Study of Icrucumab (IMC-18F1) or Ramucirumab Drug Product (DP) in Combination With Capecitabine or Capecitabine on Previously Treated Breast Cancer Patients

Inclusion Criteria:

The participant has histologically or cytologically confirmed breast cancer which at the time of study entry is either Stage III disease not amenable to curative therapy or Stage IV disease
Has measurable or nonmeasurable disease
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Has received prior anthracycline therapy
Has received prior taxane therapy
Participants with human epidermal growth factor receptor-2 (HER2) positive disease must have progressed on or following trastuzumab
Participants with hormone receptor-positive disease must have progressed on or following hormone therapy
Has received ≤ 3 prior chemotherapy regimens in any setting (a regimen is defined as any agent[s] that has been administered for more than 1 cycle; sequential neoadjuvant/adjuvant treatment is considered 1 regimen)
Has completed any prior radiotherapy ≥ 4 weeks prior to randomization
Has completed any prior hormonal therapy ≥ 2 weeks prior to randomization
Has adverse events (AEs) that have resolved to Grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v 4.0) from all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy,or hormonal therapy
Has adequate hematologic, coagulation, hepatic and renal function

Does not have:

cirrhosis at a level of Child-Pugh B (or worse) or
cirrhosis (any degree) and a history of hepatic encephalopathy or ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis
Has urinary protein is ≤ 1+ on dipstick or routine urinalysis; if urine protein ≥ 2+, a 24-hour urine collection must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study
Agrees to use adequate contraception during the study period and for 12 weeks after the last dose of study medication

Exclusion Criteria:

Has a concurrent active malignancy other than adequately treated nonmelanomatous skin cancer, curatively treated cervical carcinoma in situ, or other noninvasive carcinoma or in situ neoplasm. A participant with previous history of malignancy is eligible, provided that there has been a disease-free interval for > 3 years
Has a known sensitivity to capecitabine, any of its components, or other drugs formulated with polysorbate 80
Has a known sensitivity to 5-fluorouracil (5-FU)
Has a known dihydropyrimidine dehydrogenase deficiency
Has received prior capecitabine treatment for advanced breast cancer
Has received investigational therapy within 2 weeks prior to randomization
Has received bevacizumab within 4 weeks prior to randomization
Has received more than 1 prior antiangiogenic agent for breast cancer
Has a known sensitivity to agents of similar biologic composition as ramucirumab DP or Icrucumab (IMC-18F1), or other agents that specifically target vascular endothelial growth factor (VEGF)
Has an acute/subacute bowel obstruction or history of chronic diarrhea requiring ongoing medical intervention
Has a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders
Has experienced a Grade ≥ 3 bleeding event within 3 months prior to randomization
Is receiving prophylactic or therapeutic anticoagulation with warfarin or any other oral anticoagulant
Has an uncontrolled intercurrent illness, including, but not limited to uncontrolled hypertension, symptomatic anemia, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorder in the opinion of the investigator
Has experienced any arterial thrombotic or thromboembolic events, including, but not limited to myocardial infarction, transient ischemic attack, or cerebrovascular accident within 6 months prior to randomization
Has brain metastases, uncontrolled spinal cord compression, or leptomeningeal disease
Has an ongoing or active infection requiring parenteral antibiotic, antifungal, or antiviral therapy
Has received a prior allogeneic organ or tissue transplantation
Has undergone major surgery within 4 weeks prior to randomization, or subcutaneous venous access device placement within 7 days prior to randomization
Has had a serious nonhealing wound, ulcer, or bone fracture within 4 weeks prior to randomization
Has known HIV or AIDS infection
Has an elective or planned major surgery to be performed during the course of the trial
Participant is pregnant or lactating