Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Open-label, Randomized, Multi-center, Phase III Study to Compare the Safety and Efficacy of Dovitinib Versus Sorafenib in Patients With Metastatic Renal Cell Carcinoma After Failure of Anti-angiogenic (VEGF-targeted and mTOR Inhibitor) Therapies
Brief Summary: This study will evaluate the safety and efficacy of Dovitinib versus sorafenib in patients with metastatic renal cell cancer.


Options:
A: Inclusion Criteria:

* Male or female patients\>= 18 years of age;
* Patients with histological or cytological evidence of metastatic renal cell carcinoma mostly of all type,except for papillary;
* No prior systemic treatment (chemotherapy, immunotherapy, anti-angiogenic drugs, or treatment under evaluation) for metastatic renal cancer;
* No brain metastases revealed by MRI or CT-scan within 28 days prior to randomization. Patients with a history of brain metastases treated by surgery +/- radiation therapy can be included if they have normal brain MRI;
* E.C.O.G performance status =\<2;
* At least one measurable lesion using the RECIST criteria;
* Blood tests and renal and liver functions in the normal range with, in the 7 days prior to study entry, blood or serum values as follows:

Hemoglobin \> 8g/dl; Neutrophil count \> 1500\*10exp9/L; Platelets \> 100\*10exp9/L; Serum creatinine \< 200µmol/L; Total Bilirubin \< 1.5 times upper limit of normal; ALT and AST \< 2.5 times upper limit of normal or \< 5 ULN for patients with liver metastases, PT or INR \< 1.5 times upper limit of normal in the absence of anticoagulant therapy;

* Absence of proteinuria confirmed by urinary dipstick test
* Fertile women must use effective means of contraception
* Mandatory affiliation with a healthy security insurance
* Signed written informed consent.

Exclusion Criteria:

* Patient with pure papillary renal cell carcinoma
* Prior systemic treatment for metastatic renal cancer
* History of other malignancies, other than curatively treated in-situ carcinoma of the cervix or basal cell carcinoma of the skin, or any other curatively treated cancer with no sign of recurrence within 5 years prior to randomization
* Evidence of brain metastasis by computerized tomographic scan or MRI in the 28 days prior to randomization. Patients with history of brain metastases treated by exclusive brain therapy are not allowed to participate, even if brain MRI is normal
* Significant cardiovascular disease or uncontrolled hypertension while receiving appropriate medication (\>= 160 mm Hg systolic and/or \>= 90 mm Hg diastolic)
* Hepatic affection like chronic advanced hepatitis, liver cirrhosis or chronic hepatitis recently treated or in process of treatment by immunosuppressive agents, hepatitis auto-immune or history of auto-immune disease
* Major surgical procedure, open biopsy, or serious non healing wound within 28 days prior to randomization
* Uncontrolled hypercalcemia while receiving appropriate treatment
* Uncontrolled hypercholesterolemia or hypertriglyceridemia
* Patient under anti-vitamin K therapy
* Patient under strong CYP3A4 inhibitors
* Patient with severe neuropsychiatric disorder (or comitial crises)
* Patient included in another clinical trial, except for supportive care trials
* Pregnant or lactating women (mandatory negative serum or urinary pregnancy test at study entry for all women of childbearing potential)
B: Inclusion Criteria:

* Patients with metastatic carcinoma and with histological or cytological confirmation of clear cell RCC (tissue from the original diagnosis of renal cell cancer is acceptable).
* The date of progression on sunitinib and/or sorafenib must be within 6 months.
* Patients may have received one or both agents
* Prior therapy with cytokines (i.e., IL-2, Interferon) and/or VEGF-ligand inhibitors (i.e., bevacizumab) are permitted.
* Prior vaccine therapy in the adjuvant setting is permitted.
* Patients with at least one measurable lesion at baseline as per the Response evaluation criteria in solid tumors (RECIST) criteria, either on physical exam or as determined by Computer Tomography (CT) Scan or Magnetic Resonance Imaging (MRI).
* Patients with a Karnofsky Performance Status ≥70%.
* Adequate bone marrow, liver and renal function.
* Patients with a life expectancy ≥ 3 months.
* Women of childbearing potential must have had a negative serum or urine pregnancy test 48 hours prior to the administration of the first study treatment.
* Patients who give a written informed consent obtained according to local guidelines

Exclusion Criteria:

* Patients currently receiving chemotherapy, immunotherapy, or radio-therapy or who have received these within 4 weeks of study entry
* Patients who have previously received mTOR inhibitors.
* Patients with a known hypersensitivity to RAD001 or other rapamycins (sirolimus, temsirolimus) or to its excipients.
* Patients with untreated CNS metastases or who are neurologically unstable despite treatment of the CNS metastases. (Patients with treated CNS metastases, who are neurologically stable off of corticosteroids, are eligible to enter study).
* Patients receiving chronic treatment with corticosteroids or another immunosuppressive agent
* Patients with a known history of HIV seropositivity.
* Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumadin)
* Patients who have any severe and/or uncontrolled medical conditions
* Patients who have a history of another primary malignancy ≤ 3 years, with the exception of non-melanoma skin cancer, and carcinoma in situ of uterine cervix
* Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes.
* Patients who are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to randomization
* Patients unwilling to or unable to comply with the protocol

Other protocol-defined inclusion/exclusion criteria may apply.
C: Inclusion Criteria:

* Written informed consent
* Diagnosis of renal cell carcinoma with clear-cell component histology.
* Received no prior systemic therapy (interleukin-2, interferon-alpha, chemotherapy, bevacizumab, mTOR inhibitor, sunitinib, sorafenib or other VEGF TKI) for advanced or metastatic RCC
* Locally advanced or metastatic renal cell carcinoma
* Measurable disease by CT or MRI
* Karnofsky performance scale status of \>=70
* Age \>=18 years
* A female is eligible to enter and participate in this study if she is of: non-childbearing or agrees to use adequate contraception.
* Adequate organ system function
* Total serum calcium concentration \<12.0mg/dL
* Left ventricular ejection fraction \>= lower limit of institutional normal.

