Stage IB-IIIA Non-small Cell Lung Carcinoma
Conditions
Interventions
investigational material(s)
Generic name etc : AZD9291 80mg/40mg
INN of investigational material : -
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigationa
Sponsors
Astrazeneca K.K
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed diagnosis of primary non small lung cancer (NSCLC) on predominantly non-squamous histology. 2. MRI or CT scan of the brain must be done prior to surgery as it is considered standard of care. 3. Patients must be classified post-operatively as Stage IB, II or IIIA on the basis of pathologic criteria. In Japan, patients with Stage IB disease are not eligible. 4. Confirmation by the central laboratory that the tumour 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 including T790M. 5. Complete surgical resection of the primary NSCLC is mandatory. All gross disease must have been removed at the end of surgery. All surgical margins of resection must be negative for tumour. 6. Complete recovery from surgery and standard post-operative therapy (if applicable) at the time of randomization. 7. World Health Organization Performance Status of 0 to 1. 8. Female patients should be using adequate contraceptive measures, should 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-child-bearing potential. 18 Years and older, Patients from Japan aged at least 20 years
Exclusion criteria
Exclusion criteria: 1. Treatment with any of the following: - Pre-operative or post-operative or planned radiation therapy for the current lung cancer - Pre-operative (neo-adjuvant) platinum based or other chemotherapy - Any prior anticancer therapy - Prior treatment with neoadjuvant or adjuvant EGFR-TKI at any time - Major surgery (including primary tumour surgery, excluding placement of vascular access) within 4 weeks of the first dose of study drug - Patients currently receiving medications or herbal supplements known to be potent inducers of cytochrome P450 (CYP) 3A4 - Treatment with an investigational drug within five half-lives of the compound or any of its related material. 2. Patients who have had only segmentectomies or wedge resections. 3. History of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, or other solid tumours curatively treated with no evidence of disease for > 5 years following the end of treatment. 4. Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy. 5. 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). 6. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of AZD9291. 7. Any of the following cardiac criteria: - Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTc value. - Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG. - Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval. 8. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD. 9. Inadequate bone marrow reserve or organ function.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Assess the Efficacy of AZD9291 Compared to Placebo as Measured by Disease Free Survival (DFS). [ Time Frame: Up to approximately 5 years after the first patient is randomized (maximum follow up of 70 months) ] 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). | — |
Secondary
| Measure | Time frame |
|---|---|
| - Disease Free Survival (DFS) Rate at 2, 3 and 5 Years [ 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. ] 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. - Overall Survival (OS) [ Time Frame: Up to approximately 7 years after the first patient is randomized (maximum follow up of 86 months) ] Defined as the time from the date of randomization until date of death due to any cause. - Overall Survival Rate at 2, 3 and 5 Years [ 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. ] Defined as the percentage of patients alive at 2, 3 and 5 years, respectively, estimated from a Kaplan Meier plot of OS. - Patient Health-related Quality of Life and Symptoms (HRQoL) by SF-36v2 Health Survey. [ 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. ] 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. - 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) ] The pharmacokinetics exposure parameters | — |
Countries
Australia, Belgium, Brazil, Canada, China, France, Germany, Hong Kong, Hungary, Israel, Italy, Netherlands, Norway, Poland, Romania, Russian Fenderation, South Korea, Spain, Sweden, United States
Contacts
Public ContactKazushige Hibi
Astrazeneka K.K
Outcome results
None listed