A Study of Famitinib Plus Docetaxel in Patients With Advanced Non-squamous and Non-Small Cell Lung Cancer (NSCLC)

Inclusion criteria

• Age:18-70 years;
• ECOG PS (Eastern Cooperative Oncology Group Performance Status)of 0 or 1;
• Life expectancy of at least 12 weeks;
• Histologically or cytologically confirmed, locally advanced and/or metastatic NSCLC of stage IIIB or IV or recurrent NSCLC;
• Relapse or failure of one first line prior platinum-based chemotherapy;EGFR mutation type previously treated with platinum-based chemotherapy and EGFR inhibitors;
• At least one target tumour lesion that has not been irradiated within the past 3 months and that can accurately be measured ,according to RECIST 1.1;
• Participants have adequate organ and marrow function as defined below:

• Hemoglobin ≥ 90g/L ( no blood transfusion in 2 weeks)
• Absolute neutrophil count (ANC) ≥ 1.5×10^9/L
• Platelets(PLT)≥ 100×10^9/L
• Bilirubin < 1.25×ULN(Upper Limit Of Normal)
• ALT < 2.5×ULN; ALT < 5×ULN ( If have liver metastases)
• AST < 2.5×ULN; AST < 5×ULN ( If have liver metastases)
• Serum creatinine < 1.25×ULN, and endogenous Cr clearance > 45 ml/min(Cockcroft-Gault Formula)
• Cholesterol ≤ 1.5×ULN and triglyceride≤ 2.5×ULN
• Left ventricular ejection fraction(LVEF): ≥ LLN(Lower Limit Of Normal) by Color Doppler Ultrasonography
• Female: Child bearing potential, a negative urine or serum pregnancy test result 7 days before initiating famitinib.All subjects who are not surgically sterile or postmenopausal must agree and commit to the use of a reliable method of birth control for the duration of the study and for 8 weeks after the last dose of test article. Male: All subjects who are not surgically sterile or postmenopausal must agree and commit to the use of a reliable method of birth control for the duration of the study and for 8 weeks after the last dose of test article;
• Patient has given written informed consent.

Exclusion criteria

• More than one chemotherapy treatment regimen (except,either neoadjuvant or adjuvant or neoadjuvant plus adjuvant) for advanced and/or metastatic or recurrent NSCLC;
• Previous therapy with other VEGFR inhibitors (including sunitinib,sorafenib,pazopanib,axitinib,other than bevacizumab) or docetaxel for treatment of NSCLC;
• Radiographical evidence of cavitary or necrotic tumours;
• Centrally located tumours with radiographical evidence (CT or MRI) of local invasion of major blood vessels;
• Pre-existing ascites and/or clinically significant pleural effusion;
• Pulmonary hemorrhage/ bleeding event ≥ CTCAE gr. 2 before initiating investigational drugs;
• History of clinically significant haemoptysis within the past 3 months（24h >half teaspoon）;
• Current peripheral neuropathy greater than CTCAE grade 2;
• Other malignancy within the past 3 years other than basal cell skin cancer, or carcinoma in situ of the cervix;
• Active brain metastases (such as stable time ≤ 4 weeks,no radiotherapy treatment,any symptoms,or seizures treatment needing) or leptomeningeal disease.;
• Treatment with other investigational drugs or other anti-cancer therapy, or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with this trial;
• Persistence of clinically relevant therapy related toxicities from previous chemotherapy and/or radiotherapy;
• Treatment with cytotoxic drugs, radiotherapy(except extremities and brain) , immunotherapy , monoclonal antibody, or TKI inhibitor therapy within the past 4 weeks, being previous anti-cancer treatment interval ≤ 4 weeks.;
• Patients with hypertension using combination therapy (systolic blood pressure>140 mmHg, diastolic blood pressure>90 mmHg). Patients with unstable angina, myocardial ischemia or myocardial infarction in the past 6 months, congestive heart failure>NYHA II,and arrhythmia (including QTcF interval ≥ 450ms for male and 470ms for female);
• Urine protein ≥ + + and confirmed the 24-hour urinary protein>1.0 g;
• History of major thrombotic or clinically relevant major bleeding event in the past 6 months，and known inherited predisposition to bleeding or thrombosis;
• PT or APTT bias from normal range≥50%;
• 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) ， low-dose aspirin (less than 100mg daily) is allowed;
• Preexisting thyroid dysfunction, even using medical therapy, thyroid function cannot maintain in the normal range;
• Diabetes mellitus can not controlled with hypoglycemic agent;
• Active or chronic hepatitis C and/or B infection with liver dysfunction;
• History of immunodeficiency disease, concurrent acquired or congenital immunodeficiency,or history of organ transplantation;
• Serious infections requiring systemic antibiotic therapy;
• Variety of factors that affect the oral medication (such as inability to swallow, gastrointestinal resection, chronic diarrhea and intestinal obstruction);
• Significant weight loss (>10 %) within the past 6 months;
• Pregnancy , breast feeding or child bearing potential, a positive urine or serum pregnancy test result 7 days before initiating famitinib;
• Active alcohol or drug abuse;
• Any contraindications for therapy with docetaxel；History of severe hypersensitivity reactions to docetaxel or other drugs formulated with polysorbate 80 (Tween 80)；Hypersensitivity to famitinib and/or the excipients of the trial drugs；Hypersensitivity to contrast media;
• Psychological, familial, sociological, or geographical factors potentially hampering compliance with the study protocol and follow-up schedule;
• Patients unable to comply with the protocol;
• Evidence of significant medical illness that in the investigator's judgment will substantially increase the risk associated with the subject's participation in and completion of the study.