung or regional lymph node according to RECIST v1.1 or proven by biopsy
Time to Study Treatment Discontinuation Time from randomisation to the earlier of the date of study treatment discontinuation or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months Time from randomisation to the earlier of the date of study treatment discontinuation (regardless of the reason for study treatment discontinuation) or death (i.e. date of study treatment discontinuation/death or censoring - date of randomisation + 1 day, expressed in months)
Time to First Subsequent Treatment Time from randomisation to the start of first subsequent anti-cancer therapy or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months Time from the date of randomisation to the earlier of the date of anti-cancer therapy start date following study drug discontinuation or death
Time to Second Subsequent Treatment Time from randomisation to the start of second subsequent anti-cancer therapy or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months Time from the date of randomisation to the earlier of the second subsequent anti-cancer therapy start date following study drug discontinuation or death
Second Progression-free Survival (PFS2) Every 8 weeks for first 48 weeks, then every 12 weeks. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months Time from randomisation to the earliest progression event following first objective disease progression, subsequent to the first subsequent therapy, or death.
Trial Locations
- Locations (1)
Research Site
🇻🇳Ho Chi Minh, Vietnam