A Study of Ramucirumab (IMC-1121B) in Combination With Eribulin Versus Eribulin Alone in Participants With Breast Cancer

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

This is a study to compare the antitumor activity of ramucirumab (IMC-1121B) and eribulin together versus eribulin alone, in participants with locally recurrent or metastatic breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Biological: Ramucirumab (IMC-1121B); Drug: Eribulin

• Study Type: Interventional
• Enrollment (Actual): 141
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • ImClone Investigational Site
  • California
    • Gilroy, California, United States, 95020
      • ImClone Investigational Site
    • Palm Springs, California, United States, 92262
      • ImClone Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80220
      • ImClone Investigational Site
  • Connecticut
    • Southington, Connecticut, United States, 06489
      • ImClone Investigational Site
  • Florida
    • Fort Myers, Florida, United States, 33916
      • ImClone Investigational Site
    • Jacksonville, Florida, United States, 32207
      • ImClone Investigational Site
    • Orlando, Florida, United States, 32806
      • ImClone Investigational Site
    • Plantation, Florida, United States, 33324
      • ImClone Investigational Site
    • Port St Lucie, Florida, United States, 34952
      • ImClone Investigational Site
    • St. Petersburg, Florida, United States, 33705
      • ImClone Investigational Site
    • Tampa, Florida, United States, 33612
      • ImClone Investigational Site
  • Georgia
    • Albany, Georgia, United States, 31701
      • ImClone Investigational Site
    • Lawrenceville, Georgia, United States, 30046
      • ImClone Investigational Site
  • Illinois
    • Park Ridge, Illinois, United States, 60068
      • ImClone Investigational Site
  • Maryland
    • Columbia, Maryland, United States, 21044
      • ImClone Investigational Site
    • Rockville, Maryland, United States, 20850
      • ImClone Investigational Site
  • Michigan
    • Dearborn, Michigan, United States, 48126
      • ImClone Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • ImClone Investigational Site
  • Missouri
    • St Louis, Missouri, United States, 63110
      • ImClone Investigational Site
    • St. Joseph, Missouri, United States, 64507
      • ImClone Investigational Site
  • Nevada
    • Henderson, Nevada, United States, 89074
      • ImClone Investigational Site
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • ImClone Investigational Site
  • New York
    • Bronx, New York, United States, 10469
      • ImClone Investigational Site
    • Johnson City, New York, United States, 13790
      • ImClone Investigational Site
    • Lake Success, New York, United States, 11042
      • ImClone Investigational Site
  • North Carolina
    • Burlington, North Carolina, United States, 27215
      • ImClone Investigational Site
    • Chapel Hill, North Carolina, United States, 27599
      • ImClone Investigational Site
  • Ohio
    • Dayton, Ohio, United States, 45429
      • ImClone Investigational Site
    • Middletown, Ohio, United States, 45042
      • ImClone Investigational Site
    • Toledo, Ohio, United States, 43623
      • ImClone Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97213
      • ImClone Investigational Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • ImClone Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • ImClone Investigational Site
    • Greenville, South Carolina, United States, 29605
      • ImClone Investigational Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • ImClone Investigational Site
    • Nashville, Tennessee, United States, 37203
      • ImClone Investigational Site
  • Texas
    • Arlington, Texas, United States, 76014
      • ImClone Investigational Site
    • Bedford, Texas, United States, 76022
      • ImClone Investigational Site
    • Dallas, Texas, United States, 75246
      • ImClone Investigational Site
    • Fort Worth, Texas, United States, 76104
      • ImClone Investigational Site
    • Houston, Texas, United States, 77024
      • ImClone Investigational Site
    • Plano, Texas, United States, 75075
      • ImClone Investigational Site
    • San Antonio, Texas, United States, 78217
      • ImClone Investigational Site
    • The Woodlands, Texas, United States, 77380
      • ImClone Investigational Site
    • Tyler, Texas, United States, 75702
      • ImClone Investigational Site
  • Vermont
    • Rutland, Vermont, United States, 05701
      • ImClone Investigational Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • ImClone Investigational Site
    • Norfolk, Virginia, United States, 23502
      • ImClone Investigational Site
    • Richmond, Virginia, United States, 23230
      • ImClone Investigational Site
    • Salem, Virginia, United States, 24153
      • ImClone Investigational Site
  • Washington
    • Vancouver, Washington, United States, 98684
      • ImClone Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 version 1.1 (RECIST v1.1)
• 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 Human Epidermal Growth Factor Receptor 2 (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 de 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ramucirumab and Eribulin; Ramucirumab 10 milligrams/kilogram (mg/kg) administered by intravenous (IV) infusion on Day 1 of each 3-week cycle Eribulin 1.4 milligrams/square meter (mg/m²) administered by IV bolus on Day 1 and Day 8 of each 3-week cycle	Biological: Ramucirumab (IMC-1121B); Administered intravenously; Other Names: LY3009806; Drug: Eribulin; Administered intravenously
