Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Placebo-Controlled, Multicentre, Randomised, Parallel Group, Trial to Assess the Efficacy, Safety and Tolerability of Gefitinib (Iressa® 250mg) as Maintenance Therapy in Locally Advanced or Metastatic (StageIIIB/IV) Non Small Cell Lung Cancer (NSCLC) Chinese Patients Who HaveNot Experienced Disease Progression or Unacceptable Toxicity During Front Line Standard Platinum-Based Chemotherapy
Brief Summary: This is a double blind, multicentre, randomized, placebo-controlled study. The eligible patients will be randomized to receive gefitinib or placebo at 1:1 ratio. This study will recruit 296 male or female, histologically or cytologically diagnosed locally advanced or metastatic NSCLC patients with a World Health Organization (WHO) Performance Status (PS) 0-2. Patients must have completed 4 cycles of platinum based first line doublet chemotherapy without experiencing disease progression or unacceptable toxicity. The chemotherapy shall be given every 3 weeks, which includes cisplatin or carboplatin, combined with any one of the following: gemcitabine, paclitaxel, docetaxel, vinorelbine.


Options:
A: Inclusion Criteria:

* More than 18 years of age
* Histologically documented non-small cell lung cancer with metastasis (Stage IV) or locally advanced (Stage IIIB) with malignant effusion.
* At least 1 measurable lesion as defined by RECIST1.0. All target lesions must have a unidirectional diameter of at least 1cm. Baseline measurements must be compared within 4 weeks prior to enrollment.
* ECOG PS 0-2
* At least 1 week since the last radiotherapy. Patients must have recovered from all acute toxicities from radiotherapy.
* Patients must have adequate hematologic, renal and liver function as defined by Hb \> 9g/dL, neutrophils \> 1000/mm3, platelets \> 50,000/mm3, creatinine \< 2mg/dL, and AST (SGOT) and/or ALT (SGPT) \< 5 x UNL (upper normal limit).
* Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.
* Written and voluntary informed consent understood, signed and dated.

Exclusion Criteria:

* Patients with tumor harboring EGFR mutation.
* Prior systemic therapy for NSCLC
* Non-smoking patients with adenocarcinoma. But if those patients show wild type EGFR, they are eligible to this study.
* Symptomatic brain metastasis. Brain metastases stable \< 2 weeks before dosing or requiring concurrent steroid treatment or with clinical symptoms.
* Major surgery within 3 weeks prior to study enrollment.
* Previous (less than 3 years ago) or current malignancies at sites other than curatively treated in situ carcinoma of cervix, or basal or squamous cell carcinoma of the skin.
* Severe medical illness or active infection that would impair the ability to receive gefitinib.
* Pregnancy or breast feeding.
B: Inclusion Criteria:

* Histologically or cytologically confirmed locally advanced or metastatic (stage=IIIB/IV) non-small cell lung cancer (NSCLC) before the front line chemotherapy. Note: sputum cytology alone is not acceptable
* Patients have completed 4 cycles of first line platinum contained doublet chemotherapy without progression or intolerable toxicity.
* Patients with PR or SD on study entry need to have one or more measurable lesions according to RECIST criteria.
* The study treatment should be started at least 3 weeks (21 days) but no more than 6 weeks (42 days) since last dose of chemotherapy, and within 4 weeks (28 days) since last tumour assessment.

Exclusion Criteria:

* Prior exposure to monoclonal antibodies or small molecule inhibitors against EGFR receptors. (e.g. gefitinib, erlotinib, C225)
* Patients with previously diagnosed and treated CNS metastases or spinal cord compression may be considered if they are clinically stable and have been discontinued from steroid therapy for at least 4 weeks prior to first dose of study medication.
* Any evidence of clinically active interstitial lung disease (patients with chronic, stable, radiographic changes who are asymptomatic need not be excluded)
* Known biomarker status of one or more of the following: Tumour EGFR gene copy number, tumour EGFR gene mutation status, tumour EGFR protein expression.
C: Inclusion Criteria:

1. Confirmed NSCLC with Histology or cytology; advanced （IIIb/IV).
2. Must have received 1 or 2 chemotherapy (at least 1 is platin based)before, and prior chemotherapy must be completed at least 4 weeks before study enrollment; =.

Exclusion Criteria:

1. Previous usage of EGFR-TKI or antibody to EGFR: gefitinib, erlotinib, herceptin, erbitux.
D: Inclusion Criteria:

1. Informed consent must be signed.
2. At least 18 years of age.
3. Histologic or cytologic diagnosis of NSCLC.
4. Locally advanced or metastatic disease (stage IIIB, or IV) that is not amenable to definitive surgery or radiotherapy.
5. Patients must have previously received one platinum-based chemotherapy regimen for palliative therapy of locally advanced or metastatic disease. Patients are also eligible if they have received one platinum-based chemotherapy regimen as neoadjuvant or adjuvant chemotherapy and the disease recurred within six months since the finishing of neoadjuvant or adjuvant chemotherapy.
6. Without EGFR mutations.
7. At least one measurable lesion as defined by RECIST criteria.
8. ECOG PS0 - 2.
9. Adequate organ function including the following:

   * bone marrow;
   * hepatic;
   * renal.
10. Prior chemotherapy must be completed at least 3 weeks prior to the study enrollment, and the patient must have recovered from the toxic effects of the treatment (except for alopecia).
11. Previous palliative radiation therapy is allowed, but limited in LESS 25% of the bone marrow and must not have included whole pelvis radiation. Patients must have recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia). Prior radiotherapy must be completed one month before study entry. Radiotherapy should not be administered to target lesions selected for this study, unless progression of the selected target lesions within the radiation portal is documented.
12. Estimated life expectancy of at least 8 weeks.
13. For women:

    * must be surgically sterile;
    * postmenopausal; OR
    * compliant with a medically approved contraceptive regimen during and for 3 months after the treatment period; must have negative serum or urine pregnancy test and must not be lactating.
14. For men:

    * must be surgically sterile; OR
    * compliant with a contraceptive regimen during and for 3 months after the treatment period.
15. Patient compliance and geographic proximity that allow adequate follow-up.

Exclusion Criteria:

1. Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry or concurrent administration of any other anti-tumor therapy.
2. Have previously participated in a study involving pemetrexed or EGFR-TKI
3. Hypersensitivity to pemetrexed or gefitinib or any ingredients in the two drugs.
4. Symptomatic central nervous system (CNS) metastases and asymptomatic CNS metastases requiring concurrent corticosteroid therapy. Treated stable CNS metastases are allowed; the patient must be stable after radiotherapy for more than 2 weeks and off of corticosteroids for more than 1 week. .
5. History of another malignancy within the last 5 years except cured carcinoma in-situ of uterine cervix, cured basal cell carcinoma of skin and superficial bladder tumors (Ta, Tis and T1)
6. Lack of physical integrity of the upper gastrointestinal tract, or malabsorption syndrome, or inability to take oral medication, or have active peptic ulcer disease.
7. Patients with interstitial lung disease.
8. Any unstable systemic disease (including active infection, hepatic, renal or metabolic disease) or serious concomitant disorders that would compromise the safety of the patient, or compromise the patient's ability to complete the study, at the discretion of the investigator.
9. Significant cardiovascular event: congestive heart failure \>NYHA class 2; unstable angina, active CAD (myocardial infarction more than 1 year prior to study entry is allowed); serious cardiac arrhythmia requiring antiarrythmic therapy ( beta blockers or digoxin are permitted) or uncontrolled hypertension.
10. History of significant neurological or mental disorder, including seizures or dementia.
11. Incision from operation has not healed before the start of study treatment (Small incision for biopsy is eligible.)
12. Pregnant or breast-feeding women and childbearing potential women with either a positive or no pregnancy test within 48 hours of the start of treatment. Postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of non-childbearing potential.
13. Concurrent use of St. John's Wort, Rifampicin, and/or ritonavir.
14. Inability to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) 2 days before, the day of, and 2 days after the dose of pemetrexed. If a patient is taking an NSAID (Cox-2 inhibitors included) or salicylate with a long half-life (e.g., naproxen, piroxicam, diflunisal, nabumetone, rofecoxib, or celecoxib) it should not be taken 5 days before, the day of, and 2 days after the dose of pemetrexed.
15. Presence of clinically detectable (by physical exam) third-space fluid collections, for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study entry.
16. Inability or unwillingness to take folic acid, vitamin B12 supplementation, or dexamethasone.

Answer: B