BIBF 1120 + Docetaxel (Japan) in Patients With Advanced Non-small-cell Lung Cancer, Phase I

A Phase I Study of Continuous, Concomitant Oral Treatment With BIBF 1120 and Docetaxel - a Phase I, Open-label, Dose-escalation Study in Japanese Patients With Stage IIIB/IV or Recurrent Non-small-cell Lung Cancer After Failure of Chemotherapy

To confirm the safety of BIBF 1120 at a dose level up to 200 mg x 2/day (i.e., overseas recommended Phase III dose for combination treatment) with standard therapy of docetaxel (60 mg/m2 and 75 mg/m2) in Japanese advanced non small cell lung cancer (NSCLC) patients with stage IIIB/IV or recurrent after failure of first line chemotherapy and to determine the recommended dose for the Phase II trial.

Inclusion criteria:

1. Histologically/cytologically confirmed, locally advanced/metastatic NSCLC of stage IIIB/IV or recurrent NSCLC (all histologies. Existence or nonexistence of measurable lesion according to RECIST is no object.)

2. Patients with one prior chemotherapy regimen including platinum-containing drug.

   In case of recurrent disease, one additional prior regimen is allowed for adjuvant and/or neoadjuvant therapy. However monotherapy of EGFR-TKI (i.e. erlotinib/Tarceva® and gefitinib/Iressa®) is not counted as 'one regimen'.

3. Male or female patients age >=20 years and =<74 years at the enrolment.

4. Life expectancy of at least three (3) months after the start of administration of the investigational drug.

5. Eastern Cooperative Oncology Group (ECOG) [R01-0787] performance Score 0 or 1.

6. Patients retaining a significant physiological compensatory function and patients with sufficient baseline organ function as follows:

   • Haemoglobin count more than 9.0g/dL
   • Absolute neutrophil count more than 1500/mm3
   • Platelet count more than 100 000/mm3
   • Serum creatinine less than or equal to1.5x upper limit of normal range at the investigator site
   • Aspartate aminotransferase (AST) and / or alanine aminotransferase (ALT) less than or equal to 1.5x upper limit of normal range at the investigator site (It is the same if patients have liver metastases)
   • PaO2 or SpO2 more than 60torr or 92%

7. Written informed consent that is consistent with ICH-GCP guidelines.

Exclusion criteria:

1. Patients who have received chemotherapy (including other investigational drug), hormonal therapy and immune therapy =<4 weeks prior to registration or who have not recovered from side effects of such therapy.
2. Patients who have received radiotherapy =<4 weeks (limited field (e.g brain or bone metastasis) radiation =<2 weeks) prior to registration.
3. Patients who have active brain metastases. (Patients who have no symptoms and is not needed to receive therapy in the registration may participate in this trial)
4. Patients with active double cancer. (Patients who have skin cancer that is not malignant melanoma and carcinoma in situ of uterine cervix may participate in this trial)
5. Patients with distinct / suspected pulmonary fibrosis or interstitial lung disease by the chest radiographic findings, or patients with a previous history of.
6. History of clinically significant haemoptysis within the past 3 months (more than one tea spoon of fresh blood per day)
7. Therapeutic anticoagulation (except low dose heparin and/or heparin flush as needed for maintenance of an indwelling intravenous device) or antiplatelet therapy (except for chronic low-dose therapy with acetylsalicylic acid =<325 mg per day)
8. History of major thrombotic or clinically relevant major bleeding event in the past 6 months prior to registration.
9. Known inherited predisposition to bleeding or thrombosis.
10. Significant cardiovascular diseases. (i.e. hypertension not controlled by medical therapy, unstable angina, history of myocardial infarction within the past 6 months, congestive heart failure > NYHA II, serious cardiac arrhythmia, pericardial effusion)
11. Significant weight loss (> 10 %) within the past 6 weeks prior to registration in the this trial
12. Current peripheral neuropathy >= CTCAE grade 2 except due to trauma.
13. Accumulation of coelomic fluid (e.g. pleural effusion, ascites fluid, cardiac effusion) requiring treatment
14. Major injuries and/or surgery within the past 10 days prior to registration with incomplete wound healing.
15. Serious infections requiring systemic antibiotic (e.g antiviral, antimicrobial, antifungal) therapy.
16. Decompensated diabetes mellitus or other contraindication to high dose corticosteroid therapy.
17. Gastrointestinal disorders or abnormalities (e.g Crohn's disease, Colitis ulcerosa and extensive gastrectomy) that would interfere with absorption of the study drug.
18. Patients with difficulty in swallowing study medication
19. Patients with positive HBs antigen, HCV antibody, or HIV antibody test
20. Serious illness or concomitant non-oncological disease such as neurologic-, psychiatric-, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with trial participation or investigational drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the trial.
21. Patients who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner for participating females, condoms for participating males) during the trial and for at least 12 months after end of active therapy
22. Female patients who are pregnant, breast feeding and may become pregnant.
23. Patients who have or is suspected of having active alcohol or drug abuse.
24. Patient with clinically meaningful drug hypersensitivities.
25. Patients with auto immune disease.
26. Patients unable to comply with the protocol.
27. Other patients judged ineligible for enrolment in the study by the investigator.