Exclusion Criteria:

* Pregnant or lactating female (unless agrees to refrain from nursing throughout the treatment period and for 14 days following the last dose of study)
* History of another malignancy (unless have been disease-free for 3 years)
* History or clinical evidence of central nervous system (CNS) metastases (unless have previously-treated CNS metastases and meet all 3 of the following criteria are: are asymptomatic, have had no evidence of active CNS metastases for \>=6 months prior to enrolment, and have no requirement for steroids or enzyme-inducing anticonvulsants)
* Clinically significant gastrointestinal abnormalities including, but not limited to: malabsorption syndrome, major resection of the stomach or small bowel that could affect the absorption of study drug, active peptic ulcer disease, known intraluminal metastatic lesion/s with suspected bleeding, Inflammatory bowel disease, ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation, history of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
* Presence of uncontrolled infection.
* Prolongation of corrected QT interval (QTc) \> 480 milliseconds
* History of any one or more of the following cardiovascular conditions within the past 12 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery by-pass graft surgery, symptomatic peripheral vascular disease, Class III or IV congestive heart failure, as defined by the New York Heart Association
* History of cerebrovascular accident including transient ischemic attack within the past 12 months
* History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months (unless had recent DVT and have been treated with therapeutic anti-coagulating agents for at least 6 weeks)
* Poorly controlled hypertension (defined as systolic blood pressure of \>=150mmHg or diastolic blood pressure of \>=90mmHg). Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry
* Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer.
* Evidence of active bleeding or bleeding susceptibility
* Spitting/coughing up blood within 6 weeks of first dose of study drug
* Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
* Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with patient's safety, obtaining informed consent or compliance to the study.
* Use any prohibited medications within 14 days of the first dose of study medication.
* Use of an investigational agent, including an investigational anti-cancer agent, within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study drug.
* Prior use of an investigational or licensed drug that targets VEGF or VEGF receptors (eg. bevacizumab, sunitinib, sorafenib, etc), or are mTOR inhibitors (eg. temsirolimus, everolimus, etc).
* Is now undergoing and/or has undergone in the 14 days immediately prior to first dose of study drug, any cancer therapy (surgery, tumor embolization, chemotherapy, radiation therapy, immunotherapy, biological therapy, or hormonal therapy)
* Any ongoing toxicity from prior anti-cancer therapy that is \>Grade 1 and/or that is progressing in severity.
* Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or sunitinib.
D: Inclusion Criteria:

* Patients with metastatic renal cell carcinoma (mRCC) with histological or cytological confirmation of clear cell carcinoma or a component of clear cell
* Patients must have received one and only one prior VEGF-targeted therapy and one and only one prior mTOR inhibitor therapy in the metastatic setting. One VEGF targeted therapy (e.g. sunitinib, or pazopanib, or axitinib, or tivozanib or bevacizumab) and one prior mTOR inhibitor therapy (everolimus, or temsirolimus or ridaforolimus)
* Prior cytokines therapy and prior vaccines in the adjuvant setting is permitted.
* Patients must have had disease progression on or within 6 months of stopping the last therapy.
* Patients must have at least one measurable lesion at baseline (by RECIST Criteria Guidelines v1.1) assessed by Computer Tomography (CT) Scan or Magnetic Resonance Imaging (MRI).
* Karnofsky performance status ≥ 70%
* Patients must have the following laboratory values:

  * Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
  * Platelets ≥ 100 x 109/L
  * Hemoglobin (Hgb) \> 9 g/dL
  * Serum total bilirubin: ≤ 1.5 x ULN
  * ALT and AST ≤ 3.0 x ULN (Patients with known liver metastases: AST and ALT ≤ 5.0 x ULN)
  * Serum creatinine ≤ 1.5 x ULN

Exclusion Criteria:

* Patients who have previously received sorafenib therapy in the neoadjuvant, adjuvant or metastatic setting.
* Patients who have previously received Dovitinib or brivanib in the neoadjuvant, adjuvant or metastatic setting.
* Patients with brain metastases. Radiological imaging (e.g. CT or MRI scan) of the brain is required at screening/baseline
* Patients with another primary malignancy within 3 years prior to starting study treatment, with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma or non-melanomatous skin cancer, or in-situ carcinoma of the uterine cervix
* Patients who have received the last administration of an anticancer targeted small molecule therapy ≤ 2 weeks prior to starting study treatment (e.g. sunitinib, pazopanib, axitinib, everolimus, temsirolimus), or who have not recovered from the side effects of such therapy
* Patients who have received the last administration of nitrosurea or mitomycin-C ≤ 6 weeks prior to starting study treatment, or who have not recovered from the side effects of such therapy
* Patients who have undergone major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) ≤ 4 weeks prior to starting study treatment or who have not recovered from side effects of such therapy
* Patients with a history of pulmonary embolism (PE), or untreated deep venous thrombosis (DVT) within the past 6 months
* Patients with concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study

Other protocol-defined inclusion/exclusion criteria may apply

Answer: D