Clinical trial NCT02691871 (phase 1, status: unknown status)
Conditions: lung adenocarcinoma
ICD codes: D02.20, D02.21, D02.22
Drugs: apatinib (250 mg/d) + docetaxel (60 mg/m2), apatinib (500 mg/d) + docetaxel (60 mg/m2), apatinib (750 mg/d) + docetaxel (60 mg/m2)
SMILES: [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1, [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1, [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1
Eligibility criteria:

        Inclusion Criteria:

          1. 18 years to 65 years;

          2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1;

          3. Life expectancy of more than 12 weeks;

          4. At least one measurable lesion according to RECIST 1.1 which has not received
             radiotherapy =< 3 months;

          5. Histologically/cytologically confirmed advanced/metastatic lung adenocarcinoma of
             stage IV with documented wild-type EGFR;

          6. Patients with one prior platinum-containing chemotherapy. In case of recurrent
             disease, one additional prior regimen is allowed for adjuvant and/or neoadjuvant
             therapy.

          7. Adequate hepatic, renal, heart, and hematologic functions: ANC ≥ 1.5×109/L, PLT ≥
             100×109/L, HB ≥ 90 g/L, TBIL ≤ 1.5×ULN, ALT or AST ≤ 2.5×ULN (or ≤ 5×ULN in patients
             with liver metastases), Serum Cr ≤ 1×ULN, Cr clearance ≥ 50 mL/min, INR < 1.5 or PT <
             ULN+4s or APTT < 1.5×ULN, proteinuria < (++) or urinary protein ≤ 1.0 g/24 hrs;

          8. For women of child-bearing age, the pregnancy test results (serum or urine) within 7
             days before enrolment must be negative. They will take appropriate methods for
             contraception during the study until the 8th week post the last administration of
             study drug. For men (previous surgical sterilization accepted), will take appropriate
             methods for contraception during the study until the 8th week post the last
             administration of study drug.

          9. Signed informed consent.

        Exclusion Criteria:

          1. Accumulation of coelomic fluid (e.g. pleural effusion, ascites fluid, cardiac
             effusion) requiring treatment;

          2. Other malignancy within the past five years other than basal cell skin cancer, or
             carcinoma in situ of the cervix;

          3. Factors affecting the oral medication (e.g. inability to swallow, chronic diarrhea and
             intestinal obstruction);

          4. Major injuries and/or surgery =< 4 weeks prior to registration with incomplete wound
             healing. Patients who have received radiotherapy (except local palliative
             radiotherapy), chemotherapy, molecular targeted therapy =< 3 weeks, or
             nitrosoureas/mitomycin chemotherapy =< 6 weeks prior to registration;

          5. Patients with poor-controlled arterial hypertension (systolic pressure ≥ 140 mmHg
             and/or diastolic pressure ≥ 90 mm Hg) despite standard medical management;

          6. Suffered from grade II or above myocardial ischemia or myocardial infarction,
             uncontrolled arrhythmias (including QT interval male ≥ 450 ms, female ≥ 470 ms). Grade
             III-IV cardiac insufficiency according to NYHA criteria or echocardiography check:
             LVEF<50%;

          7. History of clinically significant haemoptysis =< 2 months (more than half of one tea
             spoon of fresh blood per day) prior to registration. Coagulation disfunction,
             hemorrhagic tendency or receiving anticoagulant therapy;

          8. History of clinically relevant major bleeding event (e.g. gastrointestinal hemorrhage,
             bleeding ulcer, occult blood ≥ (++), and vasculitis) =< 3 months prior to
             randomization;

          9. Patients who have active brain metastases or leptomeningeal disease. Patients with
             treated brain metastases are eligible if they are clinically stable with regard to
             neurologic function, off steroids after cranial irradiation ending at least 3 weeks
             prior to randomization, or after surgical resection performed at least 3 weeks prior
             to randomization. No evidence of Grade greater than or equal to 1 CNS hemorrhage based
             on pretreatment CT or MRI scan;

         10. Centrally located tumors of local invasion of major blood vessels, or distinct
             interstitial lung disease by the chest radiographic findings (CT or MRI);

         11. Treatment with other investigational drugs or other anti-cancer therapy;

         12. Previous therapy with other VEGFR inhibitors (other than bevacizumab);

         13. Previous therapy with docetaxel =< 6 months prior to registration;

         14. Treatment in another investigational trial =< 4 weeks prior to registration;

         15. Any contraindications for therapy with docetaxel. History of severe hypersensitivity
             reactions to docetaxel or other drugs formulated with polysorbate 80 (Tween 80).
             History of hypersensitivity to apatinib and/or the excipients of the trial drugs;

         16. Active or chronic hepatitis C and/or B infection, or other active uncontrolled
             infection;

         17. History of immunodeficiency disease (including HIV positive), concurrent acquired or
             congenital immunodeficiency syndrome, or history of organ transplantation;

         18. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             =< 6 months prior to registration;

         19. History of arterial or venous thromboembolic events (e.g. CVA, DVT and pulmonary
             embolism) =< 12 months prior to randomization;

         20. Administration of strong/potent cytochrome P450 (CYP)3A4 inhibitors within 7 days, or
             inducers within 12 days;

         21. 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;

         22. History of mental diseases;

         23. Other conditions regimented at investigators' discretion.