apatinib in the treatment of patients with egfr t790m-negative nsclc

Conditions: Lung Diseases; Neoplasms; Respiratory Tract Diseases; Thoracic Neoplasms; Non-Small-Cell Lung

Summary: this phase 2 study is designed to evaluate the safety and activity of apatinib,a tyrosine kinase inhibitor that selectively inhibits the vascular endothelial growth factor receptor-2, in combination with egfr-tki in nsclc with t790m-negative after the failure of egfr-tki therapy.


Eligibility criteria:
inclusion criteria: * pathologically confirmed stage iiib, iv non-squamous non-small cell lung cancer, with measurable lesions (the long axis of tumor lesions ≥ 10mm with ct, the short axis of lymph node lesions ≥ 15mm with ct, the lesions not receive radiotherapy, frozen or other local treatment); * patients with slow progression on first-line egfr tki(erlotinib / icotinib / gefitinib) treatment; * no t790m mutation including an assessment from tumor biopsy obtained while on or subsequent to the most recent egfr tki therapy; * eastern cooperative oncology group (ecog) performance status 0-2; * life expectancy of more than 3 months; * adequate bone marrow function: wbc ≥ 3.0 ×10 e+9/l, neutrophil ≥ 1.5 × 10 e+9/l, platelets ≥ 80 × 10e+9/l,hb ≥ 10.0g/dl;a total bilirubin (tbil) of ≤1.5 upper normal limitation (unl), a alanine aminotransferase (alat) and aspartate aminotransferase (asat) of ≤3unl or ≤5unl in case of liver metastasis, a creatinine (cr) of ≤ 1.5 unl; a creatinine clearance rate ≥ 50ml/min (cockcroft-gault); * female subjects of child-bearing potential must agree to use contraceptive measures starting 1 week before the administration of the first dose of apatinib until 8 weeks after discontinuing study drug. male subjects must agree to use contraceptive measures during the study and 8 weeks after last dose of study drug; * the participants volunteered to join this study should sign the informed consent forms, have better compliance in the follow-up; exclusion criteria: * squamous cell carcinoma (including adenosquamous carcinoma); small cell lung carcinoma (including small cell carcinoma and non-small cell mixed lung carcinoma); * active brain metastases, cancerous meningitis, patients with spinal cord compression; * rapid progression of the disease or cancer invades vital organs; * the distance between the tumor lesion and the large blood vessel is less than 5 mm, or there is a central tumor invading local macrovascular; * obvious pulmonary cavity or tumor necrosis; * uncontrollable high blood pressure; * grade ⅱ or above myocardial ischemia or myocardial infarction or arrhythmia control is not good,ⅲ \~ ⅳ grade cardiac insufficiency, or cardiac ultrasonography showed left ventricular ejection fraction (lvef) \<50% according to the nyha standard; * have a history of interstitial lung disease or patients with interstitial lung disease; * coagulation abnormalities (inr\> 1.5 or pt\> uln + 4s or aptt\> 1.5 uln) with bleeding tendency or undergoing thrombolytic or anticoagulant therapy; * there was significant hemoptysis within 2 months prior to enrollment, or a daily hemoptysis volume is 2.5 ml or above; * a clinically significant bleeding symptom or bleeding tendencies such as gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal occult blood ++ and above, or vasculitis that occurred within 3 months prior to enrollment; * aneurysm / venous thrombotic events such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism; * arterial / venous thrombotic events such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism within 12 months prior to enrollment; * hereditary or acquired bleeding and thrombophilia, such as hemophilia, coagulopathy, thrombocytopenia, hypersplenism； * long-term unhealed wounds or fractures; * major surgery or severe traumatic injury, fracture or ulcer within 4 weeks prior to enrollment; * unable to swallow, chronic diarrhea or intestinal obstruction; * abdominal fistula, gastrointestinal perforation or abdominal abscess within 6 months prior to enrollment; * urinary protein ≥ ++, 24-hour urinary protein ≥ 1.0 g; * active infections require antimicrobial treatment; * alk gene abnormalities (gene fusion or mutation occurred); * pregnant or lactating women, or women unwilling or unable to take effective contraception;

Keywords: apatinib t790 negative nsclc