The purpose of this study is to evaluate the safety and clinical activity of Apatinib in combination with AP(Pemetrexed/Carboplatin) or AC(Pemetrexed/Carboplatin) as first-line chemotherapy in subjects with advanced EGFR wild type non-squamous non-small cell lung cancer(NSCLC).
Apatinib, an oral highly potent tyrosine-kinase inhibitor targeting VEGFR-2, has demonstrated improved survival in previously treated patients with advanced non-small-cell lung cancer(NSCLC). The phase I study is conducted to explore the safety, tolerability, dose-limiting toxicities(DLT), Maximum Tolerable Dose(MTD), and preliminary anti-tumor activity of Apatinib combined with platinum-based doublet chemotherapy(PB-DC) in first-line advanced EGFR wild type non-squamous non-small cell lung cancer. This will use a dose reduction trial design. A cohort of 3\~6 subjects will be enrolled at each dose level, If 0 of 3 or ≤ 1 of 6 subjects experience a DLT, the phase I trial will stop and the current dose will be considered the MTD. If 1 of 6 or more subjects experiences a DLT, dose reduce to the next dose will occur. Following completion of the dose de-escalation trial and determination of MTD, A randomized controlled trial(RCT) including 30 subjects may be enrolled to further evaluate safety, tolerability, and preliminary anti-tumor activity of Apatinib in combination with platinum-based doublet chemotherapy(PB-DC) in the same target population.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
48
Doses to be determined following the completion of Phase I of the study.
Pemetrexed(A) 500mg/m2, IV, Day 1; Cisplatin(P) 25mg/m2,IV,Day 1-3 or Carboplatin(C) area under curve(AUC)=5, IV, Day 1; AP or AC will be administered every 21 days starting on Day 1.
250mg/d,q.d.,p.o.every 21 days.
West China Hospital, Sichuan University
Chengdu, Sichuan, China
RECRUITINGObjective response rate(ORR)
To determine ORR of Apatinib in combination with AP or AC in subjects with advanced EGFR wild type non-squamous non-small cell lung cancer. ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1
Time frame: Up to 36 months
Progression-free survival (PFS)
PFS defined as the time from first dose of study treatment until the first date of either objective disease progression or death due to any cause.
Time frame: Up to 36 months
Disease Control Rate (DCR)
Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.
Time frame: Up to 36 months
median Overall Survival
median Overall survival is defined as the time in months from the start of protocol treatment until the date of death, or the date of last follow-up if alive. Kaplan-Meier methods will be used to estimate overall survival.
Time frame: Up to 36 months
One-year Overall Survival Rate
Kaplan Meier methods were used to estimate the 1-year survival probabilities for time to death from any cause. Estimates of the 1-year (365 day) survival probabilities and corresponding 95% confidence intervals (CI) were presented by treatment group.
Time frame: Up to 36 months
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500mg/d,q.d.,p.o.every 21 days.
750mg/d,q.d.,p.o.every 21 days.