Subjects with EGFRm+/T790M, locally advanced or metastatic NSCLC who have progressed following prior therapy with an approved EGFR-TKI MedDRA version: 20.0 Level: PT Classification code 10062042 Term: Lung neoplasm System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: AZD9291
Pharmaceutical Form: Capsule, hard
Current Sponsor code: AZD9291 MESYLATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 80-
Sponsors
ASSOCIAZIONE PIEMONTESE DI ONCOLOGIA TORACICA (APOT)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent prior to any study specific procedures. 2. Male or female, aged at least 18 years. 3. Histological or cytological confirmation diagnosis of NSCLC. 4. Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy (IIIB and IV stages, according to the UICC TNM 7th edition) 5. Radiological documentation of disease progression after a previous continuous treatment with a EGFR-TKI (e. g. Gefitinib, Erlotinib, Afatinib). In addition other lines of therapy may have been given. All patients must have documented radiological progression after the last treatment administered prior to enrolling in the study. 6. Patients must fulfil one of the following: • Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) • OR • Must have experienced clinical benefit from EGFR-TKI, according to the Jackman criteri (Jackman et al 2010) followed by systemic objective progression (RECIST or WHO) while on continuous treatment with EGFR TKI 7. Patients must have confirmation of tumour T790M mutation positive status from a biopsy sample taken after confirmation of disease progression on treatment with EGFR-TKI. Biopsy samples will be locally analysed. 8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks. 9. At least one lesion (measurable and/or non-measurable) that can be accurately assessed by CT or MRI at baseline and follow up visits. 10. Patients must have adequate verbal comprehension skills for answering to the surveys provided by the investigator during the study. 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 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Involvement in the planning and/or conduct of the study (applies to both Sponsor staff and/or staff at the study site). 2. Concrete possibility to be enrolled in any of the other ongoing clinical studies with AZD9291 (http://www.cancer.gov). The study will enroll patients recorded as screening failure in AURA-3 and CAURAL or not fulfilling inclusion/exclusion criteria ab initio or with a poor tumor sample not suitable for central analysis. 3. Treatment with any of the following: • Treatment with an EGFR-TKI (e.g., erlotinib, gefitinib, or afatinib) within 8 days or approximately 5x half-life, whichever is the longer, of the first dose of study treatment. (If sufficient washout time has not occurred due to schedule or PK properties, an alternative appropriate washout time based on known duration and time to reversibility of drug related adverse events could be agreed upon by the Sponsor and the Investigator). • Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment • Previous treatment with AZD9291, or a 3rd generation EGFR TKIs (e.g., CO-1686) • Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment • Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study treatment 4. Patients currently receiving (or unable to stop use at least 1 week prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inhibitors of CYP2C8 and potent inhibitors or inducers of CYP3A4 5. Treatment with an investigational drug within five half-lives of the compound 6. Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior platinum-therapy related neuropathy. 7. Spinal cord compression or brain metastases unless asymptomatic, stable and not requiring steroids for at least 4 weeks prior to start of study treatment. 8. 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. 9. Any of the following cardiac criteria: • Mean resting corrected QT interval (QTc) > 470 msec, obtained from 3 electrocardiograms (ECGs). • Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval >250msec. • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval. 10. 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. 11. History of hypersensitivity to active or inactive excipients of AZD9291 or drugs with a similar chemical structure or class to AZD9291.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the tolerability of AZD9291 when given orally to a real life population of patients with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC), who have progressed after prior therapy with an Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) agent.;Secondary Objective: To evaluate patients' perception of symptomatic Adverse Events (AEs) when under continuous treatment with AZD9291, and to compare it to physicians evaluation, being the medical evaluation performed according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. To assess changes in Quality of life, depression, sleep quality and distress of advanced NSCLC patients undergoing continuous treatment with AZD9291. To further investigate the anti tumour activity of AZD9291 by evaluation of duration of response, disease control rate, tumour shrinkage, progression free survival (PFS) using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, through local review of radiological examinations performed during the study. ;Primary end point(s): To investigate the tolerability of AZD9291 when given orally to a real life population of patients with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC), who have progressed after prior therapy with an Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) agent.;Timepoint(s) of evaluation of this end point: 4 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To evaluate patients' perception of symptomatic Adverse Events (AEs) when under continuous treatment with AZD9291, and to compare it to physicians evaluation, being the medical evaluation performed according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.;Timepoint(s) of evaluation of this end point: 4 years | — |
Countries
Italy
Contacts
Public ContactSCDU Malattie dell'apparato respira
AOU San Luigi Gonzaga
Outcome results
None listed