a study of famitinib plus docetaxel in patients with advanced non-squamous and non-small cell lung cancer (nsclc)

Conditions: Non-Small Cell Lung Cancer (NSCLC)

Summary: famitinib is a tyrosin-inhibitor agent targeting at c-kit, vegfr2, pdgfr, vegfr3, flt1 and flt3. phase i study has shown that the toxicity is manageable. this study assessed the safety and maximum tolerated dose of continuous daily treatment with famitinib plus docetaxel (60 mg/m\^2, every 3 weeks) in patients with advanced non-squamous and non-small cell lung cancer (nsclc) to determine the recommended dose for the phase ii trial.


Eligibility criteria:
inclusion criteria: 1. age:18-70 years; 2. ecog ps (eastern cooperative oncology group performance status)of 0 or 1; 3. life expectancy of at least 12 weeks; 4. histologically or cytologically confirmed, locally advanced and/or metastatic nsclc of stage iiib or iv or recurrent nsclc; 5. relapse or failure of one first line prior platinum-based chemotherapy;egfr mutation type previously treated with platinum-based chemotherapy and egfr inhibitors; 6. 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; 7. 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 \ 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 8. 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; 9. patient has given written informed consent. exclusion criteria: 1. more than one chemotherapy treatment regimen (except,either neoadjuvant or adjuvant or neoadjuvant plus adjuvant) for advanced and/or metastatic or recurrent nsclc; 2. previous therapy with other vegfr inhibitors (including sunitinib,sorafenib,pazopanib,axitinib,other than bevacizumab) or docetaxel for treatment of nsclc; 3. radiographical evidence of cavitary or necrotic tumours; 4. centrally located tumours with radiographical evidence (ct or mri) of local invasion of major blood vessels; 5. pre-existing ascites and/or clinically significant pleural effusion; 6. pulmonary hemorrhage/ bleeding event ≥ ctcae gr. 2 before initiating investigational drugs; 7. history of clinically significant haemoptysis within the past 3 months（24h \>half teaspoon）; 8. current peripheral neuropathy greater than ctcae grade 2; 9. other malignancy within the past 3 years other than basal cell skin cancer, or carcinoma in situ of the cervix; 10. active brain metastases (such as stable time ≤ 4 weeks,no radiotherapy treatment,any symptoms,or seizures treatment needing) or leptomeningeal disease.; 11. 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; 12. persistence of clinically relevant therapy related toxicities from previous chemotherapy and/or radiotherapy; 13. 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.; 14. 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); 15. urine protein ≥ + + and confirmed the 24-hour urinary protein\>1.0 g; 16. history of major thrombotic or clinically relevant major bleeding event in the past 6 months，and known inherited predisposition to bleeding or thrombosis; 17. pt or aptt bias from normal range≥50%; 18. 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; 19. preexisting thyroid dysfunction, even using medical therapy, thyroid function cannot maintain in the normal range; 20. diabetes mellitus can not controlled with hypoglycemic agent; 21. active or chronic hepatitis c and/or b infection with liver dysfunction; 22. history of immunodeficiency disease, concurrent acquired or congenital immunodeficiency,or history of organ transplantation; 23. serious infections requiring systemic antibiotic therapy; 24. variety of factors that affect the oral medication (such as inability to swallow, gastrointestinal resection, chronic diarrhea and intestinal obstruction); 25. significant weight loss (\>10 %) within the past 6 months; 26. pregnancy , breast feeding or child bearing potential, a positive urine or serum pregnancy test result 7 days before initiating famitinib; 27. active alcohol or drug abuse; 28. 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; 29. psychological, familial, sociological, or geographical factors potentially hampering compliance with the study protocol and follow-up schedule; 30. patients unable to comply with the protocol; 31. 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.