BIBW 2992 (Afatinib) vs Gemcitabine-cisplatin in 1st Line Non-small Cell Lung Cancer (NSCLC)
Condition: Carcinoma, Non-Small-Cell Lung; Adenocarcinoma
MeSH terms: Adenocarcinoma; Carcinoma, Non-Small-Cell Lung
Intervention: Gemcitabine+Cisplatin; BIBW 2992
Intervention description: Gemcitabine d1,8, Cisplatin d1, 21 days as a course, up to 6 courses.; starting dose is 40 mg, in the event of no or minimal drug-related adverse events after one course, the dose will be increased to 50mg. in the event of certain drug related Adverse Event (AE), dose reduction will be increments of 10 mg, with the lowest dose being 20mg.
Intervention MeSH terms: Gemcitabine; Afatinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 364.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      To investigate the efficacy and safety of BIBW 2992 compared to standard first-line
      chemotherapy in patients with stage IIIB or IV adenocarcinoma of the lung harbouring an EGFR
      activating mutation
    

Eligibility criteria:

        Inclusion criteria:

          1. pathologically confirmed diagnosis of stage IIIB or stage IV adenocarcinoma of the
             Lung

          2. EGFR(Epidermal Growth Factor Receptor) mutation detected by central laboratory
             analysis of tumor biopsy material

          3. Measurable disease according to Response Evaluation Criteria in Solid Tumours
             (RECIST)1.1

          4. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.

          5. Age>=18 years

          6. life expectancy of at least three months

          7. Written informed consent that is consistent with International Conference on
             Harmonisation-Good Clinical Practice (ICH-GCP) guidelines.

        Exclusion criteria:

          1. Prior chemotherapy for relapsed and/or metastatic NSCLC.

          2. Prior treatment with EGFR targeting small molecules or antibodies.

          3. Radiotherapy or surgery(other than biopsy) within 4 weeks prior to randomization

          4. Active brain metastases

          5. Any other current malignancy or malignancy diagnosed within the past 5 years

          6. Known pre-existing interstitial lung disease

          7. Significant or recent acute gastrointestinal disorders with diarrhoea as a a major
             symptoms.

          8. History or presence of clinically relevant cardiovascular abnormalities

          9. Cardiac left ventricular function with resting ejection fraction of less than 50%.

         10. Any other concomitant serious illness or organ system dysfunction which in the opinion
             of the investigator would either compromise patient safety or interfere with the
             evaluation of the safety of the test drug.

         11. Absolute neutrophil count(ANC)<1500/mm3

         12. Platelet count<100,000/mm3

         13. Creatinine clearance<60ml/min or serum creatinine>1.5 times Upper Limit of Normal
             (ULN).

         14. Bilirubin>1.5 times ULN

         15. Aspartate Amino Transferase (AST) or Alanine Amino Transferase (ALT) > 3 times ULN

         16. Women of childbearing potential, or men who are able to father a child, unwilling to
             use a medically acceptable method of contraception during the trial

         17. Pregnancy of breast-feeding

         18. Patients unable to comply with the protocol

         19. Active hepatitis B infection, active hepatitis C infection or known HIV(Human
             Immunodeficiency Virus) carrier.

         20. Known or suspected active drug or alcohol abuse.

         21. requirement for treatment with any of the prohibited concomitant medications listed in
             section 4.2.2

         22. Any contraindications for therapy with gemcitabine/cisplatin

         23. Known hypersensitivity to BIBW2992 or the excipient of any of the trial drugs

         24. Use of any investigational drug within 4 weeks of randomization.