Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Open-label, Multi-center Phase II Study to Compare Bevacizumab Plus RAD001 Versus Interferon Alfa-2a Plus Bevacizumab for the First-line Treatment of Patients With Metastatic Clear Cell Carcinoma of the Kidney
Brief Summary: To estimate the difference in efficacy and safety of bevacizumab and RAD001 compared to bevacizumab and interferon alfa-2a for first-line treatment of patients with metastatic carcinoma of the kidney.


Options:
A: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

* Histological confirmation of renal cell carcinoma (RCC) with a clear-cell component
* Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) RCC
* No prior systemic therapy for RCC with the following exception:

  1. One prior adjuvant or neoadjuvant therapy for completely resectable RCC if such therapy did not include an agent that targets vascular endothelial growth factor (VEGF) or VEGF receptors and if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy

     * Karnofsky Performance Status (KPS) of at least 70%
     * Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
     * Tumor tissue \[formalin-fixed paraffin-embedded (FFPE) archival or recent acquisition\] must be received by the central vendor (block or unstained slides) in order to randomize a subject to study treatment. (Note: Fine Needle Aspiration \[FNA\] and bone metastases samples are not acceptable for submission)

Exclusion Criteria:

* Any history of or current central nervous system (CNS) metastases. Baseline imaging of the brain is required within 28 days prior to randomization
* Prior systemic treatment with VEGF or VEGF receptor targeted therapy (including, but not limited to, Sunitinib, Pazopanib, Axitinib, Tivozanib, and Bevacizumab)
* Prior treatment with an anti-programmed death (PD)-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
* Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (\>10 mg daily Prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll
* Any condition requiring systemic treatment with corticosteroids (\>10 mg daily Prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses \>10 mg daily Prednisone equivalents are permitted in the absence of active autoimmune disease
B: Inclusion Criteria:

* Patients with histologically or cytologically confirmed metastatic clear cell RCC
* Patients must have measurable disease, defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) and measures \>= 20 mm with conventional techniques or \>= 10 mm with spiral CT scan
* ECOG performance status =\< 1
* Absolute neutrophil count \>= 1,500/μL
* Platelets \>= 100,000/μL
* Hgb \> 9.0 g/dL (may be transfused or receive epoetin alfa \[e.g., Epogen®\] to maintain or exceed this level)
* Total bilirubin =\< 2.0 mg/dl
* Albumin \> 3.0 g/dL
* Serum creatinine =\< 2.0 mg/dl
* AST(SGOT) and/or ALT (SGPT) =\< 2.5 X institutional upper limit of normal for subjects without evidence of liver metastases
* AST(SGOT) and/or ALT (SGPT) =\< 5 X institutional upper limit of normal for subjects with documented liver metastases
* Female patients of childbearing potential must have a normal plasma beta human chorionic gonadotropin (βHCG) within 24 hours prior to enrolling in the study due to the possible teratogenic effect; however, patients will be eligible if their βHCG elevation is consistent with malignancy rather than pregnancy
* Patients of child fathering or childbearing potential must agree to practice a form of medically acceptable birth control while on study
* Patients must give written informed consent prior to initiation of therapy, in keeping with the policies of the institution; patients with a history of major psychiatric illness must be judged able to fully understand the investigational nature of the study and the risks associated with the therapy; the only approved consent is attached to this protocol
* Patients must have ability to comply with study and/or follow-up procedures
* Patients must be able to swallow pills

Exclusion Criteria:

* No prior malignancy is allowed, except for non-melanoma skin cancer, in situ carcinoma of any site, or other cancers for which the patient has been adequately treated and disease free for 5 years
* Patients must not have received any systemic anticancer therapy for renal cell carcinoma; patients must not have received any radiotherapy for renal cell carcinoma within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
* Patients must not be scheduled to receive another experimental drug while on this study; patients are permitted to be on concomitant bisphosphonates
* Patients must not have a primary brain tumor, any brain metastases, leptomeningeal disease, seizure disorders not controlled with standard medical therapy, or history of stroke
* Patients must not have active acute infections that could be worsened by anticancer therapy or interfere with this study
* Patients must not have clinically significant cardiovascular disease, myocardial infarction within the past year (unstable angina), New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac dysrhythmia refractory to medical management, or peripheral vascular disease (Grade II or greater)
* Patients must not have uncontrolled hypertension
* Patients must not have history of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications
* Pregnant women are excluded from this study because BAY 43-9006 is a kinase inhibitor agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with BAY 43-9006, breastfeeding should be discontinued if the mother is treated with BAY 43-9006
* Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with BAY 43-9006; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated
* Patients must not have a clinical history of coagulopathy, bleeding diathesis or thrombosis; patients must not be on therapeutic anticoagulation; prophylactic anticoagulation (ie low dose warfarin) of venous access devices is allowed provided that INR \>= 1.5 is due to warfarin therapy; other patients with an INR \>= 1.5 are excluded
* Patients must not have a history of severe depression
* Concomitant treatment with rifampin, St. John's wort, and the cytochrome p450 enzyme-inducin antiepileptic drugs (phenytoin, carbamazepine or Phenobarbital)
C: Inclusion Criteria:

1. Patients with metastatic renal cell carcinoma
2. Patients with at least one measurable lesion
3. Patients with progressive metastatic renal cell carcinoma
4. Patients who had a prior partial or complete nephrectomy
5. Patients with a Karnofsky Performance Status ≥70%.
6. Adequate bone marrow function
7. Adequate liver function
8. Adequate renal function
9. Adequate coagulation profile

Exclusion Criteria:

1. 4 weeks post-major surgery
2. Patients who had radiation therapy within 28 days prior to start of study
3. Patients in need for major surgical procedure during the course of the study.
4. Patients with a serious non-healing wound, ulcer, or bone fracture.
5. Patients with a history of seizure(s) not controlled with standard medical therapy.
6. Patients who have received prior systemic treatment for their metastatic RCC.
7. Patients who received prior therapy with VEGF pathway inhibitor
8. Patients who have previously received systemic mTOR inhibitors
9. Patients with a known hypersensitivity RAD001 (everolimus) or other rapamycins or to its excipients.
10. Patients with history or current central nervous system (CNS) metastases or spinal cord compression.
11. Patients with a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment.
12. Patients with proteinuria at screening.
13. Patients with inadequately controlled hypertension
14. Patients receiving ongoing or with recent need for full therapeutic dose of oral or parenteral anticoagulants or chronic daily treatment with aspirin
15. Patients receiving chronic systemic treatment with corticosteroids or another immunosuppressive agent.
16. Patients with a known history of HIV
17. Patients with hypersensitivity to interferon alfa-2a or any component of the product.
18. Patients with an active, bleeding diathesis or coagulopathy or recurrent thromboembolism
19. Patients who have any severe and/or uncontrolled medical conditions or other conditions
20. Left Ventricular Ejection Fraction \< lower limit of institutional normal assessed by ECHO or MUGA
21. Patients who have a history of another primary malignancy ≤ 3 years
22. Female patients who are pregnant or breast feeding
23. Patients who are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to study treatment start.
24. Patients unwilling to or unable to comply with the protocol

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

* Written informed consent
* Histologically confirmed RCC of clear cell histology
* Confirmed metastatic RCC
* Age \>=18 years
* ECOG performance status of 0 or 1
* Life expectancy \>=3 months
* Prior nephrectomy
* Measurable disease, as defined by RECIST
* Use of an acceptable means of contraception (potentially fertile men and women)

Exclusion Criteria:

* RCC with predominantly sarcomatoid features
* Prior systemic or adjuvant therapy for RCC
* Prior radiotherapy for RCC within 28 days prior to Day 0, with the exception of single fraction radiotherapy given for the indication of pain control
* Treatment with Avastin, Tarceva, or other agents, either investigational or marketed, that act by either EGFR inhibition or anti-angiogenesis mechanisms
* 24-hour urine collection with \>=1 g of protein
* INR \>=1.5, except for subjects receiving warfarin therapy
* Serum creatinine \>2.0 mg/dL
* Serum calcium \>10 mg/dL (corrected)
* Absolute neutrophil count (ANC) \<1500/uL
* Platelet count \<75,000/uL
* Total bilirubin \>2.0 mg/dL
* AST or ALT \>5× the upper limit of normal (ULN) for subjects with documented liver metastases; \>2.5 × ULN for subjects without evidence of liver metastases
* LDH \>1.5× ULN
* Hemoglobin \<9 gm/dL (may be transfused or receive epoetin alfa \[e.g., Epogen\] to maintain or exceed this level)
* History of serious systemic disease, including myocardial infarction within the last 6 months, uncontrolled hypertension (blood pressure \>160/110 mmHg on medication), unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia, are eligible), or Grade II or greater peripheral vascular disease
* History of acute stroke within 6 months prior to randomization
* Patients on dialysis
* Other invasive malignancies, including bladder cancer and low-grade endometrial cancer, within 5 years of randomization (other than squamous or basal cell carcinoma of the skin)
* Pregnancy or breast feeding
* Inability to comply with study and/or follow-up procedures
* History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications
* Serious, non-healing wound, ulcer, or bone fracture
* Evidence of bleeding diathesis or coagulopathy
* History or clinical evidence of central nervous system or brain metastases
* History of bowel or gastric perforation
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study

  * Fine needle aspirations or core biopsies within 7 days prior to Day 0

Answer: C