Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3, Randomized, Open-Label Study of Nivolumab Combined With Cabozantinib Versus Sunitinib in Participants With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma
Brief Summary: The purpose of this study is to determine whether Nivolumab Combined with Cabozantinib is safe and effective compared to Sunitinib in previously untreated advanced or metastatic renal cell carcinoma


Options:
A: For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

* Histological confirmation of RCC with a clear-cell component, including participants who may also have sarcomatoid features
* 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:

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

Exclusion Criteria:

* Any active CNS metastases
* Any active, known or suspected autoimmune disease
* Any condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization
* Participants who have received a live/attenuated vaccine within 30 days of first treatment

Other protocol defined inclusion/exclusion criteria could apply
B: Inclusion Criteria:

1. Adult males and females: ≥18 years of age.
2. Locally advanced or metastatic, histological confirmed, non-clear cell RCC of all subtypes. Patients must have advanced non-clear cell of one of the following subtypes: papillary, chromophobe, collecting duct carcinoma (CDC), renal medullary carcinoma (RMC), or unclassified.
3. Patients with measurable disease (at least one uni-dimensionally measurable target lesion by CT-scan or MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) If prior palliative radiotherapy to metastatic lesions: ≥ 1 measurable lesion that has not been irradiated.
4. PS 0-2 ECOG
5. Signed written informed consent.
6. White blood cell count (WBC) ≥4x10\*9/L with neutrophils ≥1.5 x 10\*9/L, platelet count ≥100x10\*9/L, hemoglobin ≥9 g/dL.\]
7. Total bilirubin \<2 x upper limit of normal.
8. AST and ALT \<2.5 x upper limit of normal, or \<5 x upper limit of normal in case of liver metastases.
9. Serum creatinine \<2.0 x upper limit of normal.
10. Normal ECG without QT prolongation (QTc \< 450msec).
11. Adequate cardiac function (left ventricular ejection fraction \> 40% as assessed by ECHO.

Exclusion Criteria:

1. Predominant clear-cell RCC
2. Resectability or other curative options
3. Any investigational drug within the 30 days before inclusion.
4. Prior systemic treatment for their RCC.
5. Known or suspected allergy or hypersensitivity reaction to any of the components of study treatments.
6. Radiotherapy within the last 4 weeks.
7. Pregnancy (absence to be confirmed by beta-hCG test) or lactation period.
8. Men or women of child-bearing potential who are sexually active and unwilling to use a medically acceptable method of contraception during the trial.
9. Clinically symptomatic brain or meningeal metastasis. (known or suspected)
10. Cardiac arrhythmias requiring anti-arrhythmics (excluding beta blockers or digoxin).
11. History of any of the following cardiac events within the past 6 months:

    * myocardial infarction (including severe/unstable angina),
    * coronary/peripheral artery bypass graft,
    * congestive heart failure (CHF),
    * cerebrovascular accident,
    * transient ischemic attack,
    * pulmonary embolism.
12. No hemorrhage ≥ grade 3 within the past 4 weeks
13. Uncontrolled severe hypertension (failure of diastolic blood pressure to fall below 90 mm Hg despite the use of ≥3 anti-hypertensive drugs
14. History of relevant pulmonary hypertension or interstitial lung disease.
15. Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease or chronic diarrhea
16. Previous malignancy (other than renal cancer cancer) in the last 5 years except basal cell cancer of the skin, pre-invasive cancer of the cervix or superficial bladder tumor \[Ta, Tis and T1\].
17. History of organ allograft
18. Significant disease which, in the investigator's opinion would exclude the patient from the study
19. Patients with seizure and epileptic disorder or other conditions requiring medication (such as phenytoin, carbamazepin, phenobarbital)
20. Patients under strong inducers or inhibitors to CYP Isoenzymes
21. Patients with hypersensitivity to the antihistamine or patients who cannot receive the antihistamine for other medical reasons
22. Patients requiring long-term cortisone therapy
23. Patients requiring oral anticoagulation treatment, such as marcoumar. (Anticoagulation treatment with heparin or low molecular weight heparin \[LMWH\] is allowed provided that close monitoring is performed).
24. Surgery within at least 2 weeks prior to randomization
25. HIV seropositivity.
26. Abnormal pulmonary function (DLCO \< 50%). \[Pulmonary function tests need only to be performed if abnormal pulmonary function present in medical history\].
27. Poorly controlled diabetes mellitus.
28. Liver cirrhosis, chronic hepatitis
29. Legal incapacity or limited legal capacity
30. Known alcohol or drug abuse.
31. Medical or psychological conditions that would not permit the patient to complete the study or sign informed consent.
C: Inclusion Criteria:

