Osimertinib for Advanced EGFR-positive NSCLC Patients

NCT05037331 | Recruiting

• 1 other identifier: 2020/00190
• Study Type: observational
• Target: 58
• Locations: 1 country
• Sites: 1

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%

Conditions

EGFR Positive Non-small Cell Lung Cancer; Non Small Cell Lung Cancer

Keywords

Osimertinib; advanced EGFR-positive; NSCLC; orally administered

Outcome Measures

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.

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Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Osimertinib for Advanced EGFR-positive NSCLC Patients

You may qualify if:

• 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.
• Patients must be EGFR treatment naïve.
• ECOG Performance status is 0-1 with no deterioration over the last 2 weeks prior to study recruitment.
• 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)

You may not qualify if:

• 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
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of study treatment with the exception of alopecia grade 2 and platinum-related neuropathy.
• Unstable spinal cord compression/brain metastases unless asymptomatic and not requiring steroids for at least 2 weeks prior to the start of study treatment. For patients with brain metastases, gamma knife or stereotactic brain surgery is allowed prior to study treatment.
• Major surgery within 4 weeks of starting study treatment and patients must have recovered from any effects of any major surgery. Minor surgery is allowed.
• Patients currently receiving or unable to stop use medications or herbal supplements that are potent inhibitors of CYP3A4 (at least 1 week prior) and potent inducers of CYP3A4 (at least 3 weeks prior). All patients must avoid concomitant use of any medications, herbal supplements and/or foods with known inducer/inhibitory effects on CYP3A4 unless part of protocol treatment.
• Severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which based on investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or having active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
• Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTc using Fredericia's formula) \> 470 msec
• 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)
• Any factors increasing the risk of QTc prolongation or arrhythmias 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
• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the drug or previous significant bowel resection that would preclude adequate absorption of Osimertinib

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital

Singapore, Singapore

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Goh

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Goh Boon Cher

CONTACT

67725555; phcgbc@nus.edu.sg

goh

CONTACT

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2021
• First Posted: September 8, 2021
• Study Start: July 22, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: September 25, 2025

Record last verified: 2025-09

Locations

SG (1)