Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomised, Open Label, Parallel Group Phase II Study Comparing the Efficacy and Tolerability of BIBF 1120 Versus Sunitinib in Previously Untreated Patients With Renal Cell Cancer
Brief Summary: Compare safety and efficacy of BIBF 1120 versus sunitinib in patients with advanced RCC and to investigate the effects of BIBF 1120 on the heart rate (HR) corrected QT interval (QTcF).


Options:
A: 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.
B: Inclusion Criteria:

* Renal cell carcinoma with a predominant clear cell component confirmed by histology.
* Advanced disease: metastatic AND, not suitable for resection
* Male or female, aged 18 years or older
* ECOG (Eastern Cooperative Oncology Group) Performance Status of 0 or 1
* Low or intermediate MSKCC (Memorial Sloan Kettering Cancer Center) prognostic risk score,i.e. no more than 2 of the following:

  * Karnofsky performance status (\<80%)
  * Low serum hemoglobin (≤ 13 g/dL for males and ≤ 11.5 g/dL for females)
  * High corrected serum calcium (≥ 10 mg/dL)
* Target and/or non-target lesions according to RECIST 1.1 ( Response Evaluation Criteria in Solid Tumors)
* Expected survival of at least 3 months.
* No prior systemic treatment. But adjuvant treatment is ok if stopped from ≥ 24 months
* Adequate bone marrow function as shown by:
* Adequate liver function as shown by:
* Adequate renal function as shown by serum creatinine ≤ 1.5 x ULN (upper limit of normal)
* Left ventricular ejection fraction ≥55% on gated cardiac blood pool scan, or normal left ventricular function and fractional shortening on echocardiogram (according to institutional limits).
* SBP (systolic blood pressure) ≤140mmHg and DBP (diastolic blood pressure)

  * 90mmHg (it is acceptable to initiate antihypertensive treatment prior to registration to achieve these goals).
* Able to commence treatment within 7 days of registration.
* Willing and able to comply with follow-up and all other protocol requirements.
* Written informed consent

Exclusion Criteria:

* Prior treatment with VEGF-targeting agents or multi-kinase inhibitors or mTOR-targeting agents
* Active central nervous system metastases.
* Other malignancy diagnosed within the last 5 years, except the following if adequately treated: superficial squamous cell carcinoma or basal cell carcinoma of skin, superficial bladder cancer (T1 and G1 or T1 and G2), stage 1 cervical cancer.
* Treatment with an investigational agent in the last 4 w.
* Known to be HIV positive.
* Evidence of chronic hepatitis due to hepatitis B virus (HBV) or hepatitis C virus (HCV)
* Clinically significant heart disease (NYHA Class III or IV)
* History of hypertension requiring hospitalization.
* Other serious illnesses,
* Immunotherapy or chemotherapy in the last 4 w (6 weeks for nitrosoureas)
* Major surgery in the last 4 w, or planned in the next 6 w
* Radiation therapy in the last 2 w, or planned in the next 6 w
* NCI CTCAE (Common Toxicity Criteria for Adverse Effects) version 4.0 grade 3 or worse hemorrhage in last 4 w.
* Any of the following in the last year: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
* Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication.
* Ongoing cardiac dysrhythmias of NCI CTCAE version 4.0 grade ≥2, atrial fibrillation of any grade, or prolongation of the corrected QT interval (QTc) to \>450 msec for males or \>470 msec for females
* Uncontrolled diabetes as defined by fasting serum glucose \>1.5 X ULN.
* Pregnancy,lactation. Inadequate contraception.
* Known allergy or hypersensitivity to everolimus, sunitinib or iodine.
* Medical or psychiatric condition that compromises the patient's ability to give informed consent.
C: 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
D: Inclusion criteria:

1. Patients with unresectable or metastatic Renal Cell Cancer, who have received no previous systemic anti-cancer treatment.
2. Histological-confirmed diagnosis of renal cell cancer with clear cell component.
3. Acceptable renal,liver,cardiovascular,bone marrow and other functions to allow sunitinib/BIBF 1120 treatment.

Exclusion criteria:

1. Patients unable to tolerate Sunitinib/BIBF 1120 treatment
2. Treatment with other investigational drugs or participation in another clinical study within the past 4 weeks before start of therapy or concomitantly with this study.
3. Patients unable to comply with the 1199.26 protocol.
4. Pregnancy or breast feeding.
5. Active alcohol or drug abuse.
6. Women of child bearing potential, or men who are able to father a child, unwilling to use a medically acceptable form of contraception during the study period.

Answer: D