PRe-Operative Gefitinib in Resectable EGFR Mutation Positive Lung Cancer With Sector Sequencing for Biomarker Discovery (PROGRESS)

PROGRESS: PRe-Operative Gefitinib in Resectable EGFR Mutation Positive Lung Cancer With Sector Sequencing for Biomarker Discovery

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.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Gefitinib

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 169610
    • National Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Gefitinib; Gefitinib 250mg oral daily will be given for 4 weeks prior to surgery	Drug: Gefitinib; 250mg oral daily for 4 weeks; Other Names: Iressa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EGFR TKI sensitivity biomarkers determination	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	4 to 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rates after 4 weeks of neoadjuvant gefitinib	To determine response rates after 4 weeks of neoadjuvant gefitinib as evaluated by RECIST 1.1	4 to 6 weeks

Other Outcome Measures

Outcome Measure	Time Frame
Clonal heterogeneity using whole exome and RNA-sequencing of tumour sectors as well as resected lymph nodes	4 to 6 weeks
Clonal heterogeneity recapitulation through CTC, plasma DNA and functional imaging	4 to 6 weeks

Collaborators and Investigators

• Sponsor: National Cancer Centre, Singapore

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 27, 2015
• Primary Completion (ACTUAL): February 21, 2018
• Study Completion (ACTUAL): February 21, 2018

Study Registration Dates

• First Submitted: June 14, 2016
• First Submitted That Met QC Criteria: June 14, 2016
• First Posted (ESTIMATE): June 17, 2016

Study Record Updates

• Last Update Posted (ACTUAL): June 2, 2021
• Last Update Submitted That Met QC Criteria: May 31, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Gefitinib
• Other Study ID Numbers: ECRU-LUNG-2013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO