Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Open-label, Multi-center Phase III Study of Erlotinib Versus Gemcitabine/Carboplatin in Chemo-naive Stage IIIB/IV Non-Small Cell Lung Cancer Patients With EGFR Exon 19 or 21 Mutation (Optimal)
Brief Summary: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) such as erlotinib have proved effective in second or third line therapy for advanced non-small cell lung cancer(NSCLC).It is well tolerated without the side effects usually associated with chemotherapy. The mutations in EGFR exons 19 or 21 have been reported to be associated with efficacy of EGFR TKIs.Based on the encouraging preliminary results from the Spanish lung cancer group' prospective study reported that the efficacy of Tarceva as first line treatment for metastatic NSCLC patients with EGFR mutation would delay disease progression,prolong overall survival and be well tolerated, medium Progression-free survival(PFS) was around 12 months and OS reach 24 months，our study is designed to compare PFS between the patients with mutant EGFR treated by gemcitabine/carboplatin and those by erlotinib in the first-line setting. We assumed 11 months of PFS on Tarceva arm versus 6 months on chemotherapy arm with a=0.025(alpha-spend for an interim analysis), 80% power and 12 months enrolment period, 12 months FU duration to calculate the sample size. The sample size is 69 pairs. Considering about 10% drop-out rate, the final sample size is 152 patients.So, chemo-naive staged IIIb/IV patients with EGFR mutations in exon 19 or 21 will be enrolled into this open-label, randomized,multicenter phase III study.


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. Tumor tissue specimens from the glioblastoma surgery or open biopsy (formalin-fixed, paraffin-embedded block; stereotactic biopsy not allowed) must be available for MGMT status analysis and central pathology review
2. Newly diagnosed histologically proven supratentorial glioblastoma (World Health Organization \[WHO\] Grade IV)
3. Proven methylated MGMT gene promoter methylation status
4. Available post-operative gadolinium-enhanced magnetic resonance imaging (Gd-MRI) performed within less than (\<) 48 hours after surgery (in case it was not possible to obtain a Gd-MRI within \<48 hours post surgery, a Gd-MRI is to be performed prior to randomization)
5. Stable or decreasing dose of steroids for greater than or equal to (\>=) 5 days prior to randomization
6. Eastern Cooperative Oncology Group performance score (ECOG PS) of 0-1
7. Meets 1 of the following recursive partitioning analysis (RPA) classifications: Class III (Age \< 50 years and ECOG PS 0). Class IV (meeting one of the following criteria: a) Age \< 50 years and ECOG PS 1 or b) Age \>= 50 years, underwent prior partial or total tumor resection, mini mental state examination \[MMSE\] \>= 27). Class V (meeting one of the following criteria: a) Age \>= 50 years and underwent prior partial or total tumor resection, MMSE \< 27 or b) Age \>= 50 years and underwent prior tumor biopsy only)
8. Other protocol defined inclusion criteria could apply

Exclusion Criteria:

1. Prior chemotherapy within the last 5 years
2. Prior RTX of the head
3. Receiving concurrent investigational agents or has received an investigational agent within the past 30 days prior to the first dose of cilengitide
4. Prior systemic antiangiogenic therapy
5. Placement of Gliadel® wafer at surgery
6. Inability to undergo Gd-MRI.
7. Planned surgery for other diseases
8. History of recent peptic ulcer disease (endoscopically proven gastric ulcer, duodenal ulcer, or esophageal ulcer) within 6 months of enrollment
9. History of malignancy. Subjects with curatively treated cervical carcinoma in situ or basal cell carcinoma of the skin, or subjects who have been free of other malignancies for \>= 5 years are eligible for this study
10. History of coagulation disorder associated with bleeding or recurrent thrombotic events
11. Clinically manifest myocardial insufficiency (New York Heart Association \[NYHA\] III, IV) or history of myocardial infarction during the past 6 months; uncontrolled arterial hypertension
12. Other protocol defined exclusion criteria could apply
C: Inclusion Criteria-

Among other criteria, patients must meet the following conditions to be eligible for the study:

1. Adult patients, ≥ 18 years old
2. Newly diagnosed glioblastoma
3. Attempted surgical resection followed by conventional chemoradiation
4. Documented EGFRvIII positive tumor status by a Sponsor designated laboratory
5. No evidence of progressive disease from the post-operative period to the post-chemoradiation period
6. Candidate for, and agrees to receive, adjuvant (maintenance) temozolomide therapy
7. Systemic corticosteroid therapy at ≤2 mg of dexamethasone or equivalent per day for at least 3 days prior to randomization
8. WHO-ECOG Performance Status ≤ 2
9. Patients of childbearing/reproductive potential will be instructed to use birth control as defined by your doctor.

Exclusion Criteria-

Among other criteria, patients who meet the following conditions are NOT eligible for the study:

1. Stereotactic biopsy only (without further surgical resection)
2. Presence of diffuse leptomeningeal disease, gliomatosis cerebri, or infratentorial disease.
3. History, presence, or suspicion of metastatic disease
4. Patients who have received any additional treatment for glioblastoma, aside from surgical resection and chemoradiation with temozolomide
5. Active systemic infection requiring treatment
6. History of any malignancy (other than glioblastoma) during the last three years except non-melanoma skin cancer, in situ cervical cancer, treated superficial bladder cancer, cured, early-stage prostate cancer in a patient with PSA level less than ULN,or other carcinoma in situ that has been adequately treated and cured.
7. Planned major surgery
8. Evidence of current drug or alcohol abuse
9. Known allergy or hypersensitivity to keyhole limpet hemocyanin (KLH), GM-CSF (sargramostim; LEUKINE®), polysorbate 80 or yeast derived products, or a history of anaphylactic reactions to shellfish proteins
10. Severe acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with participating in a clinical trial
11. Women who are pregnant or lactating
D: Inclusion Criteria:

* Histologically proven diagnosis of glioblastoma or gliosarcoma (World Health Organization \[WHO\] grade IV) confirmed by central review prior to step 2 registration
* Tumor tissue that is determined by central pathology review prior to step 2 registration to be of sufficient size for analysis of O-6-methylguanine-DNA methyltransferase (MGMT) and determination of molecular profile

  * Patients must have at least 1 block of tumor tissue; submission of 2 blocks is strongly encouraged to maximize the chances of eligibility; at least 1 cubic centimeter of tissue composed primarily of tumor must be present
  * CUSA (Cavitron ultrasonic aspirator)-derived material is not allowed; fresh frozen tumor tissue acquisition is encouraged
  * Diagnosis must be made by surgical excision, either partial or complete; stereotactic biopsy is not allowed because it will not provide sufficient tissue for MGMT analysis
  * The tumor tissue should be sent as soon as possible to maximize the likelihood of eligibility; tumor tissue should be submitted by 4 weeks after the surgical procedure so that the study registration and treatment can commence by the mandatory 5 week post-surgery outer limit
  * Sites must submit tissue fir central review in order to obtain the MGMT analysis; patients from sites not following protocol-specified process for obtaining MGMT results will be made ineligible
* The tumor must have a supratentorial component
* History/physical examination within 14 days prior to step 2 registration
* The patient must have recovered from the effects of surgery, postoperative infection, and other complications before step 2 registration
* A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively and postoperatively prior to the initiation of radiotherapy; the postoperative scan must be performed within 28 days prior to step 1 registration

  * An MRI or computed tomography (CT) scan (potentially in addition to the postoperative scan) must be obtained within 10 days prior to the start of radiation therapy and must not demonstrate significant postoperative hemorrhage defined as \> 1 cm diameter of blood; if \> 1 cm of acute blood is detected, the patient will be ineligible for this trial; the radiation planning MRI or CT scan may be used to determine presence of hemorrhage
  * Patients unable to undergo MR imaging because of non-compatible devices can be enrolled, provided pre- and postoperative contrast-enhanced CT scans are obtained and are of sufficient quality; preoperative and postoperative scans must be the same type; such patients cannot be enrolled into the advanced imaging component
* Documentation of steroid doses within 14 days prior to step 2 registration
* Karnofsky performance status \>= 70
* Absolute neutrophil count (ANC) \>= 1,800 cells/mm\^3
* Platelets \>= 100,000 cells/mm\^3
* Hemoglobin \>= 10.0 g/dL (Note: the use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= 10.0 g/dl is acceptable)
* Blood urea nitrogen (BUN) =\< 30 mg/dL within 14 days prior to step 2 registration
* Creatinine =\< 1.7 mg/dl within 14 days prior to step 2 registration
* Urine protein screened by urine analysis for urine protein creatinine (UPC) ratio; for UPC ratio \> 0.5, 24-hour urine protein should be obtained and the level should be \< 1000 mg
* Bilirubin =\< 2.0 mg/dl within 14 days prior to step 2 registration
* Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =\< 3 x normal range within 14 days prior to step 2 registration
* Systolic blood pressure =\< 160 mg Hg or diastolic pressure =\< 90 mm Hg within 14 days prior to step 2 registration
* Electrocardiogram without evidence of acute cardiac ischemia within 14 days prior to step 2 registration
* Prothrombin time/international normalized ratio (PT INR) \< 1.4 for patients not on warfarin confirmed by testing within 14 days prior to step 2 registration
* Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight \[LMW\] heparin) must meet both of the following criteria:

  * No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
  * In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of LMW heparin
* Patient must provide study specific informed consent prior to study entry
* Women of childbearing potential and male participants must practice adequate contraception
* For females of child-bearing potential, negative serum pregnancy test within 14 days prior to step 2 registration

Exclusion Criteria:

* Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for \>= 3 years; (for example, carcinoma in situ of the breast, oral cavity, and cervix are all permissible)
* Recurrent or multifocal malignant gliomas
* Metastases detected below the tentorium or beyond the cranial vault
* Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note that prior chemotherapy for a different cancer is allowable, except prior temozolomide or bevacizumab; prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted
* Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields
* Severe, active co-morbidity, defined as follows:

  * Unstable angina and/or congestive heart failure within the last 6 months
  * Transmural myocardial infarction within the last 6 months
  * Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of \>= 2 mm using the analysis of an electrocardiogram (EKG) performed within 14 days of step 2 registration
  * New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to step 2 registration
  * History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months
  * Serious and inadequately controlled cardiac arrhythmia
  * Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease
  * Evidence of bleeding diathesis or coagulopathy
  * Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to step 2 registration, with the exception of the craniotomy for tumor resection
  * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 2 registration
  * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol
  * Acquired immune deficiency syndrome (AIDS) based upon current Center for Disease Control (CDC) definition; note, however, that HIV testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive
  * Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity
  * Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy
* Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
* Pregnant or lactating women
* Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study
* For American College of Radiology Imaging Network (ACRIN) 6686 Advanced Imaging: inability to undergo MRI (e.g., due to safety reasons, such as presence of a pacemaker)

Answer: A