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.
Name: Apatinib
Name: EGFR-TKI
Description: the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse
Measure: Progression-free survival (PFS) Time: up to 24 monthsDescription: The length of time from either the date of diagnosis or the start of treatment that half of the patients in a group of patients diagnosed with the disease are still alive.
Measure: Overall survival (OS) Time: up to 36 monthsDescription: From first response to the date of first documented disease progression
Measure: Duration of response (DOR) Time: up to 24 monthsDescription: the proportion of patients with a best overall response of CR, PR or SD in the whole body, as assessed per RECIST 1.1 by the investigator.
Measure: Disease Control Rate (DCR) Time: 24 weeksDescription: the proportion of patients with a best overall confirmed response of CR or PR in the whole body as assessed per RECIST 1.1 by the investigator
Measure: Overall response rate (ORR) Time: 24 weeksDescription: Analysis of changes from baseline using the quality of life (QoL) instrument
Measure: the quality of life (QoL) Time: up to 36 monthsAllocation: Randomized
Parallel Assignment
There is one SNP
A Randomized, Controlled Phase II Clinical Trial of Apatinib in Combination With EGFR-TKI Versus EGFR-TKI for Non-squamous, Non-small Cell Lung Cancer(NSCLC) With T790M-negative After the Failure of EGFR-TKI Therapy. --- T790M ---
Apatinib in the Treatment of Patients With EGFR T790M-Negative NSCLC 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. --- T790M ---
Apatinib in the Treatment of Patients With EGFR T790M-Negative NSCLC 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. --- T790M --- --- T790M ---
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. --- T790M ---
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; 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. --- T790M ---