Non-Small Cell Lung Cancer MedDRA version: 18.0 Level: PT Classification code 10029515 Term: Non-small cell lung cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: AZD9291 40 film-coated tablet
Product Code: AZD9291
Pharmaceutical Form: Tablet
INN or Proposed INN: Not yet assigned
CAS
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses - Aged at least 18 years. Patients from Japan aged at least 20 years. - Histological or cytological confirmation diagnosis of Non Small Cell Lung Cancer (NSCLC). -Radiological documentation of disease progression while on a previous continuous treatment with an EGFR TKI e.g. gefitinib or erlotinib (with the exception of 1st line expansion cohort). In addition other lines of therapy may have been given. - Previous treatment with a single-agent EGFR TKI (e.g. gefitinib or erlotinib). - Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing or evidence of non-child bearing potential. - Male patients should be willing to use barrier contraception. - For 1st Line expansion cohort ONLY, confirmation that the tumour is EGFRm+ve and have had no prior therapy for their advanced disease. 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 175 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
Exclusion criteria: Treatment with an EGFR TKI (erlotinib or gefitinib) within 8 days (approximately 5x half-life) of the first dose of study treatment. - Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from the treatment of advanced NSCLC from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment. - AZD9291 in the present study (ie, dosing with AZD9291 previously initiated in this study). - Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection. - Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: -Adverse events will be collected from baseline until 28 days after the last dose, expected average 6 months ORR 6 weekly until progression ;Main Objective: To investigate the safety, tolerability and efficacy (Objective Response Rate) of AZD9291 when given orally to patients with locally advanced or metastatic Non Small Cell Lung Cancer (NSCLC) who have progressed following prior therapy with an Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) agent.; Secondary Objective: Define maximum tolerated dose (MTD), a dose/exposure to result in biological activity (incl but not limited to RECIST, tumour & blood borne biomarkers) or max feasible dose Investigate safety & tolerability of oral AZD9291 - 1st line therapy to patients (treatment-naive) - locally advanced or metastatic EGFRm+ve NSCLC. Characterise PK of AZD9291 & metabolites (AZ5104, AZ7550) - single oral dose, steady state multiple doses. Escalation &expansion cohorts: Obtain assessment anti-tumour activity of AZD9291 by evaluation of DoR & PFS by Response Evaluation Criteria in Solid Tumours (RECIST) Extension cohort: Additional assessments of anti tumour activity of AZD9291 by evaluation :duration of response, disease control rate, tumour shrinkage, PFS using Response Evaluation Criteria in Solid Tumours (RECIST) assessed by independent central review of radiological information & overall survival. Assess relationship of PK & selected efficacy, pharmacodynamic and/or safety endpoints. ;Primary end point(s): Safety, tolerability and efficacy (ORR) of AZD9291, as assessed by number and severity of adverse events as recorded on the case report form, vital signs, laboratory variables, physical examination, electrocardiogram and ophthalmic examinations and RECIST1.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Plasma concentrations of AZD9291 & 2 active metabolites (AZ5104, AZ7550) & pharmacokinetic parameters following single dose (Cmax, tmax, AUC, terminal rate constant, clearance, half life, volume of distribution & mean resistance time) -Plasma concentrations of AZD9291 & 2 active metabolites (AZ5104,AZ7550) and pharmacokinetic parameters following dosing with AZD9291 (Cmax, tmax, AUC, terminal rate constant, clearance, half life, volume of distribution and mean resistance time) -Plasma concentrations of AZD9291 & 2 active metabolites (AZ5104, AZ7550) and pharmacokinetic parameters following multiple doses (steady state Cmax, tmax, Cmin AUC, clearance, accumulation ratio and time dependency) -Pharmacodynamic markers to assess correlations with disease activity, effects of study drug & clinical outcomes -Pharmacodynamic markers to assess correlations with disease activity, effects of study drug & clinical outcomes -Evaluation of tumour response, duration of response, tumour shrinkage, progression free survival and overall survival as assessed by RECIST 1.1 -Pharmacodynamic markers in EGFRm+ T790M+ tumours at selective endpoints -Patient reported outcomes: EORTC QLQ C-30 and QLQ-LC13 -Pharmacogenetics ; Timepoint(s) of evaluation of this end point: Single dose PK day 1, PK & metabolites Cycle 1 day 15 Multiple dose PK & metabolites Cycle 1 (pre-dose day 1,8 & 15) Cycle 2 (pre-dose & 1,1.5,2,4,6,8,10,12,24 hours post dose). Pharmacodynamics -optional tumour biopsy - screening, day 15, discontinuation -plasma for circulating free tumour DNA - screening day 1 (dosing), 6 weekly, discontinuation, 28 days after last dose & disease progression or withdrawal from study Pharmacodynamic markers - optional | — |
Countries
Australia, France, Germany, Italy, Japan, Korea, Republic of, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactInformation Center
Astrazeneca
Outcome results
None listed