The purpose of this study is to determine whether ramucirumab is effective treatment in participants with metastatic renal cell carcinoma who have developed progressive disease or become intolerant to tyrosine kinase inhibitor therapy.

The Primary objective is to determine the best objective response rate (ORR) of ramucirumab when administered to participants with metastatic renal cell carcinoma (RCC) whose disease has progressed during therapy with a tyrosine kinase inhibitor (TKI, sunitinib and/or sorafenib) or who have developed intolerance to these agents.

Inclusion Criteria:

• The participant has histologically or cytologically confirmed clear cell RCC
• The participant is ≥ 18 years of age
• The participant has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 or Karnofsky Performance Status (KPS) ≥ 80%
• The participant has had a prior nephrectomy (as therapy for RCC)
• The participant has metastatic RCC
• The participant has a life expectancy of > 3 months
• The participant has measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
• The participant has received prior therapy with a TKI (sunitinib and/or sorafenib) with either disease progression on TKI therapy (progression within 60 days of the last dose of TKI) or intolerance to TKI (unable to continue therapy because of side-effects). A participant with progression during a protracted treatment break is not eligible unless the participant has had progression or intolerance as defined above
• The participant has resolution of all clinically significant toxic effects of prior cancer therapy to grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0 (NCI-CTCAE)
• The participant has adequate hematological functions [absolute neutrophil count (ANC) ≥ 1500 cells per milliliter (cells/mL), hemoglobin ≥ 9 grams per deciliter (g/dL) and platelets ≥ 100,000 cells/mL]
• The participant has adequate hepatic function [bilirubin within normal limits (WNL), aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤ 2.5 times the upper limit of normal (ULN), or ≤ 5.0 times the ULN if the transaminase elevation is due to liver metastases]
• The participant has normal renal function or mild renal dysfunction [creatinine ≤ 2.2 milligrams per deciliter (mg/dL)]
• The participant's urinary protein ≤ 1+ on dipstick or routine urinalysis [(UA); if urine dipstick or routine analysis is ≥ 2+, a 24-hour urine for protein must demonstrate < 1000 (milligrams) mg of protein in 24 hours to allow participation in the study]
• The participant must have adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.8 and a partial thromboplastin time (PTT) ≤ 1.5 X ULN. Participants on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight (LMW) heparin and if on warfarin must have a INR between 2 and 3 and have no active bleeding or pathological condition that carries a high risk of bleeding (for example, tumor involving major vessels or known varices)
• The participant is able to provide informed written consent
• The participant , if sexually active, is postmenopausal (last menstrual period > 2 years prior to study), surgically sterile, or is using effective method of contraception in the opinion of the investigator
• The participant , if female, must have a negative serum pregnancy test upon entry into this study
• The participant has a normal thyroid stimulating hormone (TSH) value. Participants with an abnormal TSH may be eligible provided they meet all other eligibility criteria and have ECOG performance status 0-1. Participants with an abnormal TSH value require a full thyroid evaluation prior to enrollment. Endocrinology consultation may be performed at the discretion of the investigator
• The participant has serum calcium within normal limits

Exclusion Criteria:

• The participant has received prior treatment with bevacizumab
• The participant has known brain or leptomeningeal metastases
• The participant has received >2 prior cytotoxic chemotherapy regimens for RCC
• The participant has received antitumor therapy (biologic agents, major surgery, or investigational agent) within 28 days prior to enrollment on study. The participant has received radiation therapy within 14 days prior to enrollment on study. Participants with metastasis in weight bearing bones at high risk for pathologic fracture may participate provided that appropriate surgical intervention and/or radiation therapy is undertaken and completed at least 28 days prior to enrollment
• The participant has received > 1 prior bio-immunotherapy regimens (defined as either interleukin-2 or interferon alpha given as monotherapy, concurrently, or sequentially as planned)
• The participant has a concurrent active malignancy other than adequately treated non-melanomatous skin cancer or other non-invasive carcinoma or in situ neoplasm. A participant with previous history of malignancy is eligible, provided that he/she has been disease free for > 3 years
• The participant has a nonhealing wound or ulcer
• The participant has a known alcohol or drug dependency
• The participant is pregnant or breastfeeding
• The participant has a coexisting medical or psychiatric problem of sufficient severity to limit compliance with the study and/or increase the risks associated with study participation or study drug administration or interfere with the interpretation of study results
• The participant has an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorders in the opinion of the investigator
• The participant has known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness