Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II Clinical Trial to Evaluate the Efficacy of BAY 43-9006 With or Without Low Dose Interferon in Metastatic Renal Cell Carcinoma
Brief Summary: This randomized phase II trial is studying sorafenib and interferon alfa-2b to see how well they work compared to sorafenib alone in treating patients with metastatic kidney cancer. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Interferon alfa-2b may interfere with the growth of tumor cells. Sorafenib and interferon alfa-2b may also block blood flow to the tumor. Giving sorafenib together with interferon alfa-2b may kill more tumor cells.


Options:
A: 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)
B: Inclusion Criteria:

* Patients who give written informed consent prior to any study specific screening procedures with the understanding that the patient has the right to withdraw from the study at any time, without prejudice
* Male or female patients \>= 18 years of age
* Patients who have a life expectancy of at least 12 weeks
* Patients, who suffer from unresectable and/or metastatic, measurable predominantly clear cell RCC (Renal Cell Carcinoma) histologically or cytologically documented
* Patients must have undergone prior (at the time of primary diagnosis) complete surgical excision of primary RCC tumor
* Patients must have had no prior systemic therapy for advanced RCC. Prior systemic therapy is defined as any treatment with a chemotherapy agent (or regimen), an immunotherapy agent (or regimen) or an investigational treatment agent (or regimen) against the renal cell carcinoma. Megestrol acetate or medroxyprogesterone will constitute as a prior systemic therapy
* Patients who have at least one uni-dimensional measurable lesion by CT (Computed tomography)-scan or MRI (Magnetic resonance imaging) according to Response Evaluation Criteria in Solid Tumors (RECIST)
* Patients who have an Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1
* Adequate bone marrow, liver , and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening
* Hemoglobin \>9.0 g/l
* Absolute neutrophil count ( ANC)\>1,500/mm3
* Platelets\> or = 100,000/ul
* Total bilirubin \< 1.5 x the upper limit of normal
* ALT (Alanine aminotransferase) and AST (Aspartate aminotransferase) \< 2.5 x upper limit of normal (\< 5 x upper limit of normal for patients with liver involvement of their cancer)
* Amylase and lipase \< 1.5 x the upper limit of normal
* Serum creatinine \< 2.0 x the upper limit of normal
* PT (Prothrombin Time) or INR (International Normalized Ratio) and PTT (Partial Thromboplastin Time) \< 1.5 x upper limit of normal (patients who receive anti-coagulation treatment with an agent such as warfarin or heparin will be allowed to participate. For patients on warfarin, close monitoring of at least weekly evaluations will be performed until INR is stable based on a measurement at pre dose, as defined by the local standard of care)

Exclusion Criteria:

* Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta \[Noninvasive papillary carcinoma\], Tis \[Carcinoma in situ: "flat tumor"\]\&T1 \[Tumor invades subepithelial connective tissue\]) or any cancer curatively treated \> 5 years prior to study entry
* Complete renal shut-down requiring hemo- or peritoneal dialysis
* History of cardiac disease : congestive heart failure \> NYHA (New York Heart Association) class 2: active cardiovascular disease( MI (Distant metastasis) more than 6 months prior to study entry is allowed); cardiac arrhythmia requiring anti-arrythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension
* Active clinically serious bacterial or fungal infections (\>= grade 2 NCI-CTCAE (National Cancer Institute-Common Terminology Criteria for Adverse Events), Version 3)
* Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
* Symptomatic metastatic brain or meningeal tumors unless the patient is \> 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to this brain tumour site at the time of study entry. Also the patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies (head CT or MRI at screening always required)
* Patients with seizure disorder requiring medication (such as steroid anti-epileptics)
* History of organ allograft
* Substance abuse, 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 the investigational agent or any agent given in association with this trial
* Any condition that is unstable or which could jeopardise the safety of the patient and his/her compliance in the study
* Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial
C: Inclusion Criteria:

* Patients must have histologically or cytologically confirmed papillary histology renal cell carcinoma which is metastatic or locally advanced disease not amenable to surgical resection; (NOTE: a designation of type I or type II should be made by the local pathologist if possible); mixed histologies containing type I or type II will be allowed provided that they contain \>= 50% of the papillary component
* Patients must also have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension; disease X-rays, scans or physical examinations used for tumor measurement must have been completed within 28 days prior to registration; if there is clinical suspicion for bone metastases at the time of enrollment (at the discretion of the investigator), bone scan should be performed at baseline (within 42 days prior to registration); all disease must be assessed and documented on the Baseline Tumor Assessment form
* Patients with a history of treated brain metastases who are asymptomatic and have not received steroid therapy in the 14 days prior to registration are eligible; anti-seizure medications are allowed provided they are non-enzyme inducing (e.g. topiramate, levetiracetam, gabapentin)
* Patients must not have cavitating pulmonary lesions; patients must not have tumor invading the gastrointestinal (GI) tract or evidence of endotracheal or endobronchial tumor within 28 days prior to registration
* Patients may have received prior surgery; at least 28 days must have elapsed since surgery and patient must have recovered from any adverse effects of surgery
* Patients may have received up to one prior systemic therapy for advanced or metastatic renal cell carcinoma with the exception of another VEGF inhibitor Food and Drug Administration (FDA)-approved for advanced renal cell carcinoma (RCC) (i.e., pazopanib, bevacizumab, sorafenib or axitinib); if a patient develops metastatic disease within six months of discontinuation of adjuvant therapy, this will constitute one prior systemic therapy for advanced or metastatic RCC; if a patient develops metastatic disease and more than six months has elapsed since discontinuation of adjuvant therapy, this will not constitute prior systemic therapy for advanced or metastatic RCC; patients may have also received prior immunotherapy; patients must not have received a MET/hepatocyte growth factor (HGF) inhibitor or sunitinib as prior therapy; at least 14 days must have elapsed since completion of prior systemic therapy; patients must have recovered from all associated toxicities at the time of registration
* Patients may have received prior radiation therapy, but must have measurable disease outside the radiation port; at least 14 days must have elapsed since completion of prior radiation therapy; patients must have recovered from all associated toxicities at the time of registration
* Patients must not be taking, nor plan to take while on protocol treatment, strong CYP3A4 inhibitors (e.g. boceprevir, cobicistat, danoprevir, elvitegravir/RIT, fluvoxamine, indinavir, itraconazole, ketoconazole, lopinavir/RIT, nefazodone, nelfinavir, posaconazole, ritonavir, telaprevir, telithromycin, tipravavir/RIT, or voriconazole); strong CYP3A4 inducers (e.g. avasimibe, phenytoin, rifampin, rifabutin); potent inhibitors of CYP1A2 (e.g. ciprofloxacin); and/or drugs known to be CYP3A4 substrates with a narrow therapeutic range (e.g., diergotamine, ergotamine) within 14 days prior to randomization; moderate inhibitors or inducers of isoenzyme CYP3A4 should be avoided, but if necessary can be used with caution
* Patients must not be receiving or planning to receive any other investigational agents
* Patients must have a complete physical examination and medical history within 28 days prior to registration
* Patients must have a Zubrod performance status of 0 - 1
* White blood cell count (WBC) \>= 2,000/mcL (must be obtained within 28 days prior to registration)
* Absolute neutrophil count (ANC) \>= 1,000/mcL (must be obtained within 28 days prior to registration)
* Platelet count \>= 75,000/mcL (must be obtained within 28 days prior to registration)
* Serum bilirubin =\< 1.5 x institutional upper limits of normal (ULN) (must be obtained within 28 days prior to registration)
* Serum transaminase (serum glutamic oxaloacetic transaminase \[SGOT\]/aspartate aminotransferase \[AST\] and serum glutamate pyruvate transaminase \[SGPT\]/alanine aminotransferase \[ALT\]) must be =\< 2.5 x the institutional ULN unless the liver is involved with the tumor, in which case serum transaminase (SGOT/SGPT) must be =\< 5 x the institutional ULN (must be obtained within 28 days prior to registration)
* Serum creatinine must be =\< 2 x the institutional ULN OR creatinine clearance (either measured or calculated) must be \> 30 mL/min (must be obtained within 28 days prior to registration)
* Patients must not have any clinical evidence of congestive heart failure (CHF) (specifically, New York Heart Association \[NYHA\] class III \[moderate\] or class IV \[severe\]) at the time of registration; baseline echocardiogram within 28 days of registration must demonstrate an ejection fraction (EF) \>= 50%; due to the potential cardiac toxicity of the agents utilized in this protocol, patients must have corrected QT (QTc) interval \< 500 msec on prestudy electrocardiogram (EKG) and no known history of congenital long QT syndrome; patients must not have experienced unstable angina pectoris, clinically significant cardiac arrhythmias, or stroke (transient ischemic attack \[TIA\] or other ischemic event) within 3 months prior to registration and not have experienced myocardial infarction or thromboembolic event requiring anticoagulation within 6 months of registration; prestudy EKG must be obtained within 28 days prior to registration
* Baseline urinalysis should show urine protein \< 3+ and must be obtained within 28 days prior to registration; if urine protein is 3+ or greater, then urine protein by 24 hour collection must show less than 3 grams of protein
* Patients must not have inadequately controlled hypertension; patients must have documented blood pressures of systolic blood pressure (SBP) \< 150 and diastolic blood pressure (DBP) \< 90 within 14 days of starting randomization; blood pressure medications (any number) are permitted
* Patients must be able to take oral medications (i.e., swallow pills whole); patients must not have gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation, prior surgical procedures that could in the opinion of the treating investigator affect absorption, or active peptic ulcer disease; patients with intractable nausea or vomiting are not eligible
* Patients must not have had any clinically-significant GI bleeding within 6 months prior to registration and patients must not have a GI disorder which (at the discretion of the investigator) bears a high risk of perforation or fistula; examples of this include (but are not limited to) Crohn's disease or tumor with transmural extension through the gastrointestinal lining
* Patients must not have had hemoptysis of \>= 0.5 teaspoon (2.5 ml) of red blood within 3 months prior registration
* Patients must not demonstrate any other signs indicative of pulmonary hemorrhage within 3 months prior to registration
* Patient's baseline imaging must not indicate the presence of tumor invading or encasing any major blood vessels
* Patients must not have any unresolved wounds from previous surgery
* Albumin, alkaline phosphatase, bicarbonate, blood urea (BUN), chloride, glucose, phosphorus, and total protein must be assessed within 28 days of registration
* No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for 3 years; men receiving active surveillance for prostate cancer may also be enrolled
* Due to the unknown effects of the study drugs, patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method while receiving study drug and for three months after last dose of study drug; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
* Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with cabozantinib, crizotinib, savolitinib or sunitinib; in addition these patients are at increased risk of lethal infections when treated with marrow suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
* Patients must be \>= 18 years of age
* Patients must have tissue available and be willing to submit for independent pathologic review in order to classify type I versus type II papillary disease
* Patients must be offered the opportunity to participate in specimen banking for future translational medicine studies
* Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
* As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
D: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed renal cell carcinoma (RCC)

