Please select the eligibility criteria that correspond to the clinical trial below.
Title: LUX-Lung 6: A Randomized, Open-label, Phase III Study of BIBW 2992 Versus Chemotherapy as First-line Treatment for Patients With Stage IIIB or IV Adenocarcinoma of the Lung Harbouring an EGFR Activating Mutation
Brief 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


Options:
A: Inclusion criteria:

* Informed consent
* Histologically confirmed diagnosis of NSCLC, non epidermoid, stage IV or IIIB with pleural effusion, or N3 tumours not candidate for thoracic radiotherapy, harbouring deletions in the exon 19 or mutation in the exon 21 in the TK of the EGFR.
* Either measurable or evaluable disease.
* Age \> 18 years.
* ECOG performance status \< 2.
* Adequate bone marrow function
* Adequate renal function
* Adequate hepatic function
* Patients must be accessible for treatment and follow-up.
* Patients capable of following an adequate therapeutic compliance
* Women of child bearing potential: negative pregnancy test.
* Patients of both genders at a fertile age, including those women having their last menstruation within the two previous years, must follow effective contraceptive measures.
* Ability to swallow.
* Patients with asymptomatic brain metastasis and stable with medical treatment will be eligible for the study. Patients having received radiotherapy for their brain metastasis prior to the systemic treatment for the NSCLC will be also eligible.
* Absence of gastrointestinal tract problems

Exclusion criteria:

* Pregnant or lactating women.
* Women of child bearing potential having a positive pregnancy test in the basal visit or not accomplishing the test.
* Patients of both genders sexually active (at a fertile age) not following contraceptive measures during the study.
* Prior chemotherapy for metastatic disease. Both prior neoadjuvant and adjuvant chemotherapy allowed provided that completed â‰¥ 6 months before entering the study.
* Prior treatment with EGFR targeted therapies.
* Patients may have received radiotherapy, provided that the irradiated lesion is not the only evaluable lesion for response and completed before entering the study.
* Prior experimental pharmacological agent within the 3 weeks prior to the inclusion of the study.
* Any significant ophthalmologic impairment of the eye surface. Use of contact lenses is not recommended.
* Pre-existing motor or sensorial neurotoxicity grade \> 2, according to the NCI-CTC criteria.
* Evidence of spinal cord compression.
* Inability to take oral medication and surgical procedures affecting the absorption or implying intravenous or parenteral feeding.
* Any other severe disease or clinical conditions, as, but not only:

  * Unstable cardiopathy despite treatment, myocardial infarction within the 6 months before entering the study
  * History of significant neurological or psychiatric disorders, including dementia and epileptic seizures.
  * Uncontrolled active infection.
  * Uncontrolled peptic ulcer.
  * Unstable diabetes mellitus or any other contraindication for treatment with corticosteroids.
  * AST and/or ALT \> 1.5 x UNL associated to alkaline phosphatase \> 2.5 x UNL.
  * Any other underlying severe process affecting the ability to take part in the study.
* Absolute contraindication for steroids.
* Dementia or significant mental disorder interfering the understanding and giving the informed consent.
* History of other malignancy except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, radically treated prostatic carcinoma with good prognostic (Gleason = 6). History of other curatively treated malignancy and no evidence of disease within the past 5 years.
B: 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.
C: Inclusion Criteria:

1. Male or female, aged at least 18 years.
2. Pathologically confirmed adenocarcinoma of the lung.
3. Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy.
4. The tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R).
5. Mandatory provision of an unstained, archived tumour tissue sample in a quantity sufficient to allow for central analysis of EGFR mutation status.
6. Patients must be treatment-naïve for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with gefitinib or erlotinib as selected by the participating centre. Prior adjuvant and neo-adjuvant therapy is permitted(chemotherapy, radiotherapy, investigational agents).
7. Provision of informed consent prior to any study specific procedures, sampling, and analysis.
8. World Health Organization Performance Status of 0 to 1 with no clinically significant deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks

Exclusion Criteria:

1. Treatment with any of the following:

   * Prior treatment with any systemic anti-cancer therapy for locally advanced/metastatic NSCLC.
   * Prior treatment with an EGFR-TKI.
   * Major surgery within 4 weeks of the first dose of study drug.
   * Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug.
   * Patients currently receiving medications or herbal supplements known to be potent inducers of cytochrome P450 (CYP) 3A4.
   * Alternative anti-cancer treatment
   * Treatment with an investigational drug within five half-lives of the compound or any of its related material.
2. Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of study drug.
3. Spinal cord compression, symptomatic and unstable brain metastases, except for those patients who have completed definitive therapy, are not on steroids, have a stable neurologic status for at least 2 weeks after completion of the definitive therapy and steroids.
4. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
5. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of AZD9291.
6. Any of the following cardiac criteria:

   * Mean resting corrected QT interval (QTc) \>470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTcF value.
   * Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.
   * Any patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval.
7. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
8. Involvement in the planning and/or conduct of the study
D: Inclusion Criteria:

* Diagnosis of histologically or cytologically confirmed NSCLC, stage IIIb with documented malignant pleural effusion or stage IV
* Immunohistochemical evidence of EGFR expression on tumor tissue
* Presence of at least 1 bi-dimensionally measurable index lesion, whereby index lesions must not lie in an irradiated area

Exclusion Criteria:

* Previous exposure to monoclonal antibodies, signal transduction inhibitors or EGFR-targeting therapy
* Previous chemotherapy for NSCLC
* Documented or symptomatic brain metastasis
* Superior vena cava syndrome contra-indicating hydration
* Previous malignancy in the last 5 years except basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix

Answer: B