To assess the efficacy and safety of AZD9291 versus Placebo, in patients with Epidermal Growth Factor Receptor Mutation Positive stage IB-IIIA non-small cell lung carcinoma, following complete tumour resection with or without adjuvant chemotherapy
This is a phase 3 double-blind, randomized, placebo-controlled, study to assess the efficacy and safety of AZD9291 versus placebo in patients with stage IB-IIIA non-small cell lung cancer (NSCLC) with centrally confirmed, most common sensitising EGFR mutations (Ex19Del and L858R) either alone or in combination with other EGFR mutations as confirmed by a central test, who have had complete tumour resection, with or without postoperative adjuvant chemotherapy. Adjuvant chemotherapy should have consisted of a platinum based doublet given for a maximum of 4 cycles.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
682
The initial dose of AZD9291 80 mg once daily can be reduced to 40 mg once daily.
The initial dose of Placebo AZD9291 80 mg once daily can be reduced to 40 mg once daily.
Eligible patients will be offered open-label osimertinib upon recurrence and in the absence of intervening systemic anti-cancer therapy.
Assess the Efficacy of AZD9291 Compared to Placebo as Measured by Disease Free Survival (DFS).
Defined as the time from the date of randomization until the date of disease recurrence or death (by any cause in the absence of recurrence).
Time frame: Up to approximately 5 years after the first patient is randomized (maximum follow up of 70 months)
Disease Free Survival (DFS) Rate at 2, 3 and 5 Years
Defined as the percentage of patients alive and disease free at 2, 3 and 5 years, respectively, estimated from Kaplan Meier plots of the primary endpoint of DFS.
Time frame: Up to approximately 5 years after the first patient is randomized (maximum follow up of 70 months). DFS rate at 2 years (%), 3 years (%) and 5 years (%) are presented.
Overall Survival (OS)
Defined as the time from the date of randomization until date of death due to any cause.
Time frame: Up to approximately 7 years after the first patient is randomized (maximum follow up of 86 months)
Overall Survival Rate at 2, 3 and 5 Years
Defined as the percentage of patients alive at 2, 3 and 5 years, respectively, estimated from a Kaplan Meier plot of OS.
Time frame: Up to approximately 7 years after the first patient is randomized (maximum follow up of 86 months). OS rate at 2 years (%), 3 years (%) and 5 years (%) are presented.
Patient Health-related Quality of Life and Symptoms (HRQoL) by SF-36v2 Health Survey.
Change from baseline will be calculated for each domain and summary scale at each scheduled post-baseline assessment. The SF-36 includes eight domains: Physical Functioning (PF); Role Limitations-Physical (RP), Vitality (VT), General Health Perceptions (GH), Bodily Pain (BP), Social Function (SF), Role Limitations-Emotional (RE), and Mental Health (MH) and two summary scores: The Physical Component Summary (PCS) and Mental Component Summary (MCS). Final scores for each scale range from 0-100 with higher scores indicating better health.
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Research Site
Los Angeles, California, United States
Research Site
Santa Monica, California, United States
Research Site
Santa Rosa, California, United States
Research Site
Torrance, California, United States
Research Site
Grand Junction, Colorado, United States
Research Site
New Haven, Connecticut, United States
Research Site
Norwalk, Connecticut, United States
Research Site
Fort Myers, Florida, United States
Research Site
Pembroke Pines, Florida, United States
Research Site
St. Petersburg, Florida, United States
...and 228 more locations
Time frame: Measured by SF-36 Questionnaire at baseline, 12 week, 24 week and then every 24 weeks until study complete, disease recurrence or other discontinuation criteria met, up to 3 years.
Plasma Concentrations of AZD9291
The pharmacokinetics exposure parameters derived from plasma concentrations of AZD9291
Time frame: Collected at pre-dose, 0.5-1.5hours and 2-4hours post-dose up to 96 weeks (approximately 24 months)
Plasma Concentrations of AZ5104 Metabolites
The pharmacokinetics exposure parameters derived from plasma concentrations of AZ5104 metabolites
Time frame: From date of dosing to week 96 (approximately 24 months)
Plasma Concentrations of AZ7550 Metabolites
The pharmacokinetics exposure parameters derived from plasma concentrations of AZ7550 metabolites
Time frame: From date of dosing to week 96 (approximately 24 months)