Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized, Multicenter, Open-label, Active-Controlled, Phase 2 Study of LY2510924 and Sunitinib Versus Sunitinib in Patients With Metastatic Renal Cell Carcinoma
Brief Summary: To compare the progression free survival of LY2510924 plus sunitinib therapy versus sunitinib in the first-line setting for patients with metastatic clear-cell renal cell carcinoma.


Options:
A: Inclusion Criteria:

* Pre-surgical criteria:

  * Patients must have primary-intact renal cell carcinoma, eligible for nephrectomy with curative intent
  * Tumors \>= 4 cm AND/OR macroscopic fully resectable nodes AND/OR surgically resectable renal vein thrombus AND/OR surgically resectable inferior vena caval thrombus by radiologic criteria to be clinically \>= pT1bNany (resectable) M0 disease
  * Multifocal ipsilateral renal cell carcinoma is allowed provided fully resectable and does not exceed inclusion criteria
* Patients must have no history of distant metastases
* No prior anti-cancer therapy for renal cell carcinoma is permitted in either the adjuvant or neoadjuvant setting; this includes metastectomy for renal cell carcinoma, or radiation therapy to the renal bed
* Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, 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 registration
* Patients must have no serious intercurrent illness including, but not limited to, the following: clinically significant cardiovascular disease (e.g. uncontrolled hypertension, myocardial infarction, unstable angina); New York Heart Association grade II or greater congestive heart failure; serious cardiac arrhythmia requiring medication; grade II or greater peripheral vascular disease; or psychiatric illness/social situations that would limit compliance with study requirements
* Patients must not have any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism
* Patient must not have ongoing ventricular cardiac dysrhythmias of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 grade \>= 2; patients with a history of serious ventricular arrhythmia (ventricular tachycardia \[VT\] or ventricular fibrillation \[VF\] \>= 3 beats in a row) are also excluded; additionally, patients with ongoing atrial fibrillation are not eligible
* Patients must have corrected QT (QTc) interval \< 500 msec on baseline electrocardiogram (EKG)
* Patient must not have hypertension that cannot be controlled by medications (\>= diastolic blood pressure 100 mm Hg despite optimal medical therapy)
* Patient must not have pre-existing thyroid abnormality with thyroid stimulating hormone that cannot be maintained in the normal range with medication
* If female, patient must not be pregnant or breastfeeding; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to pre-registration to rule out pregnancy; if pre-registration occurs prior to surgery, the blood or urine study must be repeated within 2 weeks prior to randomization to rule out pregnancy; (note: should a woman become pregnant while participating in this study, she should inform her treating physician immediately)
* Women of child-bearing potential and men must agree to use an accepted and effective method of contraception prior to study entry and for the duration of study participation; should a woman become pregnant while participating in this study, she should inform her treating physician immediately; if a man impregnates a woman while participating in this study, he should inform his treating physician immediately as well
* Patients with known human immunodeficiency virus (HIV) are excluded
* ELIGIBILITY CRITERIA FOLLOWING RADICAL OR PARTIAL NEPHRECTOMY
* The date of randomization must be less than 12 weeks after the date of surgery; patients must have recovered from any surgical related complications
* Within 4 weeks prior to randomization, patients must meet preoperative eligibility requirements
* Patients must have histologically or cytologically confirmed renal cell carcinoma. Using 2002 (American Joint Committee on Cancer \[AJCC\] 6th edition) TNM Staging, patients must be one of the following:

  * pT1b G3-4 N0 (or pNX where clinically N0) M0
  * pT2 G (any) N0 (or pNX where clinically N0) M0
  * pT3 G (any) N0 (or pNX where clinically N0) M0
  * pT4 G (any) N0 (or pNX where clinically N0) M0 or
  * T (any) G (any) N+ (fully resected) M0

    * Patients with microvascular invasion of the renal vein of any grade or stage (as long as M0) are also eligible
    * Patients must have undergone a full surgical resection (radical nephrectomy or partial nephrectomy) by either open or laparoscopic technique; clinical evidence of lymph node positivity requires removal of all clinically positive nodes; surgeons should designate extent of node dissection; all surgical specimens must have negative margins; patients with positive renal vein margins are eligible unless there is invasion of the renal vein wall at the margin (provided no other margins are positive)
* Patients must not have collecting duct carcinomas or medullary carcinomas
* Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* Patients must have an absolute baseline left ventricular ejection fraction (LVEF) of \>= 50% by multigated acquisition (MUGA) scan within 4 weeks prior to randomization
* Patients must have paraffin-embedded tumor specimen available for central core review of tumor histology and other correlative studies; tumor samples will be shipped as specified
* Patients must have no evidence of residual or metastatic renal cell cancer as documented on computed tomography (CT) scans of the chest, abdomen, and pelvis, all with oral and intravenous (IV) contrast (magnetic resonance imaging \[MRI\] scans of the abdomen and pelvis with gadolinium and a non-contrast CT of the chest may be substituted if patient is not able to have CT scans with intravenous contrast); patients unable to tolerate either gadolinium or IV contrast should not participate in this study (limitations to a patient's renal function should be taken into consideration when screening for this study)
* Scans must be obtained within 4 weeks of randomization; changes on these scans that are felt to be post surgical must be documented
* Patients without reported lymph nodes in the resected surgical specimen and a reported pathologic stage (post-nephrectomy) of pNX MUST undergo a post-operative contrast-enhanced CT scan (or MRI with gadolinium) within 4 weeks of randomization to document that there is no evidence of residual disease
* Patients must not be taking cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or phenobarbital), St John's Wort, ketoconazole, dexamethasone, the dysrhythmic drugs (terfenadine, quinidine, procainamide, sotalol, probucol, bepridil, indapamide or flecainide), haloperidol, risperidone, rifampin, grapefruit, or grapefruit juice within two weeks of randomization and during the course of therapy; (medications are not prohibited unless listed above); topical and inhaled steroids are permitted
* Patients must not receive any other investigational anti-cancer agents during the period on study
* Patients must not have a serious intercurrent illness, including ongoing or active infection requiring parental antibiotics
* Absolute granulocyte count (AGC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Serum creatinine =\< 2.0 x upper limit of normal (ULN) or calculated creatinine clearance (CrCl) \>= 30 mL/min (neither drug is cleared by the kidney)
* Total bilirubin =\< 1.5 x upper limit of normal (ULN)
* Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =\< 2.5 x ULN
* Patients must be able to swallow pills
B: 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
C: Inclusion Criteria:

