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