A Randomized, Placebo-controlled, Double-blind, Multicenter, Phase II Study of Apatinib as Third Line Treatment in Patients With Advanced Non-squamous and Non-small Cell Lung Cancer
- ≥ 18 and ≤ 70 years of age
- Histologically or cytologic confirmed advanced non-squamous and non-small cell lung
- At least one measurable lesion which has not received radiotherapy (larger than 10 mm
in diameter by spiral CT scan)
- Have failed for 2 lines of chemotherapy including EGFR-TKI.
- ECOG performance scale 0 - 1.
- Life expectancy of more than 3 months.
- Duration from the last therapy is more than 6 weeks for nitroso or mitomycin
- More than 4 weeks after operation or radiotherapy
- More than 4 weeks for cytotoxic agents or tyrosine kinase inhibitors inhibitors
- Adequate hepatic, renal, heart, and hematologic functions (hemoglobin ≥ 90g/L,
platelets ≥ 80×10^9/L, neutrophils ≥ 1.5×10^9/L, total bilirubin within 1.25×the
upper limit of normal(ULN), and serum transaminase≤2.5×the ULN (If liver metastases,
serum transaminase≤5×the ULN), serum creatine ≤ 1.5 x ULN, creatinine clearance rate
- signed and dated informed consent.Willingness and ability to comply with scheduled
visits, treatment plans, laboratory tests, and other study procedure.
- Squamous cell carcinoma (including adenosquamous carcinoma, undifferentiated
carcinoma); small cell lung cancer (including small cell and non-small cell mixed
- Pregnant or breastfeeding women
- Intercurrence with one of the following: hypertension, coronary artery disease,
arrhythmia and heart failure
- Any factors that influence the usage of oral administration
- PT, APTT, TT, Fbg abnormal, Receiving the therapy of thrombolysis or anticoagulation.
- Within 4 weeks before the first use of drugs, occurs pulmonary hemorrhage (≥ CTCAE
class 2) or other parts' hemorrhage (≥ CTCAE class 3).
- Long-term untreated wounds or fractures.
- Within 6 months before the first treatment occurs artery / venous thromboembolic
events, such as cerebral vascular accident (including transient ischemic attack),
deep vein thrombosis and pulmonary embolism, etc.
- Application of anticoagulants or vitamin K antagonists such as warfarin, heparin or
its analogues; If the prothrombin time international normalized ratio (INR) ≤ 1.5,
with the purpose of prevention, the use of small doses of warfarin (1mg orally, once
daily) or low-dose aspirin (between 80mg to 100mg daily) is allowed.
- Abuse of alcohol or drugs
- Less than 4 weeks from the last clinical trial
- Treatment with VEGFR, PDGFR, sSRC-TKI before.
- History of any second malignancies within 3 years except cured basal cell carcinoma
of skin and carcinoma in-situ of uterine cervix.