  * Conventional clear cell carcinoma
  * Metastatic or unresectable disease
* The following characteristics and cellular types are excluded:

  * True papillary
  * Sarcomatoid features without a clear cell component
  * Chromophobe
  * Oncocytoma
  * Collecting duct tumor
  * Transitional cell carcinoma
* Measurable or nonmeasurable disease, including any of the following:

  * Unidimensionally measurable lesion ≥ 20 mm by conventional techniques (e.g., physical exam or chest x-ray) OR 10 mm by spiral CT scan or MRI
  * The following are considered nonmeasurable disease:

    * Small lesions
    * Bone lesions
    * Leptomeningeal disease
    * Ascites
    * Pleural/pericardial effusion
    * Lymphangitis cutis/pulmonis
    * Abdominal masses that are not confirmed and followed by imaging techniques
    * Cystic lesions
    * Irradiated lesions, unless progression is documented after radiotherapy
* RCC paraffin tissue blocks or unstained slides must be available
* No evidence of prior or concurrent CNS metastases by MRI or CT scan

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* Karnofsky 70-100%

Life expectancy

* Not specified

Hematopoietic

* Granulocyte count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* No history of clinically significant bleeding

Hepatic

* AST/ALT ≤ 2.5 times upper limit of normal (ULN)
* Alkaline phosphatase ≤ 2.5 times ULN
* Bilirubin ≤ 1.5 times ULN

Renal

* Creatinine ≤ 1.5 times ULN
* No proteinuria \> 1+

  * Proteinuria ≥ 2+ allowed provided protein is \< 2 g/24-hour urine collection

Cardiovascular

* No deep venous thrombosis within the past year
* No cerebrovascular accident within the past year
* No peripheral vascular disease with claudication on \< 1 block
* No uncontrolled hypertension defined as blood pressure ≥160 mm Hg (systolic) and/or ≥ 90 mm Hg (diastolic) while on medication
* No New York Heart Association class II-IV congestive heart failure
* No angina pectoris requiring nitrate therapy
* No myocardial infarction within the past 6 months
* No other significant cardiovascular disease

Pulmonary

* No pulmonary embolus within the past year
* No ongoing hemoptysis

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 3 months after study treatment
* No preexisting thyroid abnormality in which normal thyroid function cannot be maintained by medication
* No delayed wound healing, ulcers, or bone fractures
* No uncontrolled psychiatric disorder
* No other currently active\* malignancy except nonmelanoma skin cancer NOTE: \*Disease is not considered currently active if patient completed anticancer therapy and is considered to have \< 30% risk of relapse

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No prior systemic immunotherapy for RCC
* No prior thalidomide, anti-vascular endothelial growth factor (VEGF) therapy, VEGF receptor inhibitors, or antiangiogenic treatment of any kind
* No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy

* No prior systemic chemotherapy for RCC
* No concurrent chemotherapy

Endocrine therapy

* No concurrent systemic corticosteroid therapy except the following:

  * Topical and inhaled steroids
  * Replacement therapy for adrenal insufficiency
* No concurrent hormones except those administered for nondisease-related conditions (e.g., insulin for diabetes)

Radiotherapy

* See Disease Characteristics
* At least 4 weeks since prior radiotherapy and recovered
* Prior palliative radiotherapy to metastatic lesions allowed provided at least 1 measurable or nonmeasurable lesion remains untreated
* No concurrent palliative radiotherapy

Surgery

* At least 4 weeks since prior major surgery and recovered

Other

* No other prior systemic investigational therapy for RCC
* No other prior adjuvant or neoadjuvant systemic therapy for RCC
* No concurrent full-dose oral or parenteral anticoagulation\* NOTE: \*Low-dose (1 mg) warfarin for maintenance of catheter patency and/or daily prophylactic aspirin is allowed

Answer: A