Patients diagnosed with stage IIIB or IV non-small cell lung cancer carrying the EGFR activating mutation and confirming concomitant T790M mutation during screening who have not received prior treatment for this advanced disease will be enrolled in this study. Patients are not eligible if they are candidates for local curative treatment. MedDRA version: 19.0 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignan
Conditions
Interventions
Trade Name: TAGRISSO
Product Name: TAGRISSO
Product Code: EU/1/16/1086/001
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ND
CAS Number: ND
Current Sponsor code: AZD9291
Other descriptiv
Sponsors
Medica Scientia Innovation Research (MedSIR ARO)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria 1. Patient aged 18 years or older. 2. Patients with histological confirmation of locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) with an activating EGFR mutation and concomitant T790M mutation who are not candidates for local curative treatment. 3. Patients with a M1a stage according to the TNM version 7 including M1a (malignant effusion) or M1b (distant metastasis), or locally advanced disease for which there is no curative treatment (including patients who progress after chemoradiotherapy in stage III disease). 4. Patients with a EGFR deletion or mutation in exon 19, exon 21 (L858R, L861Q) or exon 18 (G719X) and concomitant T790M mutation before treatment confirmed centrally. 5. ECOG (Eastern Cooperative Oncology Group) performance status less than or equal to 2. 6. Existence of measurable or evaluable disease (as per RECIST 1.1 criteria). Patients with asymptomatic and stable brain metastases are eligible for the study. 7. Possibility of obtaining sufficient tissue sample, via a biopsy or surgical resection of the primary tumor or metastatic tumor tissue, within the 60 days prior to study entry. 8. Life expectancy =12 weeks. 9. Adequate hematologic function: Absolute neutrophil count (ANC) > 1.5 x 109/L, platelet count > 100.0 x109/L and hemoglobin > 9.0 g/dL (> 6.2 mmol/L). 10. Adequate coagulation: INR = 1.5. 11. Adequate liver function: Total bilirubin 50 mL/min (Cockroft-Gault) and proteinuria =65 years) yes F.1.3.1 Number of subjects for this age range 73
Exclusion criteria
Exclusion criteria: Any patient meeting ANY of the following criteria will be excluded from the study: 1. Locally advanced lung cancer candidate for curative treatment through radical surgery and/or radio(chemo)therapy. 2. Patients diagnosed with another lung cancer subtype, patients with mixed NSCLC with predominantly squamous cell cancer, or with any small-cell lung cancer component. 3. Patients with a EGFR deletion or mutation in exon 19, exon 21 (L858R, L861Q) or exon 18 (G719X) and concomitant T790M mutation before treatment that have not been confirmed centrally. 4. Patients who have received prior antineoplastic treatment for advanced disease. 5. Second active neoplasia; e.g. patients diagnosed with a potentially lethal cancer for which they may be receiving treatment (but are not obliged to do so). 6. Patients with just one measurable or evaluable tumor lesion that has been resected or irradiated prior to their enrollment in the study. 7. Medical history of Interstitial Lung Disease (ILD) induced by drugs, radiation pneumonitis requiring steroid treatment or any evidence of clinically active ILD. 8. Any of the following criteria: • Corrected QT Interval (QTc) >470 msec, obtained from 3 ECGs at rest, using the QTc value determined according to the clinical screening ECG machine. • Any clinically significant abnormality in ECG rhythm, conduction or morphology at rest. • Any factor that increases the risk of QTc prolongation or risk of irregular heartbeat or sudden inexplicable death under the age of 40 in first-degree relatives or any concomitant medications that prolong the QT interval. 9. Uncontrolled, active or symptomatic metastases of CNS, carcinomatous meningitis or leptomeningeal disease indicated by known clinical symptoms, cerebral edema and/or progressive neoplasia. Patients with history of CNS metastasis or compression of the spinal cord are eligible if they have received local final treatment (e.g., radiotherapy, stereotactic surgery) and if they have remained clinically stable without using anticonvulsants and corticosteroids for a minimum of 4 weeks prior to the first day of study treatment. 10. Refractory nauseas and vomiting, chronic gastrointestinal disease, inability to swallow study drug or significant intestinal resection that restricts the adequate absorption of osimertinib (AZD9291). 11. Patients who have had a surgical procedure unrelated to the study within 7 days prior to the administration of the drug or a significant traumatic lesion during the 4 weeks prior to starting the administration of the study drug, patients who have not recovered from the side effects of any major surgery or patients who might need major surgery during the course of the study. 12. Pregnant or breastfeeding women. Women of childbearing potential, including women who had their last menstrual period within the last two years, must have a negative serum or urine pregnancy test in the 7 days prior to the start of the treatment. 13. Patients who are not willing to use an adequate contraception method until 12 months after the last dose of study treatment. 14. Patients with a serious concomitant systemic disorder (e.g., active infection, including HIV or heart disease) that is incompatible with the study (in the opinion of the investigator), history of bleeding diathesis or anticoagulant therapy (the use of low molecular weight heparin is permitted provided that it is used for prophylaxis). 15. Inability to swallow tablets. 16. Patients with a history of
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of osimertinib (AZD9291), in terms of the objective response rate in patients with advanced non-squamous NSCLC with EGFR mutations and the EGFR T790M mutation at diagnosis as defined by RECIST 1.1 criteria.;Secondary Objective: Determine the safety and tolerability profile of osimertinib (AZD9291) Determine other efficacy parameters such as progression-free survival (PFS), overall survival (OS), time to treatment failure (TTF), duration of response (DOR), disease control rate (DCR), and tumor shrinkage (TS). Correlate the parameters of clinical response efficacy documented with the EGFR mutational status. Carry out a longitudinal analysis of EGFR mutations (including the T790M mutation) in plasma and serum. Determine levels of BIM mRNA as well as mRNA levels of other biomarkers related to EGFR TKI response and determine whether they are predictors of treatment response. To identify mechanisms of acquired resistance to osimertinib (AZD9291); mutations at the site of covalent binding to the drug (C797) or other mutations in tissue or blood. To analyze biomarkers related to mechanisms of resistance to the treatment.;Primary end point(s): The primary endpoint of this study is the objective response rate (ORR) which is defined as the rate of complete responses [CR] or partial responses [PR] to treatment in accordance to the guidelines of RECIST version 1.1 criteria.;Timepoint(s) of evaluation of this end point: An objective response should be confirmed at least 4-6 weeks after the initial response | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Adverse events will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) of the US National Cancer Institute (NCI), version 4 [1]. Grade 3 or 4 adverse events and serious adverse events will be assessed to determine the safety and tolerability of the various combinations of drugs. Secondary endpoints Efficacy Progression-free survival (PFS), overall survival (OS), time to treatment failure (TTF), duration of response (DOR), disease control rate (DCR) and tumor shrinkage (TS) will be determined. PFS is defined as the time from treatment start to death or disease progression, assessed by the investigator per RECIST v1.1. OS is defined as the time from treatment start to death due to any cause or until the end of the previously determined follow-up period, which in this study is of 78 weeks. TTF is defined as the time from treatment start to the time at which the patient discontinues treatment due to any cause, including disease progression assessed by the investigator as per RECIST v1.1, toxicity, death or at the patient’s request. DOR is defined as the time from start of the treatment response to disease progression or death in those patients who show an objective response as per RECIST 1.1 criteria. DCR is defined as the sum of complete responses (CR) + partial responses (PR) + stable disease (SD). TS is defined as the percentage of tumor shrinkage with respect to the baseline measurements as per RECIST v1.1. Secondary endpoints Molecular aspects Correlation ratio of mutational status and documented clinical response. A progress curve showing the EGFR mutational status (including the T790M mutation) in plasma and serum longitudinally. Percentage levels of BIM mRNA as well as mRNA levels of other biomarkers related to EGFR TKI response. Percentage of patients with mutations at the site of covalent binding to the drug (C797) or other mutations in tissue and correlation ratio of documented clinical response;Timepoint(s) | — |
Countries
Spain
Contacts
Public ContactProject Manager
Medica Scientia Innovation Research (MedSIR ARO)
Outcome results
None listed