EGFR Positive Non-small Cell Lung Cancer, Non Small Cell Lung Cancer
Conditions
Keywords
Osimertinib, advanced EGFR-positive, NSCLC, orally administered
Brief summary
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%
Detailed description
To evaluate the efficacy (Objective Response Rate), safety and tolerability of 80mg Osimertinib eod dosing in NSCLC patients with sensitizing EGFR mutations and/or EGFR T790M resistance mutation that have no prior EGFR treatment. To investigate the efficacy and 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.
Interventions
None listed
Sponsors
National University Hospital, Singapore
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
21 Years to 99 Years
Inclusion criteria
* For inclusion in the study subjects should fulfil the following criteria: 1. Provision of informed consent prior to any study-specific procedure 2. Patients must be ≥ 18 years old 3. Locally advanced /metastatic NSCLC not responsive to surgery or radiotherapy 4. 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. 5. Patients must be EGFR treatment naïve. 6. ECOG Performance status is 0-1 with no deterioration over the last 2 weeks prior to study recruitment. 7. Normal organ and bone marrow function measured within 28 days before the study as defined below: * Haemoglobin ≥ 9.0 g/dL and no blood transfusions in the 28 days prior to entry * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L * No features suggestive of MDS/AML on peripheral blood smear * White blood cells (WBC) \> 3x109/L * Platelet count ≥ 100 x 109/L * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) * AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be ≤ 5x ULN * Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN) * ECOG performance status 0-2 8. A life expectancy ≥ 12 weeks in all patients. 9. Females in childbearing age should be using adequate contraceptive measures, should not be breastfeeding and their pregnancy test prior to the start of treatment must be negative. Evidence of non-child-bearing potential is fulfilled by one of the following criteria at screening: * The post-menopausal period defined as age ≥50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments * Women \<50 years old they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range. * Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not a tubal ligation 10. Male patients should be willing to use barrier contraception 11. The patient is willing to comply with the protocol during the study including undergoing treatment and scheduled visits and examinations including follow up. 12. At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and is considered suitable for accurate repeated measurements.
Exclusion criteria
* Patients should not enter the study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To investigate the safety of Osimertinib 80mg/eod using TCAE v4.0 | 4 | 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. |
Countries
Singapore
Contacts
Primary ContactGoh Boon Cher
Backup Contactgoh
Outcome results
None listed