This is an open-label, multicenter, randomized, phase II clinical trial, which aims to evaluate the effectiveness and safety of gefitinib versus combination of gefitinib and doublet chemotherapy or apatinib in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) activating mutation (exon 19 deletion or exon 21 L858R point mutation), accompanied with Bim deletion or low activating EGFR mutation abundance.
BIM (bcl-2 interacting mediator of cell death) deletion polymorphism and low EGFR mutation abundance were poor clinical response markers to epidermal growth factor receptor tyrosine kinase inhibitors (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 above risk factors. Advanced EGFR mutated NSCLC Patients with Bim deletion or EGFR low mutation abundance were randomized divided into following three treatment groups: A: gefitinib 250mg Qd combined with doublet chemotherapy: pemetrexed (500mg/m²,day 1 ,intravenously) plus carboplatin (AUC=5,day 1,intravenously) every 21 days. B: gefitinib 250mg Qd combined with apatinib 250mg/d intravenously per 21 days. C: gefitinib 250mg Qd
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
100
Gefitinib 250mg, p.o., q.d., continuous regimens on an empty stomach or after meal for 2 hours until disease progression, intolerable toxicity or patient withdraw ICF. Pemetrexed (500mg/m²day 1 intravenously) plus carboplatin (AUC=5,day 1,intravenously) every 21 days. Every 3 weeks is a chemotherapy cycle, and 4 chemotherapy cycles is maximum limit.
gefitinib 250mg, p.o., q.d., continuous regimens on an empty stomach or after meal for 2 hours. Apatinib 250mg, p.o., q.d. per 21 days. until disease progression, intolerable toxicity, patient withdraw ICF or death.
Patients received Gefitinib 250mg q.d. orally until disease progression, intolerable toxicity or death.
Shanghai Pulmonary Hospital;
Shanghai, Shanghai Municipality, China
RECRUITINGProgression free survival
From start of anti-cancer therapy until progression or death
Time frame: 8 weeks
overall survival
evaluated in the 36th since treatment begain
Time frame: 36 months
objective response rate
Evaluated the rate of complete response and partial response in the 8 weeks since treatment began
Time frame: 8 weeks
disease control rate
Evaluated the rate of complete response,partial response and stable disease in the 8 weeks since anti-cancer therapy
Time frame: 8 weeks
duration of response
interval between the time which complete response or partial response happened and progressive disease or death
Time frame: 8 weeks
safety evaluation
Safety observation indexes were listed as following: adverse events and serious adverse events (according to CommonTerminology Criteria Adverse Events Version 4.03), physical exam, vital signs(blood pressure, heart rate, respiratory rate,body temperature), weight variation, laboratory examination(hematology, blood biochemistry, urinalysis and so on), electrocardiograph(ECG),ultrasonic cardiogram(UCG), ect.
Time frame: 8 weeks
compare quality of life
Quality of Life Questionnaire(including QLQ-C30 and QLQ-LC13) evaluated since treatment began.At the end of the trial, the differences between the two indicators were compared with Mixed-effects model repeated measures (MMRM), where the baseline was scored as a covariant and the treatment group as a fixed variable. In addition, the baseline values of the two scores, the value of each visit, and the change value of the baseline were statistically described.
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Time frame: 24 months