Clinical trial NCT02804776: PRe-Operative Gefitinib in Resectable EGFR Mutation Positive Lung Cancer With Sector Sequencing for Biomarker Discovery
Official title: PROGRESS: PRe-Operative Gefitinib in Resectable EGFR Mutation Positive Lung Cancer With Sector Sequencing for Biomarker Discovery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Lead sponsor: National Cancer Centre, Singapore
Sponsor class: OTHER
First posted: 2016-06-17
Enrollment: 15
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: EGFR TKI sensitivity biomarkers determination
timeFrame: 4 to 6 weeks
Secondary outcomes:
measure: Response rates after 4 weeks of neoadjuvant gefitinib
timeFrame: 4 to 6 weeks
Other outcomes:
measure: Clonal heterogeneity using whole exome and RNA-sequencing of tumour sectors as well as resected lymph nodes
timeFrame: 4 to 6 weeks
measure: Clonal heterogeneity recapitulation through CTC, plasma DNA and functional imaging
timeFrame: 4 to 6 weeks
Locations:
city: Singapore
country: Singapore
facility: National Cancer Centre
Study officials:
affiliation: National Cancer Centre, Singapore
name: Daniel SW Tan
role: PRINCIPAL_INVESTIGATOR
References: