PROGRESS: PRe-Operative Gefitinib in Resectable EGFR Mutation Positive Lung Cancer With Sector Sequencing for Biomarker Discovery
Overview
- Phase
- Phase 2
- Intervention
- Gefitinib
- Conditions
- Non-small Cell Lung Cancer
- Sponsor
- National Cancer Centre, Singapore
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- EGFR TKI sensitivity biomarkers determination
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This is a pharmacodynamic study to evaluate the effect of gefitinib as induction therapy for patients who have resectable, Epidermal growth factor receptor (EGFR) sensitizing mutation lung cancer.
Detailed Description
Selected patients will receive 4 weeks of gefitinib before surgery. A Positron Emission Tomography - Computed Tomography (PET- CT) will be performed before and after gefitinib to assess the response. Circulating tumour cells (CTCs) and plasma Deoxyribonucleic acid (DNA) will be acquired at baseline, 2 weeks and 4 weeks after gefitinib treatment. Resected tumor will be sectored in details to study the spatial heterogeneity.
Investigators
Eligibility Criteria
Inclusion Criteria
- •EGFR mutation positive Non-Small Cell lung cancer (NSCLC) (regardless of smoking status), or control group may encompass other molecular subtypes of lung cancer e.g. anaplastic lymphoma kinase (ALK) and Kirsten rat sarcoma viral oncogene homolog (KRAS).
- •All early stage patients with NSCLC who are deemed surgically resectable.
- •All patients must have histologically proven NSCLC, with known EGFR mutation
- •Patients should be fit for either lobectomy/ pneumonectomy with or without lymph node sampling.
- •Primary tumour should be at least 2 cm in size (Tumor stage 1b).
- •Willing to provide informed consent.
Exclusion Criteria
- •Known severe hypersensitivity to gefitinib or any of the excipients of this product
- •Any serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study.
- •Interstitial lung disease (ILD) or pulmonary fibrosis; impaired pulmonary function (e.g. FEV1 \<40% predicted value, artery blood gas PaO2\<60mmHg)
- •Patients with prior exposure to agents directed at the Human epidermal receptor (HER) axis (e.g. erlotinib, gefitinib, cetuximab, trastuzumab).
- •Patients with prior exposure to chemotherapy, irradiation or systemic anti-cancer therapy (e.g. monoclonal antibody therapy) for lung cancer.
- •Any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within six months, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease).
- •Evidence of any other disease, neurological or metabolic dysfunction, physical examination or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the subject at high risk for treatment-related complications.
- •Patient who has serious active infection.
- •Patients who harbouring exon 20 T(Threonine)790M (Methionine) mutation.
- •Pregnancy or breast feeding.
Arms & Interventions
Gefitinib
Gefitinib 250mg oral daily will be given for 4 weeks prior to surgery
Intervention: Gefitinib
Outcomes
Primary Outcomes
EGFR TKI sensitivity biomarkers determination
Time Frame: 4 to 6 weeks
Determine EGFR tyrosine kinase inhibitor (TKI) sensitivity biomarkers in responders vs non responders, as categorized by either Response Evaluation Criteria In Solid Tumors (RECIST) stable disease (SD) vs Partial response (PR) or median percentage tumour shrinkage
Secondary Outcomes
- Response rates after 4 weeks of neoadjuvant gefitinib(4 to 6 weeks)