| Eligibility |
Inclusion Criteria:
- 18 Years to 75 Years patients voluntarily participate in this study, signed and dated
informed consent with good compliance and follow-up;
- Diagnosed as locally advanced and / or metastatic non-squamous non-small cell lung
adenocarcinoma (NSCLC) by cytology or histology; Provide detectable specimens (tissue
or blood) for genotyping before enrollment, and the patients should be with negative
EGFR, ALK and ROS1 gene test results, and without prior systemic therapy;
- At least one target lesion that has not received radiotherapy, and has accurate
measurement by magnetic resonance imaging (MRI) or computed tomography (CT)
(conventional CT=20 mm or spiral CT=10 mm) in at least 1 direction;
- Life expectancy is at least 3 months;
- ECOG PS Scoring: 0~1 point;
- The main organs function are normally, the following criteria are met:
- Blood routine examination criteria (no blood transfusion and blood products
within 14 days, no correction by G-CSF and other hematopoietic stimuli):
i) hemoglobin (HB) =90g/L ii) neutrophil absolute (ANC) =1.5×109/L iii) platelet
(PLT) =80×109/L
- Biochemical tests meet the following criteria i) total bilirubin (TBIL) =1.5
times of upper limit of normal (ULN); ii) alanine aminotransferase (ALT) and
aspartate aminotransferase (AST)=2.5 ULN, if liver metastasis occurred, ALT and
AST =5 ULN; iii) serum creatinine (Cr) =1.25 ULN or creatinine clearance
(CCr)=45mL/min (Cockcroft-Gault formula).
- Female patients of childbearing age agree that contraceptive measures must be used
within the study period and within 8 weeks after the end of the study drug treatment.
The serum or urine test indicates unpregnancy within 7 days prior to the study. Male
patients agree to have contraceptive use during the study period and within 8 weeks
after the end of the study period or have had surgical sterilization.
Exclusion Criteria:
- Patients with small cell lung cancer (including small cell carcinoma and non-small
cell carcinoma mixed lung cancer) and lung adenosquamous carcinoma mixed with squamous
carcinoma;
- Active brain metastases, cancerous meningitis, spinal cord compression, or imaging CT
or MRI screening for brain or pia mater disease (a patient with brain metastases who
have completed treatment and stable symptoms in 21 days before enrollment may be
enrolled, but should be confirmed by brain MRI, CT or venography evaluation as no
cerebral hemorrhage symptoms);
- Imaging (CT or MRI) shows that the distance between tumor lesion and the large blood
vessel is = 5 mm, or there is a central tumor that invades the local large blood
vessel and the distance between tumor and bronchial tree is = 2 cm; or there is a
significant pulmonary cavity or necrotizing tumor;
- Uncontrollable hypertension (systolic blood pressure =140 mmHg or diastolic blood
pressure =90 mmHg after optimal medical treatment);
- Suffering from severe cardiovascular disease: myocardial ischemia or myocardial
infarction above grade II, poorly controlled arrhythmias (including men with QTc
interval = 450 ms, women = 470 ms); according to NYHA criteria, grades III to IV
Insufficient function, or cardiac color Doppler ultrasound examination indicates left
ventricular ejection fraction (LVEF) <50%;
- Abnormal blood coagulation (INR > 1.5 or prothrombin time (PT) > ULN + 4 seconds or
APTT > 1.5 ULN), with bleeding tendency or undergoing thrombolytic or anticoagulant
therapy;
- Urine routine test protein =++, and confirmed 24 hours urine protein> 1.0 g;
- There is currently a peripheral neuropathy of =CTCAE 2 degrees, except for trauma;
- Respiratory syndrome (=CTC AE grade 2 dyspnea), serous effusion (including pleural
effusion, ascites, pericardial effusion) requiring surgical treatment;
- Long-term unhealed wounds or fractures;
- Serious infection (=CTC AE Level 2 infection) requiring systemic antibiotics;
decompensated diabetes or other ailments treated with high doses of glucocorticoids;
- Active or chronic hepatitis C or/and hepatitis B infection;
- Factors that have a significant impact on oral drug absorption, such as inability to
swallow, chronic diarrhea, and intestinal obstruction;
- Patients have undergone major surgery within 4 weeks before enrollment or have severe
trauma, fracture and ulcer;
- Severe weight loss (greater than 10%) within 6 weeks prior to enrollment;
- Clinically significant hemoptysis (daily hemoptysis greater than 50ml) within 3 months
prior to enrollment; or significant clinically significant bleeding symptoms or
defined bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric
ulcer, baseline fecal occult blood ++ and above, or suffering from vasculitis;
- Events of venous/ arterious thrombosis occurring within the first 12 months prior to
enrollment, such as cerebrovascular accidents (including transient ischemic attacks,
cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary
embolism;
- Patients have contraindication to platinum drugs (cisplatin/carboplatin) and cytotoxic
drug (Pemetrexed);
- Patients have anaphylactic reaction due to anlotinib Hydrochloride or the excipient in
investigational drug.
- Patients have anaphylactic reaction due to contrast agent;
- Planned for systemic anti-tumor therapy during the study period or within 4 weeks
prior to enrollment, including cytotoxic therapy, signal transduction inhibitors,
immunotherapy (or use mitomycin C within 6 weeks prior to receiving investigational
drug). Radiation-rehabilitation radiotherapy (EF-RT) was performed within 4 weeks
before enrollment or limited-field radiotherapy was performed for planned tumor
lesions within 2 weeks before enrollment.
- Patients were diagnosed with disease which will severely endanger the security of
patients or influence the completion of this research, or patients with other
situations are not suitable for the study according to the researchers.
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