Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Placebo-controlled, Double-blind Phase III Study of the Effect of First-line Treatment With Intercalated Tarceva Versus Placebo in Combination With Gemcitabine/Platinum on Progression-free Survival in Patients With Stage IIIB/IV Non-small Cell Lung Cancer
Brief Summary: This 2 arm study will compare the efficacy and safety of sequential treatment with Tarceva or placebo, plus platinum-based therapy, as first line treatment in patients with advanced or recurrent non-small cell lung cancer. Patients will be randomized to receive gemcitabine (1250mg/m2 iv) on days 1 and 8, and cisplatin (75mg/m2) or carboplatin (5xAUC)on day 1, followed by Tarceva 150mg/day or placebo from day 15 to day 28 of each 4 week cycle for a total of 6 cycles,then followed by Tarceva or placebo monotherapy.The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.


Options:
A: Inclusion Criteria:

1. Stage IIIB (cytological confirmed with malignant pleural effusion or pericardial effusion) or histopathological or cytological confirmed stage IV NSCLC or relapsed after complete resection .
2. EGFR exon19 deletions or exon 21 L858R mutation by the DNA direct PCR sequencing using fresh tumor sample or paraffin embed tumor sample.
3. Measurable lesions as defined by RECIST criteria .
4. Palliative radiotherapy allowed if it was finished 3 weeks after the first drug administration, but the target lesions should not be included in the radiotherapy field.
5. Patients with operation are allowed if the operation is 4 weeks before the first drug administration
6. Men or women of at least 18 years of age.
7. ECOG Performance status of 0 to 2.
8. Estimated life expectancy of at least 12 weeks.
9. Patient compliance and geographic proximity that allow adequate follow-up.
10. Adequate organ function tested 7 days before the first drug administration:

    hemoglobin ≥9 g/dL,absolute neutrophil count (ANC) ≥1.5\*109/L, platelets ≥100 \*109/L,bilirubin ≤1.5ULN, alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 upper limited number(ULN) (AP, AST, ALT ≤5ULN is acceptable if liver has tumor involvement).INR≤1.5, APTT in the normal range( 1.2DLN-1.2ULN),creatinine ≤1.5ULN.
11. Informed consent from the patient.

Exclusion Criteria:

1. Have received systemic anti-cancer therapy, including Cytotoxic drugs, targeted therapy, experimental treatment, adjuvant or neo-adjuvant therapy(except the disease relapse 6 months after the final drug)
2. Wild type EGFR.
3. Uncontrolled pericardial or pleural effusions prior to study entry.
4. History of cardiovascular disease: Congestive Heart Failure \> grade II in NYHA. Unstable angina patients (have angina symptoms in rest) or a new occurrence of angina (began in the last 3 months) or myocardial infarction happens in the last 6 months
5. Brain metastasis (controlled brain metastasis and steroid free need is excluded).
6. HIV infection
7. Active infection, \>grade 2 in Common Terminology Criteria for Adverse Events(CTCAE) version 3.
8. A history of operation or serious traumatic 3 weeks before the first drug administration
9. Patient with other malignant tumor except NSCLC 5 years previous to study entry. Excluding cervical carcinoma in situ, cured basal cell carcinoma, bladder epithelial tumor \[including Ta and Tis\]
10. Mixed with small cell lung cancer
11. Unable to swallow drugs.
12. Malabsorption
13. Pregnant or child breast feeding women
14. Childbearing patients will not use a reliable method of contraception before the study entry, during process of the study and within 30 days after discontinuation of the study. Reliable contraceptive methods will be determined by principal investigator or a designated officer.
B: 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
C: Inclusion Criteria:

* Adult participants, ≥ 18 years of age.
* Locally advanced or recurrent (stage IIIB) or metastatic (stage IV) non-small cell lung cancer.
* Presence of epidermal growth factor receptor (EGFR) mutations in tumours.
* Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria.
* European Cooperative Oncology Group (ECOG) performance status ≤ 2.

Exclusion Criteria:

* Prior exposure to agents directed at the human epidermal receptor (HER) axis (eg, but not limited to erlotinib, gefitinib, cetuximab, or trastuzumab).
* Prior chemotherapy or systemic anti-neoplastic therapy for advanced disease.
* Lack of physical integrity of the upper gastrointestinal tract, or malabsorption syndrome, or inability to take oral medication, or active gastroduodenal ulcer disease.
* Any inflammatory changes of the surface of the eye.
* ≥ Grade 2 peripheral neuropathy.
* History of any other malignancies within 5 years, except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer.
* Brain metastasis or spinal cord compression that has not yet been definitely treated with surgery and/or radiation, or treated but without evidence of stable disease for at least 2 months.
* Human immunodeficiency virus (HIV) infection.
* Pregnant, nursing, or lactating women.
D: Inclusion Criteria:

* adult patients, \>=18 years of age;
* advanced (stage IIIB/IV)non-small cell lung cancer;
* measurable disease;
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.

Exclusion Criteria:

* prior exposure to agents directed at the HER axis;
* prior chemotherapy or systemic anti-tumor therapy after advanced disease;
* unstable systemic disease;
* any other malignancy within last 5 years, except cured basal cell cancer of skin or cured cancer in situ of cervix;
* brain metastasis or spinal cord compression.

Answer: D