Ziv-Aflibercept in Treating Patients With Metastatic or Unresectable Kidney Cancer

Inclusion Criteria:

* Histologically confirmed metastatic or unresectable renal cell carcinoma; disease must be conventional clear cell carcinoma or have a component of clear cell carcinoma
* Patient must have measurable lesions according to the Response Evaluation Criteria In Solid Tumors (RECIST); baseline measurements must be performed =\< 4 weeks prior to randomization
* Patient must have evidence of progressive disease following treatment with a tyrosine kinase inhibitor (TKI) as assessed by the site investigator on the basis of computed tomography (CT) scans and other appropriate clinical documentation
* Patient must have received at least one prior treatment with a VEGF receptor tyrosine kinase inhibitor for at least 12 weeks; prior treatment with either temsirolimus or everolimus is allowed; prior immunotherapy is limited to cytokine therapy with interleukin 2 and interferon alpha only
* Previous radiotherapy (RT) is permissible provided the measurable disease is outside the RT port; RT must be completed \>= 3 weeks prior to randomization
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Patient must have recovered from any toxic effects of prior radiotherapy or surgical procedures within 4 weeks prior to randomization
* Adequate organ function as defined in the protocol
* For women of childbearing potential, a negative serum pregnancy test is required within 1 week prior to randomization
* Women of childbearing potential and sexually active males must agree to use an accepted and effective method of contraception while on this study, and for 6 months after the completion of the study; if a woman becomes pregnant while she is on this study or within 6 months after the last dose of protocol therapy, she must inform her treating physician immediately; if a man impregnates a woman while he is on this study or within 6 months after the last dose of protocol therapy, he must inform his treating physician immediately
* Patients who have had basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal carcinoma in situ of the breast, or lobular carcinoma in situ of the breast within the past five years are eligible only if treated with curative intent; patients with other malignancies are eligible only if they have been continuously disease-free for \> 5 years prior to the time of randomization

Exclusion Criteria:

* True papillary, sarcomatoid features without any clear cell component, chromophobe, oncocytoma, collecting duct tumors and transitional cell carcinoma are not eligible
* Prior immunotherapy other than cytokine therapy with interleukin 2 and interferon alpha
* Prior treatment with bevacizumab
* Prior cellular therapy, vaccine, hormonal or chemotherapy for renal cell carcinoma; prior therapy for other cancers is allowable if therapy ended at least 5 years prior to enrollment
* History of metastatic central nervous system (CNS) disease
* Pregnant or breastfeeding
* Myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class III or IV congestive heart failure, cerebrovascular accident or transient ischemic attack within 24 weeks prior to randomization
* Prior pulmonary embolism, deep vein thrombosis, or other thromboembolic event
* History of uncontrolled or labile hypertension, with or without antihypertensive drug treatment, within 12 weeks prior to drug administration; this is defined as blood pressure \> 150/100 mm Hg or systolic blood pressure \> 180 mm Hg on at least 2 repeated determinations on separate days
* Active infection, evidence of bleeding or intratumoral bleeding, or underlying bleeding disorder
* History of hypersensitivity to any Trap agents or recombinant proteins
* Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy