Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double Blinded, Multi-Center Phase 2 Study to Estimate the Efficacy and Evaluate the Safety and Tolerability of Sorafenib in Combination With AMG 386 or Placebo In Subjects With Metastatic Clear Cell Carcinoma of the Kidney
Brief Summary: This is a phase 2, randomized, double-blind, placebo controlled, multi-center study to estimate the improvement in progression free survival (PFS) and evaluate the safety and tolerability of AMG 386 in combination with sorafenib in the treatment of subjects with advanced clear cell carcinoma of the kidney.


Options:
A: Pre-Surgery Inclusion Criteria:

* Primary-intact resectable renal cell cancer, without known distant metastasis and be scheduled to have surgery with curative intent;
* Tumor size greater than or equal to 5 cm OR macroscopic nodes OR renal vein thrombus OR vena cava thrombus by radiologic evaluation
* Performance status (Zubrod / ECOG-WHO scale)less than or equal to 1 and life expectancy of greater than three months, within 2 weeks of surgery.
* Women of child-bearing potential must have a negative urine or serum pregnancy test within 2 weeks of surgery.
* Signed written informed consent.

Pre-Surgery Exclusion Criteria:

* Prior chemo-, hormonal, immuno- or radiotherapy for renal cell cancer;
* History of primary or secondary immunodeficiency, or patients using immunosuppressive drugs, e.g. systemic corticosteroids, cyclosporin A;
* Current malignancies at other sites or previous other cancer within the last 5 years, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri or basal or squamous cell carcinoma of the skin;
* Embolization of the renal artery prior to nephrectomy;
* Known distant metastases;
* Active, uncontrolled infection or other serious medical illnesses.

Eligibility Assessment:

(between 2 weeks pre- and 4 weeks post-surgery)

Prior to randomization and entry into the tumor evaluation phase, all subjects must undergo testing to confirm that they are free of distant metastatic disease, and that they meet all other criteria.

Eligibility Criteria which must be assessed and confirmed prior to randomization:

* No evidence of metastatic or residual renal carcinoma as documented by all of the following: abdominal/pelvis CT scan; chest CT scan; and brain CT or MRI scan.
* Provide Antigenics with greater than or equal to 7 grams of viable tumor tissue
* Adequate bone marrow function.
* Adequate renal and hepatic function.
* Adequate cardiac function.
* Signed written informed consent.
* Patients must be willing to be followed during the course of tumor evaluation and follow-up phases.
* Male or female patients of child producing potential must agree to use adequate contraception during the treatment/observation phase of the study.
* Patients must not use any other investigational drug for four weeks prior to the start of the tumor evaluation phase and throughout the tumor evaluation phase of the study.
B: Inclusion Criteria:

* Subjects must have a histologically confirmed metastatic RCC with a clear cell component
* Low or intermediate risk according to the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk classification.
* Measurable disease with at least one unidimensionally measurable lesion per RECIST guidelines with modifications
* Adequate organ and hematological function as evidenced by laboratory studies conducted at Screening.
* ECOG of 0 or 1

Exclusion Criteria:

Disease Related

* Known history of central nervous system metastases.
* Previous treatment (excluding surgery and palliative radiotherapy) for advanced or metastatic renal cell carcinoma
* Focal radiation therapy for palliation of pain from bony metastases within 14 days of randomization.

Medications

* Currently or previously treated with inhibitors of VEGF.
* Currently or previously treated with inhibitors of angiopoietin or Tie2.
* Currently or previously treated with bevacizumab.

General Medical

* Diagnosis of acute pancreatitis.
* Myocardial infarction, cerebrovascular accident, transient ischemic attack, percutaneous transluminal coronary angioplasty/stent, congestive heart failure, grade 2 or greater peripheral vascular disease, arrhythmias not controlled by outpatient medication, or unstable angina within 1 year prior to randomization
* Major surgery within 30 days before randomization or still recovering from prior surgery
* Uncontrolled hypertension as defined as diastolic \> 90 mmHg OR systolic \>150 mmHg. Anti-hypertensive medications are permitted.

Other

* Other investigational procedures are excluded
* Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s), or subject is receiving other investigational agent(s)
C: Inclusion Criteria:

1. Aged at least 18 years.
2. HLA type: HLA-A\*02-positive
3. Metastatic and/or locally advanced RCC with clear cell histology (histological confirmation by local pathologist required). NOTE: prior nephrectomy is NOT required.
4. Measurable and/or non-measurable tumor lesions as per RECIST 1.1
5. Patients who are candidates for a first-line therapy with sunitinib.
6. Favorable or intermediate risk according to the 6-score risk criteria in patients treated with VEGF-targeted agents according to Heng \[Heng et al. 2009\]. The patient has a favorable risk if none, or intermediate risk if one or two of the following criteria apply (if three or more criteria apply the patient is not eligible):

   1. Hemoglobin \< LLN,
   2. Serum corrected calcium \> ULN,
   3. Karnofsky performance status \< 80%,
   4. Time from initial diagnosis to initiation of therapy \< 1 year,
   5. Absolute neutrophil count \> ULN,
   6. Platelets \> ULN.
7. Able to understand the nature of the study and give written informed consent.
8. Willingness and ability to comply with the study protocol for the duration of the study.
9. Female patients who are post menopausal (no menstrual period for a minimum of 1 year), or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) or practice a medically acceptable method of birth control.
10. Male patients willing to use contraception (upon study entry and during the course of the study or have undergone vasectomy.

Exclusion Criteria:

1. Prior systemic therapy for metastatic disease. (Note: prior adjuvant treatment for non-metastatic disease is allowed, however adjuvant therapy must have been stopped ≥ 1 year before Visit C).
2. History of or current brain metastases.
3. Abnormal ≥ CTC Grade 3 laboratory values for hematology (Hb, WBC, neutrophils, lymphocytes, platelets), liver (serum bilirubin, ALAT or ASAT) and renal function (serum creatinine).
4. Metastatic second malignancy.
5. Localized second malignancy expected to influence the patient's life span.
6. Patients with a history or evidence of systemic autoimmune disease, e.g., rheumatoid arthritis, multiple sclerosis, systemic lupus erythematodes (SLE), scleroderma, Sjögren's syndrome, Wegener's granulomatosis, Guillain-Barre syndrome.
7. Known active hepatitis B or C infection.
8. Known HIV infection.
9. Active infections requiring oral or intravenous antibiotics.
10. Any other known infection with a biological agent that can cause a severe disease and poses a severe danger to lab personnel working on patients' blood or tissue.
11. Received study drug within any clinical study (including approved and experimental drugs) within 4 weeks before sunitinib start.
12. Serious intercurrent illness, which according to the investigator, poses an undue risk for the patient when participating in the trial, including, but not limited to, any of the following:

    * Clinically significant cardiovascular disease (e.g., uncontrolled hypertension; clinically significant cardiac arrhythmia, clinically significant QT-prolongation),
    * New York Heart Association class III-IV congestive heart failure,
    * Symptomatic peripheral vascular disease,
    * Severe pulmonary dysfunction,
    * Psychiatric illness or social situation that would preclude study compliance.
13. Less than 12 months since any of the following:

    * Myocardial infarction,
    * Severe or unstable angina,
    * Coronary or peripheral artery bypass graft,
    * Cerebrovascular event incl. transient ischemic attack,
    * Pulmonary embolism / deep vein thrombosis (DVT).
14. Pregnancy or breastfeeding.
15. Any condition which in the judgment of the investigator would place the patient at undue risk or interfere with the results of the study.
D: Inclusion Criteria:

* This study will be conducted in subjects with histologically confirmed, advanced (stage IV or recurrent disease) RCC who have not received prior systemic therapy for their disease,

Exclusion Criteria:

* Subjects with central nervous system (CNS) metastases
* Prior anticancer therapy for RCC
* Prior investigational therapy/agents within 4 weeks of randomization

Answer: B