Patients with NSCLC
Conditions
Interventions
Trade Name: Tagrisso
Product Name: Tagrisso
Product Code: AZD9291
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: OSIMERTINIB
CAS Number: 1421373-66-1
Current Sponsor code: AZD9291 mesyla
Sponsors
Hellenic Oncology Research Group
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For inclusion in the study subjects should fulfill the following criteria: 1. Age >18 years 2. Both sexes 3. Histologically or cytologically documented NSCLC 4. Stage IIIB not amenable to radical therapy or stage IV 5. Presence of EGFR activating mutations (exon 19 deletion or L858R in exon 21) 6. First or second line treatment with EGFR TKIs 7. Performance status (ECOG): 0-1 8. Measurable or evaluable disease 9. Adequate organ function tests (Hb=10g/dL, WBC=3.0 x 109/L , neutrophils count=1.5 x 109/L, platelets=100 x 109/L, Creatinine clearance=50 mL/min, Total bilirubin=1.5 X UNL, AST, ALT and ALP=2.5 x UNL) 10. Normal QT interval in ECG 11. CNS metastases are allowed provided that they have been irradiated and the patient is clinically stable 12. Women of child bearing potential and all men will be required to use adequate contraceptive measures 13. Life expectancy of at least 3 months 14. Written informed consent 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 48 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects should not enter the study if any of the following exclusion criteria are fulfilled: 1. History of serious drug allergy 2. Refractory nausea, vomiting and chronic gastrointestinal diseases 3. 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. 4. Severe or uncontrolled systemic liver disease, including those with known hepatitis B, hepatitis C, and Human Immunodeficiency virus (HIV) infection 5. Interstitial lung disease or pulmonary fibrosis 6. Pregnancy, lactation or other concomitant serious medical condition 7. Other concurrent active malignancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To identify biomarkers, exploiting the longitudinal analysis of tumor-derived plasma/serum DNA and CTCs, of primary and/or secondary resistance to first and third (AZD9291) generation EGFR TKIs.;Secondary Objective: To (i) investigate the effect of first and third (AZD9291) generation EGFR TKIs on the elimination of specific plasma tumor-derived mutations and T790M (+) CTCs; (ii) explore the clinical usefulness of qualitative and quantitative monitoring of serum/plasma EGFR mutation status and molecular/phenotypic changes of CTCs during treatment; (iii) investigate novel mechanisms associated with primary and/or secondary resistance to anti- EGFR TKIs by performing targeted EGFR gene sequence in the ctDNA and (iv) evaluate the efficacy and tolerance of AZD9291 in patients with EGFR-mut NSCLC resistant to first generation EGFR TKIs.;Primary end point(s): To identify biomarkers, exploiting the longitudinal analysis of tumor-derived plasma/serum DNA and CTCs, of primary and/or secondary resistance to first and third (AZD9291) generation EGFR TKIs.;Timepoint(s) of evaluation of this end point: At the end of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To (i) investigate the effect of first and third (AZD9291) generation EGFR TKIs on the elimination of specific plasma tumor-derived mutations and T790M (+) CTCs; (ii) explore the clinical usefulness of qualitative and quantitative monitoring of serum/plasma EGFR mutation status and molecular/phenotypic changes of CTCs during treatment; (iii) investigate novel mechanisms associated with primary and/or secondary resistance to anti- EGFR TKIs by performing targeted EGFR gene sequence in the ctDNA and (iv) evaluate the efficacy and tolerance of AZD9291 in patients with EGFR-mut NSCLC resistant to first generation EGFR TKIs.;Timepoint(s) of evaluation of this end point: At the end of the study | — |
Countries
Greece
Contacts
Public ContactIoannis Athanasakis
Hellenic Oncology Research Group
Outcome results
None listed