Stage IB-IIIA non-small cell lung carcinoma, with a centrally confirmed, common sensitising EGFR mutations (Ex19del and L858R either alone or in combination with other EGFR mutations), following complete tumour resection with or without adjuvant chemotherapy MedDRA version: 20.0 Level: PT Classification code 10029520 Term: Non-small cell lung cancer stage IIIA System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Class
Conditions
Interventions
Trade Name: Tagrisso (osimertinib)
Product Name: AZD9291 80 mg film-coated tablet
Product Code: AZD9291
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Osimertinib
CAS Number: 1421373-66
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female, aged at least 18 years. 2. Histologically confirmed diagnosis of primary non small lung cancer (NSCLC) on predominantly non-squamous histology 3. MRI or CT scan of the brain must be done prior to surgery as it is considered standard of care. 4. Patients must be classified post-operatively as Stage IB, II or IIIA on the basis of pathologic criteria. 5. 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. 6. 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. 7. Complete recovery from surgery and standard post-operative therapy (if applicable) at the time of randomization. 8. World Health Organization Performance Status of 0 to 1. 9. 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 322 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 378
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 CYP3A4 - 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 |
|---|---|
| Main Objective: To assess the efficacy of AZD9291 compared to placebo as measured by disease free survival (DFS);Secondary Objective: 1) To further assess the efficacy of AZD9291 compared with placebo by assessment of DFS rate at 2 years, 3 years and 5 years, of OS and OS rate at 5 years 2) To assess the effect of AZD9291 compared with placebo on health-related quality of life (HRQoL) by assessment of patient health-related quality of life and symptoms (HRQoL) using SF-36 questionnaire (version 2) 3) To characterise the pharmacokinetics (PK) of AZD9291 and its metabolites (AZ5104 and AZ7550) by assessment of PK exposure parameters derived from plasma concentrations of AZD9291 and metabolites AZ5104 and AZ7550. 4) To assess the safety and tolerability profile of AZD9291 compared with placebo by assessment of number and severity of adverse events, clinical chemistry, haematology, urinalysis, vital signs, physical examination, body weight, digital electrocardiogram (ECG), left Ventricular Ejection Fraction (LVEF), World Health Organization (WHO) Performance Status and Ophthalmologic assessment ;Primary end point(s): Disease free survival (DFS) using investigator assessments;Timepoint(s) of evaluation of this end point: At baseline and from randomization until recurrence | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Assessment of Disease free survival (DFS) rate at 2 years, 3 years and 5 years 2) Analysis of Overall Survival (OS) 3) Assessment of Overall Survival (OS) rate at 5 years 4) Assessing of patient health-related quality of life and symptoms (HRQoL) using SF-36 questionnaire (version 2, standard) 5) PK exposure parameters derived from plasma concentrations of AZD9291 and metabolites AZ5104 and AZ7550. Pharmacokinetics data from this study will be analysed using a population PK approach and may also form part of a pooled analysis with other AZD9291 studies; results from these analyses will be reported separately from the CSR 6) Safety and tolerability endpoints assessed by number and severity of adverse events, clinical chemistry, haematology, urinalysis, vital signs, physical examination, body weight, digital electrocardiogram (ECG), left Ventricular Ejection Fraction (LVEF), World Health Organization (WHO) Performance Status and Ophthalmologic assessment ;Timepoint(s) of evaluation of this end point: Throughout the trial | — |
Countries
Australia, Belgium, Brazil, Canada, China, France, Germany, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Romania, Russian Federation, Spain, Sweden, Taiwan, Thailand, Turkey, Ukraine, United States, Vietnam
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed