Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Open Label Multicenter Phase II Study of First Line Therapy With Sorafenib in Association With IL-2 vs Sorafenib Alone in Patients With Unresectable and/or Metastatic Renal Cell Carcinoma
Brief Summary: The ROSORC trial is a randomized study comparing the efficacy of a new association (sorafenib and IL-2) versus the standard therapy (sorafenib) in patients affected by different histotypes of metastatic RCC. This study is a first line therapy for the advanced disease. The primary objective is the progression free survival (PFS) in the 2 arms of therapy and the secondary objective is the overall survival (OS) and the response rate (RR) and the safety profile of the combination compared to sorafenib alone.


Options:
A: Inclusion Criteria:

* Age: 20-80 years old, both inclusive
* ECOG performance status of 0, 1, or 2
* MSKCC risk of favorable or intermediate
* Histologically confirmed renal cell carcinoma
* No ischemic heart disease
* Laboratory findings meet the following criteria:

  1. Respiratory function: %VC, 80% and FEV1.0,70%
  2. Hematology: white blood cell count4,000/mm3, platelet count100,000/mm3
  3. Clinical chemistry: GOT and GPT within the normal range of each medical institution; total bilirubin \<1.5 x ULN
  4. Serum creatinin \<2.0mg/dl, blood urea nitrogen (BUN) \<25mg/dl
  5. Echocardiographic estimation of left ventricular ejection fraction is higher than the lower limit of reference range of each medical institution.

Exclusion Criteria:

* History of any other malignancy
* Central nervous system metastases. However, patients who remain asymptomatic, have no new or enlarging lesion in the CNS within 6 months of enrollment in this study, and require no corticosteroids may be enrolled.
* History of cardiac infarction, unstable angina, congestive heart failure, or symptomatic peripheral vascular disease within 12 months of enrollment
* History of cerebrovascular disorder including transient ischemic attack (TIA)
* Pregnancy or possible pregnancy at any time during the study
* Ongoing grade 2 adverse event prior treatment
* Prior treatment with any anticancer therapy including cytokine therapy such as interferon-alpha and interleukin-2
* Prior treatment with mTOR inhibitor
* Prior treatment with sunitinib or sorafenib
* Treatment with an test drug in a clinical research within 4 weeks of enrollment in this study
B: Inclusion Criteria:

* Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow-up.
* Age ≥ 18 years.
* Histologically confirmed diagnosis of progressive metastatic clear cell renal cell cancer defined as \>10% of the tumor cells having the clear cell phenotype.
* Locally advanced (defined as disease not amenable to curative surgery or radiation therapy) or metastatic RCC (equivalent to Stage IV RCC according to AJCC staging).
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
* Measurable disease.
* No prior systemic anti-cancer treatment against clear cell renal carcinoma.
* Adequate organ system function.
* Non-childbearing potential.

Exclusion Criteria:

* Prior malignancy.
* History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis.
* Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding.
* Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product.
* Presence of uncontrolled infection.
* Known past or present infection with Hepatitis B virus (HBV), Hepatitis C virus (HCV) or Human Immunodeficiency Virus (HIV).
* Corrected QT interval (QTc) \> 480 msecs using Bazett's formula.
* History of one or more of the following cardiovascular conditions within the past 6 months:

  1. Cardiac angioplasty or stenting
  2. Myocardial infarction
  3. Stable or unstable angina pectoris.
  4. Coronary artery bypass graft surgery.
  5. Symptomatic peripheral vascular disease
  6. Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA).
* Poorly controlled hypertension \[defined as systolic blood pressure (SBP) of ≥160 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg\].
* History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
* Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any nonhealing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major).
* Evidence of active bleeding or bleeding diathesis.
* Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels.
* Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks of first dose of study drug.
* Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
* Unable or unwilling to discontinue use of prohibited medications or modify the dosing of interacting drugs for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study.
* Pregnant or lactating female.
* Treatment with any of the following anti-cancer therapies: Radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of Pazopanib OR Chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy.
C: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

* Subjects with histological confirmation of RCC
* Advanced or metastatic disease
* Measurable disease as defined by RECIST 1.1 criteria
* Karnofsky Performance Status (KPS) ≥80%
* Available tumor tissue (archival or recent acquisition)
* Subjects enrolled in the I-1, I-3 expansion arms and IN-3 addition arms must not have received any prior systemic therapy for RCC with the following exceptions:

  1. One prior adjuvant or neoadjuvant therapy for localized or locally advanced RCC is allowed provided recurrence occurred ≥ 6 months after the last dose of the adjuvant or neoadjuvant therapy
  2. Only prior cytokine based treatment for metastatic RCC \[eg, interferon-alpha (IFN-alpha) or interleukin 2 (IL-2)\] as prior therapy is allowed

Exclusion Criteria:

* Active central nervous system (CNS) metastases
* Active or history of autoimmune disease
* Ongoing symptomatic cardiac dysrhythmias or uncontrolled atrial fibrillation
* History of cerebrovascular accident including transient ischemic attack within the past 12 months
* History of pulmonary embolism or deep vein thrombosis (DVT) within the past 6 months
* Chronic systemic steroids (\>10 mg/day Prednisone equivalents) or any other immunosuppressive agents
* White blood cell (WBC) \<2,000/mm3
* Neutrophiles \<1,500/mm3
* Platelets \<100,000/mm3
* Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) \>3x upper limit of normal (ULN)
* Total Bilirubin \>1.5x ULN (except subjects with Gilbert syndrome, total bilirubin \<3.0 mg/dL)
* Cardiac ejection fraction \<LLN (lower limit of normal)
* Serum creatinine \>1.5x ULN or creatinine clearance \<40 mL/min (Cockroft-Gault formula)

Exclusion Criteria for Arm S and Arm P only:

* For dose escalation cohorts - subjects who received prior Sunitinib or Pazopanib and required permanent discontinuation due to toxicity or required dose reduction or delay during the first 12 weeks of therapy due to toxicity, or received both prior Sunitinib and Pazopanib
* Poorly controlled hypertension
* Active bleeding or bleeding susceptibility
D: Inclusion Criteria:

* Cytohistological diagnosis of RCC
* Written informed consent
* Measurable disease according to RECIST criteria
* Age \>= 18 years
* Karnofsky PS \>= 60%
* Life expectancy of greater than 3 months

Exclusion Criteria:

* Prior medical treatment for metastatic RCC
* Brain metastasis or spinal cord compression
* Chronic treatment with corticosteroids
* Uncontrolled hypertension

Answer: D