Combination of Gefitinib With Chemotherapy or Anti-angiogenesis as 1st Line Treatment in Advanced NSCLC Patients Detected With Bim Deletion or Low EGFR Activating Mutation Abundance
Overview
- Phase
- Phase 2
- Intervention
- Gefitinib
- Conditions
- Non-small-cell Lung Cancer
- Sponsor
- Caicun Zhou
- Enrollment
- 180
- Locations
- 1
- Primary Endpoint
- Progression free survival
- Last Updated
- 9 years ago
Overview
Brief Summary
This is a single arm phase II clinical trial, which aims to evaluate the effectiveness of combination of gefitinib and doublet chemotherapy or antiangiogenesis in advanced non-small cell lung cancer patients with EGFR activating mutation, accompanied with Bim deletion or low activating EGFR mutation abundance.
Detailed Description
BIM deletion polymorphism and low EGFR mutation abundance were poor clinical response markers to EGFR-TKIs in NSCLC patients who had EGFR mutations.This is a phase II clinical trial to investigate the efficacy of combination treatment for patients harboring risk factors. Advanced EGFR mutated NSCLC Patients with Bim deletion or EGFR low mutation abundance were randomizely divided into three treatment groups: A:Gefitinib 250mg Qd B:Gefitinib 250mg Qd combined with doublet chemotherapy: Pemetrexed (500mg/m²day 1 intravenously) plus carboplatin (AUC=5,day 1,intravenously) every 21 days, Gemcitabine (1000 mg/m² days 1, day8, intravenously) plus carboplatin (AUC=5,day 1,intravenously) every 21 days C:Gefitinib 250mg Qd combined with bevacizumab 7.5mg/kg intravenously per 21 days.
Investigators
Caicun Zhou
Professor, doctor
Tongji University
Eligibility Criteria
Inclusion Criteria
- •Histologically documented, locally advanced or recurrent (stage IIIb and not amenable to combined modality treatment) or metastatic (stage IV) non-small cell lung cancer, anti-cancer treatment naiive
- •EGFR exon 19 deletion or exon 21 L858R.
- •Bim deletion by realtime PCR, or low abundance for EGFR mutation, for 19Del less than 4.9%, for L858R less than 9.5%.
- •ECOG performance status of ≤
- •Patients must have measurable disease according to the RECIST (version 1.1) criteria.
- •Life expectancy of at least 12 weeks
- •Written (signed) informed Consent to participate in the study.
- •Adequate organ function as defined by the following criteria:
- •Liver function: SGOT (AST) and SGPT (ALT) ≤ 2.5 X ULN in the absence of liver metastases or up to 5 X ULN in case of liver metastases. Total bilirubin ≤ 1.5ULN.
- •Bone marrow function: Granulocyte count ≥ 1,500/mm3 and platelet count ≥100,000/mm3 and hemoglobin ≥90g/dl.
Exclusion Criteria
- •Patients with prior chemotherapy or systemic anti-cancer therapy including target therapy targeting HER family members (such as erlotinib, gefitinib, cetuximab, trastuzumab, etc). Previous adjuvant or neo-adjuvant treatment for non-metastatic disease is permitted if completed ≥ 6 months before the enrollments.
- •Patients with history of any other malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer).
- •Patients who have brain metastasis or spinal cord compression. It is permitted if the patient has been treated with surgery and/or radiation with evidence of stable disease for at least 4 weeks.
- •Patients who are at risk (in the investigator's opinion) of transmitting human immunodeficiency virus (HIV) through blood or other body fluids.
- •lactating women
- •Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study.
- •Unwilling to write informed consent to participate in the study or unwilling to receive follow-up
- •Tumor invade big vessels or close to big vessels (less than 5mm)
- •Obvious cavity or necrosis formed in the tumor, Uncontrolled hypertension, Myocardial ischemia or infarction more than stage II, cardiac insufficiency. Abnormal coagulation (INR\>1.5 or PT\>ULN+4, or APTT\>1.5 ULN), bleeding tendency or receiving coagulation therapy
- •Hemoptysis, more than 2.5ml daily
Arms & Interventions
Gefitinib single agent
Advanced NSCLC patients with EGFR activating mutation (L858R, 19Del) received Gefitinib 250mg Qd orally until progression, intolerable toxicity or death.
Intervention: Gefitinib
Gefitinib combined with chemotherapy
Gefitinib 250mg Qd combined with pemetrexed or gemcitabine plus carboplatin: Pemetrexed (500mg/m²day 1 intravenously) plus carboplatin (AUC=5,day 1,intravenously) every 21 days, Gemcitabine (1000 mg/m² days 1,d8, intravenously) plus carboplatin (AUC=5,day 1,intravenously) every 21 days
Intervention: Gefitinib
Gefitinib combined with chemotherapy
Gefitinib 250mg Qd combined with pemetrexed or gemcitabine plus carboplatin: Pemetrexed (500mg/m²day 1 intravenously) plus carboplatin (AUC=5,day 1,intravenously) every 21 days, Gemcitabine (1000 mg/m² days 1,d8, intravenously) plus carboplatin (AUC=5,day 1,intravenously) every 21 days
Intervention: pemetrexed or gemcitabine plus carboplatin,
Gefitinib combined with antiangiogenesis
Gefetinib 250mg Qd combined with bevacizumab 7.5mg/kg per 21 days
Intervention: Gefitinib
Gefitinib combined with antiangiogenesis
Gefetinib 250mg Qd combined with bevacizumab 7.5mg/kg per 21 days
Intervention: bevacizumab
Outcomes
Primary Outcomes
Progression free survival
Time Frame: 8 weeks
From start of anti-cancer therapy untill progression or death
Secondary Outcomes
- overall survival(36 months)
- side effect(8 weeks)
- quality of life(24 months)