* Patients will be required to have the clear cell variant of renal cell carcinoma with less than 25% of any other histology (including, but not limited to, papillary or chromophobe or oncocytic); there must be histologic confirmation by treating center of either primary or metastatic lesion
* Patients will be required to have measurable metastatic disease that is not curable by standard radiation therapy or surgery; all sites must be assessed within 4 weeks prior to study entry
* Previous nephrectomy is required with the following exceptions:

  * Primary tumor =\< 5 cm, or
  * Extensive liver (\> 30% of liver parenchymal) or multiple (\> 5) bone metastases, making nephrectomy a clinically questionable procedure
  * Unresectable primary tumor due to invasion into adjacent organs or encasing the aorta or vena cava
* No prior cytotoxic chemotherapy; a maximum of one prior regimen of either vaccine or cytokine-based immunotherapy disease is permitted
* No prior anti-angiogenic therapy including, but not limited to, SU11248, ZD6474 or VEGF Trap; no prior therapy with bevacizumab, mammalian target of rapamycin (mTOR) inhibitors (including, but not limited to, temsirolimus), or sorafenib will be allowed; thalidomide or interferon alpha (IFNalpha) are allowed either for adjuvant therapy or stage IV disease
* No immunotherapy within 4 weeks of randomization; toxicities from immunotherapy must have resolved and a minimum of two weeks must pass prior to enrollment
* Prior radiation therapy is permitted, but toxicities from radiation must have resolved and a minimum of 2 weeks must pass prior to randomization
* No history or clinical evidence of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastasis, or history of stroke within the past 48 weeks
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Life expectancy of greater than 12 weeks
* Hemoglobin (Hgb) \>= 9.0 g/dL (transfusions allowed prior to enrollment)
* White blood count (WBC) \>= 3,000/mm\^3
* Absolute granulocyte count (AGC) \>= 1,200/mm\^3
* Platelet count \>= 100,000/mm\^3
* Serum creatinine =\< 1.5 x upper limit of normal (ULN) or serum creatinine clearance (CrCl) \>= 55 ml/min
* Total bilirubin =\< 1.5 x ULN
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN (or =\< 5.0 x ULN in the presence of liver metastases)
* International normalized ratio (INR) =\< 1.5
* Activated partial thromboplastin time (aPTT) within normal limits
* Fasting cholesterol \< 350 mg/dL (9.0 mmol/L)
* Fasting triglycerides \< 400 mg/dL (4.56 mmol/L)
* Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, and ductal or lobular carcinoma in situ of the breast; patients with other malignancies are eligible if they have been continuously disease-free for \>= 5 years prior to the time of randomization
* No history of allergic reactions attributed to Chinese hamster ovary cell products, other recombinant human antibodies, or compounds of similar chemical or biologic composition to sorafenib, temsirolimus or bevacizumab
* No history of bleeding diathesis or coagulopathy
* Any condition that impairs patient's ability to swallow pills will make patient ineligible
* No major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization
* No anticipated need for major surgery during the course of the study
* No current or recent (within 4 weeks of enrollment) use of full-dose of anticoagulants or thrombolytic agents (except as required to maintain patency of preexisting or permanent indwelling IV catheters, for those patients receiving warfarin, INR must be =\< 1.5)
* No clinically significant cardiovascular disease, defined as one of the following:

  * Patients with uncontrolled hypertension (blood pressure \> 150/100 mm/Hg at the time of enrollment); patients with hypertension and blood pressure =\< 150/100 mm/Hg on stable antihypertensive regimen are eligible
  * Myocardial infarction or unstable angina \< 24 weeks prior to registration
  * New York Heart Association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris
  * Grade II or greater peripheral vascular disease
* No serious, non-healing wound, ulcer, or bone fracture
* No significant proteinuria at baseline; urine protein must be screened within 2 weeks prior to randomization by urine analysis for urine protein creatinine (UPC) ratio; if UPC ratio is \> 0.5, 24-hour urine protein is to be obtained and the level must be \< 1000 mg for patient enrollment

  * NOTE: UPC ratio of spot urine is an estimation of the 24 urine protein excretion; a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm
* No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on day 0 or psychiatric illness/social situations that would limit compliance with study requirements
* Patients currently taking any of the following cytochrome P450 enzyme-inducing drugs are ineligible:

  * Phenytoin
  * Carbamazepine
  * Phenobarbital
  * Rifampin
* Pregnant and breastfeeding women are excluded from the study; breastfeeding should be discontinued while receiving therapy; patients must have pregnancy test within 7 days prior to patient randomization if woman is of child-bearing capacity
* Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study
D: 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.

Answer: A