An Open-Label, Multicenter, Randomized, Phase 2 Study Evaluating the Efficacy and Safety of Ramucirumab (IMC-1121B) Drug Product in Combination With Eribulin Versus Eribulin Monotherapy in Unresectable, Locally-Recurrent or Metastatic Breast Cancer Patients Previously Treated With Anthracycline and Taxane Therapy
Inclusion Criteria:
- Have histologically or cytologically confirmed invasive breast cancer which at the
time of study entry is either locally-recurrent disease not amenable to curative
therapy or Stage IV disease (American Joint Committee on Cancer Staging Criteria for
breast cancer)
- Have measurable and/or nonmeasurable disease per Response Evaluation Criteria in
Solid Tumors (RECIST 1.1)
- Have received at least 2 but not more than 4 prior cytotoxic chemotherapy regimens in
the locally recurrent or metastatic setting
- Have received prior treatment with both anthracyclines and taxanes, either in the
metastatic, adjuvant or neoadjuvant setting
- Have received HER-2-directed treatment; or are not a candidate for HER-2-directed
treatment if the patient has HER-2 positive disease
- Have completed any prior radiotherapy and/or hormonal therapy at least 1 week prior
to randomization and have recovered from all clinically significant treatment-related
toxicities
- Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Have left ventricular ejection fraction within normal limits
- Have discontinued all previous chemotherapy treatments for cancer at least 3 weeks
prior to randomization and recovered from clinically significant toxic effects
- Have resolution to Grade less than or equal to 1 [by the National Cancer Institute -
Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0] of all
clinically significant toxicities of prior chemotherapy, surgery, radiotherapy, or
hormonal therapy with the exception of peripheral neuropathy, which must have
resolved to Grade less than or equal to 2
- Have adequate hematologic, hepatic, renal, and coagulation function
- Test negative for pregnancy
- Have a life expectancy of at least 3 months
Exclusion Criteria:
- Have a concurrent active other malignancy other than adequately treated
non-melanomatous skin cancer or other noninvasive or in situ neoplasms
- Are currently enrolled in, or recently discontinued from, a clinical trial involving
an investigational product, or concurrently enrolled in any other type of medical
research judged not to be medically compatible with the study
- Have received investigational therapy within 3 weeks prior to randomization
- Have received prior ramucirumab or eribulin
- Have a known sensitivity to agents of similar biologic composition as ramucirumab,
halichondrin B and/or halichondrin B chemical derivative
- Have received bevacizumab within 6 weeks prior to randomization
- Have uncontrolled or poorly controlled hypertension
- Have congenital prolonged QTc syndrome (or have a family history)or prolongation of
QTc at baseline
- Have a history of additional risk factors for Torsades des pointes within the last
year prior to randomization
- Have an implantable pacemaker or automatic implantable cardioverter defibrillator
- Have bradycardia
- Have an acute/subacute bowel obstruction or history of chronic diarrhea requiring
ongoing medical intervention within 6 months prior to randomization
- Have a history of uncontrolled hereditary or acquired bleeding or thrombotic
disorders
- Have experienced a Grade 3 or greater bleeding event within 3 months prior to
randomization
- Have experienced any Grade 3 or greater arterial thromboembolic events within 6
months prior to randomization, or venous thromboembolic event within 3 months prior
to randomization
- Have undergone major surgery within 4 weeks prior to randomization or subcutaneous
venous access device placement within 7 days prior to randomization
- Have a planned major surgery to be performed during the course of the trial
- Have uncontrolled metabolic conditions
- Have an ongoing or active infection requiring parenteral antibiotic, antifungal, or
antiviral therapy
- Have known human immunodeficiency virus (HIV) infection or acquired immunodeficiency
syndrome (AIDS)
- Have pulmonary lymphangitic involvement that results in pulmonary dysfunction
requiring active treatment including the use of oxygen
- Have received a prior allogeneic organ or tissue transplantation
- Have had a serious nonhealing wound, ulcer, or bone fracture within 4 weeks prior to
randomization
- Have known leptomeningeal metastases
- Have cirrhosis (Child-Pugh Level B or worse) or cirrhosis (any degree) and a history
of hepatic encephalopathy or clinically meaningful ascites