Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Double-blind, Randomised Study to Assess the Safety and Efficacy of AZD9291 Versus a Standard of Care Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor as First Line Treatment in Patients With Epidermal Growth Factor Receptor Mutation Positive, Locally Advanced or Metastatic Non Small Cell Lung Cancer.
Brief Summary: To assess the efficacy and safety of AZD9291 versus a standard of care epidermal growth factor receptor tyrosine kinase inhibitor in patients with locally advanced or Metastatic Non Small Cell Lung Cancer


Options:
A: Inclusion Criteria:

* Histologically confirmed NSCLC and willing to provide paraffin embedded tumour tissue
* NSCLC - locally advanced (Stage IIIB) or metastatic (stage IV) disease, not amenable to curative surgery or radiotherapy chemonaïve, life expectancy of 12 weeks
* WHO Performance status \<= 2

Exclusion Criteria:

* Newly diagnosed CNS metastases
* Less than 4 weeks since completion of radiotherapy or persistence of any radiotherapy related toxicity.
* Hypersensitivity to ZD1839 or intravenous vinorelbine
* Prior treatment with EGFR inhibitors
* Other co-existing malignancies
* ALT/AST \>2.5 x ULRR
* ANC \< 2.0 x 10\^9/L or platelets \< 100 x 10\^9/L
B: Inclusion Criteria:

* Recurrent or progressive Non-Small Cell Lung Cancer stage IV or IIIB patients.
* Positive EGFR Mutation.
* No previous systemic anticancer therapy.
* Measurable lesion according to RECIST with at least one measurable lesion not previously irradiated, unless disease progression has been documented at that site.
* Provision of written informed consent.

Exclusion Criteria:

* Experience of Anti-EGFR(the epidermal growth factor receptor) Monoclonal Antibody or small molecular compounds therapy such as gefitinib, erlotinib or Cetuximab.
* Evidence of clinically active Interstitial Lung Diseases (Patients with chronic, stable, radiographic changes who are asymptomatic need not be excluded).
* Known severe hypersensitivity to icotinib or any of the excipients of this product.
* Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the study.
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:

* 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.

Answer: C