Clinical trial NCT02590965 (phase 2, status: completed)
Conditions: non-small cell lung cancer
ICD codes: C78.00, C78.01, C78.02, D14.30, D14.31, D14.32, C34.2
Drugs: fruquintinib, placebo
SMILES: CNC(=O)C1=C(C)OC2=CC(OC3=NC=NC4=CC(OC)=C(OC)C=C34)=CC=C12, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
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.