* Evidence of histologically confirmed renal cell carcinoma (RCC) with metastases with a component of clear (conventional) cell histology
* A diagnosis of metastatic renal cell carcinoma (RCC) and have not received prior treatment with systemic (adjuvant or neoadjuvant) therapy for renal cell carcinoma (RCC) (including targeted therapy such as tyrosine kinase inhibitors or bevacizumab, immunotherapy, chemotherapy, hormonal, or investigational therapy)
* Evidence of measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Computed tomography (CT) or magnetic resonance imaging (MRI) should be performed within 4 weeks prior to study entry
* Participants who have or have not had their primary tumor removed by nephrectomy are allowed. Participants who have not had a nephrectomy should not be considered to need a nephrectomy as part of their overall therapy at the time of enrollment
* Performance status score of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
* Adequate bone marrow, liver, and renal function, as assessed by the following laboratory requirements, to be conducted within seven days prior to treatment: (upper limit of normal/lower limit of normal \[ULN/LLN\])

  * hemoglobin (greater than) \>8.0 g/dL (grams per deciliter)
  * absolute neutrophil count (ANC) (greater than or equal to) ≥1.5 × 10\^9/L (liter)
  * platelet count (greater than or equal to) ≥100 × 10\^9/L (liter)
  * total bilirubin (less than or equal to) ≤ 1.5 × ULN (upper limit of normal)
  * serum creatinine (less than or equal to) ≤2 × ULN (upper limit of normal)
  * alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (less than or equal to) ≤2.5 × ULN (upper limits of normal) \[or (less than or equal to) ≤5 × ULN (upper limits of normal) for patients with liver involvement of their cancer\]
  * Prothrombin Time (PT) or International Normalized Ratio (INR) and activated Partial Thromboplastin Time (aPTT) (less than or equal to) ≤1.5 x ULN (upper limit of normal)
* For women: Must be surgically sterile (surgical procedure: bilateral tubal ligation, hysterectomy, bilateral oophorectomy), post-menopausal (at least 12 consecutive months of amenorrhea), or have a negative pregnancy test. Women of childbearing potential should be compliant with a medically approved contraceptive regimen (intrauterine device \[IUD\], birth control pills, or barrier device) during and for 3 months after the treatment period; must have a negative serum pregnancy test within 7 days before study enrollment, and must not be breastfeeding
* For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 3 months after the treatment period
* Estimated life expectancy of at least 12 weeks
* Provide written informed consent/assent prior to any study-specific procedures
* No prior malignancies with the exception of stage 1 cancers definitively treated, carcinoma in situ (any primary site), treated non-melanoma skin cancer, superficial bladder tumors (Ta, Tis, and T1) or any cancer curatively treated 5 or more years prior to study entry
* Capable and willing to learn to self-administer LY2510924, or have a caregiver who is willing to learn and able to administer LY2510924 by subcutaneous (SC) injection and are able to swallow tablets
* Left ventricular ejection fraction (LVEF) greater than or equal to LLN as defined by the institution performing the scan, as assessed by Multiple Gated Acquisition (MUGA) scan, or from echocardiogram to be performed within 28 days prior to start of treatment

Exclusion Criteria:

* Received prior treatment with sunitinib or LY2510924
* Received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry
* History of active cardiovascular disease within the previous 12 months, including any of the following:

  * Myocardial infarction
  * Unstable angina
  * Coronary artery/peripheral artery bypass graft
  * Congestive heart failure
  * Malignant hypertension
  * Cerebrovascular accident or transient ischemic attack
  * Symptomatic cardiac arrhythmias (Patients with chronic, stable, rate- controlled atrial fibrillation are eligible)
* Exhibit uncontrolled hypertension ( \[greater than\] \>150/100 \[millimeters of mercury\] mm/Hg despite optimal medical therapy), or history of poor compliance with antihypertensive treatment
* Evidence of bleeding diathesis, National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 hemorrhage (less than) \<4 weeks of starting the study treatment, coagulopathy, or thromboembolic event
* Significant surgery (less than) \<4 weeks of starting study treatment or a minor surgical procedure (less than) \< 7 days prior to study treatment (Placement of a portacath or other venous access device does not require a waiting period)
* Suffer from medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
* Known or suspected allergy to any agent given in association with this trial
* Prior palliative radiotherapy to metastatic lesion(s) is/are permitted, provided there is at least 1 measurable lesion that has not been irradiated. Radiotherapy must have been completed (greater than) \>2 weeks prior to starting study treatment, and radiation-related side effects must have resolved
* Pregnant or lactating women
* Impairment of the gastrointestinal (GI) function or GI disease that may significantly alter the absorption of sunitinib
* Current or recent (within 10 days of first dose of study treatment) daily use of aspirin ( \[greater than\] \>325 \[milligram\] mg/day )
* Serious nonhealing wounds, acute or nonhealing ulcers, or bone fractures
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: C