Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Phase II Efficacy Assessment of Multiple MET Kinase Inhibitors (Cabozantinib [NSC #761968], Crizotinib [NSC #749005], Savolitinib [NSC #785348], and Sunitinib [NSC #736511]) in Metastatic Papillary Renal Carcinoma (PAPMET)
Brief Summary: This phase II trial studies how well cabozantinib s-malate, crizotinib, savolitinib, or sunitinib malate work in treating patients with kidney cancer that has spread from where it started to nearby tissue or lymph nodes or to other places in the body. Cabozantinib s-malate, crizotinib, savolitinib, and sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving cabozantinib s-malate, crizotinib, or savolitinib will work better in treating patients with kidney cancer compared to sunitinib malate.


Options:
A: 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
B: Inclusion Criteria:

* Confirmation of metastatic or recurrent renal cell carcinoma

Exclusion Criteria:

* Certain types of previous anti-cancer therapy for Renal Cell Carcinoma
* Patients with type I insulin-dependent diabetes or poorly-controlled type II insulin-independent diabetes
* Patients with a history of poorly controlled high blood pressure
C: Inclusion Criteria:

* Histologically and/or cytologically confirmed to have advanced renal cell carcinoma (RCC)
* Majority component of conventional clear-cell type is mandatory
* At least 1 measurable lesion (per RECIST)

Exclusion Criteria:

* Prior systemic treatment for RCC
* Evidence of current or prior central nervous system (CNS) metastases
* Cardiovascular disease
* Pregnant or nursing women
* Additional criteria applies
D: Inclusion Criteria:

* Has histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features
* Has locally advanced/metastatic disease (i.e., newly diagnosed Stage IV RCC per American Joint Committee on Cancer) or has recurrent disease
* Has measurable disease per RECIST 1.1 as assessed by the investigator/site radiologist
* Has received no prior systemic therapy for advanced RCC.
* Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
* Has Karnofsky performance status (KPS) ≥ 70% as assessed within 10 days prior to randomization.
* If receiving bone resorptive therapy (including but not limited to bisphosphonate or RANK-L inhibitor) must have therapy initiated at least 2 weeks prior to randomization.
* Demonstrates adequate organ function.
* Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug.
* Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study drug through 120 days after the last dose of study drug.

Exclusion Criteria:

* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to randomization.
* Has had major surgery within 4 weeks, received radiation therapy within 2 weeks prior to randomization, or has not recovered (i.e., ≤ Grade 1 or at baseline) from AEs due to prior treatment.
* Has had prior treatment with any anti-programmed cell death (anti-PD-1), or programmed cell death ligand 1 (PD-L1), or PD-L2 agent or an antibody targeting any other immune-regulatory receptors or mechanisms.
* Has received prior systemic anti-cancer therapy for RCC with vascular endothelial growth factor (VEGF)/VEGF receptors (VEGFR) or mechanistic target of rapamycin (mTOR) targeting agents.
* Has a history of severe hypersensitivity reaction (e.g., generalized rash/erythema, hypotension, bronchospasm, angioedema or anaphylaxis) to axitinib or sunitinib.
* Has a diagnosis of immunodeficiency OR is receiving a systemic steroid therapy exceeding physiologic corticosteroid dose or any other form of immunosuppressive therapy within 7 days prior to randomization, except in the case of central nervous system (CNS) metastases.
* Has an active autoimmune disease requiring systemic treatment with in the past 2 years OR a documented history of clinically severe autoimmune disease. Note: Participants with vitiligo, Sjøgren's syndrome, Type 1 diabetes, resolved childhood asthma/atopy, hypothyroidism or adrenal or pituitary insufficiency who are stable on hormone replacement, are not excluded.
* Has a known additional malignancy that has progressed or has required active treatment in the last 3 years. Note: Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ such as breast cancer in situ are acceptable if they have undergone potentially curative therapy.
* Has known active CNS metastases and/or carcinomatous meningitis.
* Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
* Has an active infection requiring systemic therapy.
* Has a known history of Human Immunodeficiency Virus (HIV).
* Has known active Hepatitis B or Hepatitis C infection.
* Has received a live virus vaccine within 30 days of randomization.
* Has a clinically significant gastrointestinal (GI) abnormality including:
* Malabsorption, total gastric resection
* Or any condition that might affect the absorption of orally taken medication
* Active GI bleeding, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy
* Intraluminal metastatic lesion with suspected bleeding, inflammatory bowel disease, ulcerative colitis or other GI condition associated with increased risk of perforation
* Has QT interval corrected for heart rate (QTc) ≥480 msec.
* Has a history of any of the following cardiovascular conditions within 12 months of randomization:
* Myocardial infarction
* Unstable angina pectoris
* Cardiac angioplasty or stenting
* Coronary/peripheral artery bypass graft
* Class III or IV congestive heart failure per New York Heart Association
* Cerebrovascular accident or transient ischemic attack
* Has a history of deep vein thrombosis or pulmonary embolism within 6 months of screening.
* Has poorly controlled hypertension defined as systolic blood pressure (SBP) ≥150 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg.
* Has evidence of inadequate wound healing.
* Has active bleeding disorder or other history of significant bleeding episodes within 30 days of randomization.
* Has hemoptysis within 6 weeks prior to randomization.
* Has current use (within 7 days of randomization) or anticipated need for treatment with drugs or foods that are known strong cytochrome P450 (CYP3A4/5) inhibitors.
* Has current use (within 7 days of randomization) or anticipated need for treatment with drugs that are known strong CYP3A4/5 inducers, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort; or drugs that are known with proarrhythmic potential.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
* Has had a prior solid organ transplant.
* Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study drug.

Answer: A