a clinical trial of fruquintinib in patients with advanced non-small cell lung cancer

Conditions: Non-small Cell Lung Cancer

Summary: this is a randomized, double-blind, placebo-controlled, multi-center phase ii clinical trial to evaluate the efficacy and safety of fruquintinib plus best supportive care in patients with advanced non-squamous non-small cell lung cancer who failed to second-line standard chemotherapy.

approximately 90 subjects will be randomized to fruquintinib plus best supportive care or placebo plus best supportive care at a 2:1 ratio. randomization will be stratified by egfr (epidermal growth factor receptor) gene status: mutant vs. wild type vs. unknown. all subjects will receive fruquintinib/placebo for consecutive 3 weeks, followed by one-week rest. a treatment cycle consists of 4 weeks. tumor assessment will be performed every 4 weeks in the first 3 cycles, and every 8 weeks since the 4th cycle, until disease progression. further treatment and survival follow-up after progression will be recorded.

Eligibility criteria:
inclusion criteria: 1. fully understand the study and sign the informed consent form voluntarily; 2. histologically and/or cytologically diagnosed with local advanced and/or metastatic stage iiib/iv non-squamous nsclc; 3. previously failed to two chemotherapy regimens(treatment failure is defined as disease progression or intolerable toxicity), patients with positive egfr mutation permitted to treated by egfr-tki previously; patients with egfr wild type or unknown whether or not treated by egfr-tki previously; 4. aged 18-75 years (inclusive); 5. body weight ≥40 kg; 6. evident measurable lesion(s) (according to recist1.1); 7. ecog performance status 0-1; 8. expected survival \>12 weeks exclusion criteria: 1. treatment in another clinical trials in the past 3 weeks; or treatment with systemic anti-tumor chemotherapy, radiotherapy or biotherapy within 3 weeks prior to administration of the study drug; 2. previous therapy with vegf/vegfr inhibitors; 3. unrecovered from toxicity caused by previous anti-cancer treatment (ctcae \>grade 1), or not completely recovered from previous surgery; 4. previous active brain metastasis (without radiotherapy previously, or symptoms stable \< 4 weeks, or with clinical symptoms, or with medication to control symptoms); 5. other malignancies except basal cell carcinoma or cervical carcinoma in situ in the past 5 years; 6. uncontrolled clinical active infection, e.g. acute pneumonia and active hepatitis b; 7. dysphagia or known drug malabsorption; 8. present active duodenal ulcer, ulcerative colitis, intestinal obstruction and other gastrointestinal diseases or other conditions that may lead to gastrointestinal bleeding or perforation according to the investigators' judgment; or with a history of intestinal perforation or intestinal fistula; 9. have evidence or a history of thrombosis or bleeding tendency, regardless of seriousness; 10. stroke and/or transient ischemic attack within 12 months prior to enrollment; 11. appropriate organ function. patients with any of the following conditions will be excluded: * absolute neutrophil count (anc) \<1.5×109/l, platelet \<100×109/l or hemoglobin \<9 g/dl within 1 week prior to enrollment; * serum total bilirubin \>1.5 upper limit of normal (uln), alanine transaminase and aspartate transferase \>1.5×uln; alt and ast \> 3×uln in patients with liver metastasis; * electrolyte abnormality of clinical significance; * blood creatinine \>uln and creatinine clearance \<60 ml/min; * urine protein 2+ or above, or 24 h urine protein quantification ≥1.0 g/24 h; * activated partial thromboplastin time (aptt) or/and inr and prothrombin time (pt) \>1.5×uln (according to reference range in each clinical study center); 12. uncontrolled hypertension, systolic blood pressure ≥140 mmhg and/or diastolic blood pressure ≥90 mmhg with medication; or heart failure nyha classification ≥ grade 2; 13. heart function evaluation: left ventricular ejection fraction \<50% (echocardiography); 14. acute myocardial infarction, severe/unstable angina or coronary bypass surgery within 6 months prior to enrollment; history of arterial thrombosis or deep venous thrombosis; 15. skin wound, surgical site, wound site, severe mucosal ulcer or fracture without complete healing; 16. female subjects who are pregnant or lactating or of child bearing potential with positive pregnancy test result before the first dose; 17. patients with child bearing potential who or whose sexual partners are not willing to take contraceptive measures; 18. any clinical or laboratory abnormalities unfit to participate in this clinical trial according to the investigator's judgment; 19. serious psychological or psychiatric disorders which may affect subject compliance in this clinical study; 20. allergy to fruquintinib and/or excipient contained in trial drugs.