Third-line Treatment of Gefitinib in NSCLC Patients

Third-line Treatment of Gefitinib in NSCLC Patients Who Had Received First-line Gefitinib With EGFR 19del/L858R Mutation and Tumor Progression After the Second-line Chemotherapy: a Single-arm, Prospective and Multi-center Study

The purpose of this study is to evaluate the disease control rate (DCR) of gefitinib as third-line retreatment in stage IIIB/IV NSCLC with EGFR 19del/L858R positive mutation patients who had benefited from first-line gefitinib treatment with EGFR 19del/L858R positive mutation and tumor progression after the second-line chemotherapy

Study Overview

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

Detailed Description

• Primary Study Objective: To evaluate the disease control rate (DCR) of gefitinib as third-line retreatment in stage IIIB/IV NSCLC with EGFR 19del/L858R positive mutation patients who had benefited from first-line gefitinib treatment with EGFR 19del/L858R positive mutation and tumor progression after the second-line chemotherapy
• Secondary Study Objectives: To evaluate objective response rate (ORR), progressive-free survival (PFS), overall survival(OS) and quality of life (QoL) of gefitinib as third-line retreatment in NSCLC patients To evaluate the safety of gefitinib as third-line treatment in NSCLC patients
• Exploratory analyses: To dynamically monitor EGFR mutation status and explore the relationship with clinical outcome

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210002
      • Nanjing General Hospital of Nanjing Military Command

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The subject or legal guardian could understand and sign informed consent form.
2. Male or female aged 18 years or older;
3. Subjects were diagnosed with stage IIIB or IV NSCLC before starting the first dose of gefitinib third-line treatment;
4. EGFR exon 19 deletion or exon 21 L858R substitution mutation confirmed;
5. ECOG performance status 0-2;
6. Life expectancy of at least 12 weeks or longer;
7. Has at least one measureable lesion by RECIST 1.1;
8. NSCLC of enrolled subjects previously progressed after first-line gefitinib treatment (PFS ≥ 6 months) and progressed again after second-line chemotherapy (not limited for chemotherapy regimen, ≥ 4 cycles of chemotherapy). Investigator considers adopting third-line gefitinib retreatment;

9. Criteria for laboratory examinations:

   • Total bilirubin (TB) ≤ 1.5 times upper limit of normal
   • Aspartate aminotransferase(AST), alanine aminotransferase (ALT) ≤2 times upper limit of normal; for subjects with hepatic metastasis, AST,ALT≤ 5 times upper limit of normal
   • Creatinine clearance≥45ml/min

Exclusion Criteria:

1. Known severe hypersensitivity to gefitinib or any ingredients of the product;
2. Patients with prior exposure to agents directed at the EGFR axis except gefitinib (e.g. erlotinib, cetuximab, trastuzumab) ;
3. Pre-existing interstitial lung disease or pulmonary fibrosis evidenced by CT scan at baseline;
4. Neutrophil count <1.0×109/L or platelet count <50×109/L;
5. Severe infection, uncontrolled systemic disease (e.g cardiopulmonary insufficiency, fatal arrhythmias, hepatitis, etc);
6. Pregnancy or breast-feeding;
7. Women of childbearing age refuse to take adequate contraception measures during gefitinib treatment
8. Subjects with other malignant tumors combined;
9. Known or suspected brain metastases or spinal cord compression, unless treated with surgery and/or radiation and stable without steroid treatment for at least 4 weeks prior to the first dose of study medication;
10. Subjects are unable to take medications orally or have digestive malabsorption;
11. Investigators consider subjects should not be involved in the study.

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 250mg/d; Subjects will receive the oral administration of gefitinib 250mg/d until the tumor progression, perform scheduled visits in investigational sites at interview day and complete related examinations during follow-up period.	Drug: Gefitinib; Subjects will receive the oral administration of gefitinib 250mg/d until the tumor progression.; Other Names: Iressa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease Control Rate (DCR)	week 8

Secondary Outcome Measures

Outcome Measure	Time Frame
objective response rate (ORR), progressive-free survival (PFS), overall survival(OS)	until the death of last subject or 2 years after enrollment

Collaborators and Investigators

• Sponsor: Guangdong Association of Clinical Trials
• Investigators: Principal Investigator: Yong Song, Ph.D, Nanjing PLA General Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 7, 2014
• Primary Completion (ACTUAL): April 10, 2017
• Study Completion (ACTUAL): April 10, 2018

Study Registration Dates

• First Submitted: August 28, 2013
• First Submitted That Met QC Criteria: August 28, 2013
• First Posted (ESTIMATE): September 2, 2013

Study Record Updates

• Last Update Posted (ACTUAL): February 6, 2020
• Last Update Submitted That Met QC Criteria: February 5, 2020
• Last Verified: April 1, 2018

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; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Gefitinib
• Other Study ID Numbers: CTONG1304

Plan for Individual participant data (IPD)

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