Osimertinib for Advanced EGFR-positive NSCLC Patients
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age21-99
SponsorNational University Hospital, Singapore
About this trial
Lung cancer is the leading cause of cancer incidence (11.6%) and mortality (18.4%) globally\[1\]. Development of targeted therapies in the context of precision medicine changed the way lung cancer was diagnosed and treated. Small molecule inhibitors, like tyrosine kinase inhibitors (TKIs), are now standard first-line therapy for EGFR-positive non-small cell lung cancer (NSCLC). First-generation EGFR-TKIs gefitinib and erlotinib bind competitively to the ATP-binding site of EGFR TK domain. This binding in second-generation TKI afatinib is irreversible. These drugs have improved better outcome compared to standard conventional chemotherapy In spite of this, more than half of the patients with an EGFR TKI treatment develop resistance. Deletion in exon 19 and single point substitution L858R in exon 21 accounting for 44% and 41% of all EGFR mutations, respectively are the most common mutations in EGFR gene which cause this resistance in the patients. Asia has the highest prevalence of EGFR mutations (38.4%), followed by America (24.4%) and Europe (14.1%). Median progression-free survival of EGFR mutated NSCLC patients under erlotinib or gefitinib has been around 12 months and 5-year survival was 15%
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Provision of informed consent prior to any study-specific procedure
Patients must be ≥ 18 years old
Locally advanced /metastatic NSCLC not responsive to surgery or radiotherapy
Validated activating EGFR sensitising mutations with or without T790M resistance mutation at the time of recruitment for patients who have no prior EGFR TKI treatment.
Disqualifiers
Treatment with other EGFR-TKI within 8 days or within five half-lives of the compound before study entry whichever is the longer; any cytotoxic chemotherapy, or other anticancer drugs against NSCLC within 14 days of study entry
Previously treated with an immune checkpoint inhibitor
Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years
Radiotherapy to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks before the study entry
Trial population
Osimertinib for Advanced EGFR-positive NSCLC Patients
Trial design
Design model
Case-control
Time perspective
Prospective
Treatments tested in this trial
Not listed
Trial groups
No trial groups listed
Trial outcomes
Primary outcomes
1
To investigate the safety of Osimertinib 80mg/eod using TCAE v4.0
To investigate the safety of Osimertinib 80mg/eod using TCAE v4.0 To investigate the safety of Osimertinib 80mg/eod. Parameters like PFS, DoR, the incidence of brain metastases and OS will be assessed for the efficacy using RECIST criteria version 1.1. PFS in the brain will be another endpoint. Adverse events will be graded according to CTCAE v4.0 by recording vital signs, physical examinations, weight, ECG, ECOG performance status, clinical chemistry, haematology, urinalysis. We would use ctDNA to detect the mutations and compare the progress of the disease or the outcome of patients besides clinical assessments. The relationship between PK and selected efficacy, pharmacodynamic markers (like duration of inhibition of EGFR by hair follicle sampling) and safety endpoints will be assessed as well.
Time frame
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Source ClinicalTrials.gov