The Continuation of Gefitinib Treatment Beyond Progression in Non-small Cell Lung Cancer Patients With EGFR Mutation

NCT03399669 | Unknown Phase 2

• 1 other identifier: 2014-11-095
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Although EGFR-TKIs such as gefitinib, erlotinib or afatinib are recommended as first-line therapy in patients with advanced, recurrent or metastatic nonsquamous NSCLC patients who have known active EGFR mutation and achieved response to EGFR TKIs experience disease progression eventually with 10-14 moths of median progression free survival.6 Platinum-doublets combination chemotherapy remains standard of care for patients with progressive disease. However, patients may derive benefit from EGFR TKIs after RECIST-assessed progression especially for those who experience slow progression. And previous report suggested that premature discontinuation of EGFR TKIs has resulted in rapid progression in symptoms and tumor growth.7 Recently, a prospective phase II single arm study in Asian patients with EGFR mutation-positive NSCLC to determine the continuation of erlotinib beyond progression judged by investigators showed that additional PFS of 3.1 months can be achieved with continuation of erlotinib without serious additional toxicities.8 Until now, no prospective study has been conducted for gefitinib. In this study the continuation of gefitinib beyond RECIST progression will be investigated to determine the clinical outcomes including the duration of treatment and safety. This is a single-arm phase II trial to evaluate the efficacy and safety of continuation of gefitinib in EGFR mutant NSCLC patients who experience RECIST progression. Based on the results of "ASPIRATION" study, the median PFS for continuation of gefitinib will be around 3 months. The study treatment will be of no interest if the true median PFS is 2.5 months or shorter. In contrast, it will be of interest if the true median PFS is 3.5 months or longer. Considering 1 sided alpha of 0.05 and 90% of power, 95 patients are required. A total of 100 patients will be needed considering 5% of drop-out rate. 6 months of accrual and additional 6 months of follow-up will be assumed for this study. Patients will be treated 250 mg/day of gefitinib orally (1 cycle for 28 days). Cycles were repeated until disease progression, unacceptable toxicity, or until the patient or the investigator requested therapy discontinuation.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Time from RECIST progression to secondary disease progression

  3 months

Study Arms (1)

gefitinib

EXPERIMENTAL

Patients will be treated 250 mg/day of gefitinib orally (1 cycle for 28 days). Cycles were repeated until disease progression, unacceptable toxicity, or until the patient or the investigator requested therapy discontinuation.

Drug: gefitinib

Interventions

gefitinib DRUG

Patients will be treated 250 mg/day of gefitinib orally (1 cycle for 28 days). Cycles were repeated until disease progression, unacceptable toxicity, or until the patient or the investigator requested therapy discontinuation.

gefitinib

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed stage IIIB/IV or recurrent NSCLC with activating EGFR mutation in exon 18 through exon 21 except T790M
• Patients who achieved complete/partial response more than 4 months or stable disease more than 6 months with first-line or second line gefitinib
• Patients who experience disease progression by RECIST 1.1 criteria
• Age ≥ 18years
• ECOG performance status of 0 to 2
• Adequate organ function as evidenced by the following; Absolute neutrophil count \> 1.5 x 109/L; platelets \> 100 x 109/L; total bilirubin ≤1.5 UNL; AST and/or ALT \< 5 UNL, CCr ≥ 50mL/min
• Baseline adverse event of gefitinib ≤ Grade 2
• Written informed consent form

You may not qualify if:

• Prior treatment with EGFR TKI
• Patients who required dose reduction of gefitinib
• Surgery undertaken less than 4 weeks before the study
• Localized radiotherapy unless completed more than 2 weeks before the study
• Uncontrolled systemic illness such as DM, CHF, unstable angina, hypertension or arrhythmia
• Pregnant or nursing women ( Women of reproductive potential have to agree to use an effective contraceptive method (hormonal or barrier methods))
• Uncontrolled symptomatic brain metastasis
• Prior history of malignancy within 5 years from study entry except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer, well-treated thyroid cancer
• Concomitant use of CYP3A4 inducers/inhibitors
• Prolonged QT interval in ECG (QTc \>450 msec)
• Patients who cannot take a medicine orally or who have a gastrointestinal absorption disorder

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine

Seoul, 135-710, South Korea

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Gefitinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Myung-Ju Ahn

  Samsung Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD,PhD,Professor

Study Record Dates

• First Submitted: January 9, 2018
• First Posted: January 16, 2018
• Study Start: February 17, 2015
• Primary Completion: June 30, 2018
• Study Completion: December 31, 2018
• Last Updated: January 16, 2018

Record last verified: 2018-01

Locations

KR (1)