ACTIVE_COMPARATOR: Eribulin Monotherapy; Eribulin 1.4 mg/m² administered by IV bolus on Day 1 and Day 8 of each 3-week cycle	Drug: Eribulin; Administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS was defined as time from date of randomization until the date of objectively determined progression defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria or death from any cause, whichever is first. Progressive disease (PD) defined as ≥20% increase in sum of diameter (SOD) of target lesion with the sum demonstrating an increase of ≥5 mm; appearance of ≥1 new lesions or unequivocal progression of non-target lesions. Participants with no baseline disease assessment were censored at randomization date, regardless of whether or not objectively determined PD or death was observed; participants not known to have died or to have objective progression as of data inclusion cutoff date were censored at last post baseline radiological assessment date or randomization date, if there was no post baseline radiological assessment.	Start of treatment until documented disease progression or death from any cause up to 16.5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) Randomization to Date of Death From Any Cause	Time from the date of randomization to the date of death from any cause. For participants who were not known to have died as of the data-inclusion cut-off date, OS data were censored on the last date the participants were known to be alive prior to that cut-off date.	Randomization to date of death from any cause up to 28.6 months
Objective Response Rate (ORR) Percentage of Participants With Measurable Disease Achieving a Best Overall Response of Partial Response (PR) or Complete Response (CR)	ORR was defined as the percentage of participants with measurable disease achieving a best overall response of PR or CR as defined by RECIST v.1.1. CR defined as disappearance of all lesions and pathological lymph nodes reduction in short axis to <10 mm. PR was defined as ≥30% decrease in SOD of target lesions. Participants who did not have any post baseline tumor response assessments for any reason were considered non-responders and included in the denominator when calculating the response rate. ORR for each treatment arm calculated as: [(CR + PR in the treatment arm) divided by (total number of participants in the treatment arm)] x 100.	Start of treatment until documented CR or PR up to 16.5 months
Duration of Response (DOR) Time of Response to Progressive Disease	DOR was measured from the time criteria were met for first objectively recorded CR or PR until first date criteria for PD was met or death. Response defined using RECIST v1.1 criteria. CR defined as disappearance of all lesions and pathological lymph nodes reduction in short axis to <10 mm. PR was defined as ≥30% decrease in sum of diameter (SOD) of target lesions. PD defined ≥20% increase in SOD of target lesion with the sum demonstrating an increase of ≥5 mm; appearance of ≥1 new lesions or unequivocal progression of non-target lesions. Participants who were not known to have died and who did not have PD were censored at the date of the last tumor assessment prior to the date of any subsequent systemic anticancer therapy.	Time from Observed CR or PR to PD up to 12.1 months
Change in Tumor Size (CTS)	CTS was defines as the change from baseline measurement of target lesions to the post treatment measurement in participants with measurable disease. Change was assessed using radiographic imagining. Log ratio calculated as: log of (tumor size post baseline) divided by (tumor size at baseline). A negative result indicated a shrinking tumor.	Baseline, 6 weeks
Number of Participants With Anti-Ramucirumab Antibodies	The number of participants who developed treatment-emergent antibody responses after baseline. The antibody test can produce positive results in participants without ramucirumab exposure. Treatment emergent anti-ramucirumab antibody positive was defined as: when baseline titer was greater than 0 and post baseline titer was equal to or greater than 4-fold the baseline titer or if the baseline titer was not detected and post baseline titer is equal to or greater than a value of 20.	Day 1 of Cycle 1, Cycle 3, Cycle 5 and 30 days after last dose of study drug up to 17.7 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AE) and Participants Who Died	Participants who died or who had clinically significant events defined as serious AEs (SAEs) and other non-serious AEs (regardless of causality). A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.	Baseline up to end of treatment and within 30 days of last dose of study drug (22.6 months)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (ACTUAL): September 1, 2013
• Study Completion (ACTUAL): June 1, 2014

Study Registration Dates

• First Submitted: August 31, 2011
• First Submitted That Met QC Criteria: September 1, 2011
• First Posted (ESTIMATE): September 2, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): February 6, 2017
• Last Update Submitted That Met QC Criteria: December 9, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Breast Cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Ramucirumab
• Other Study ID Numbers: 14392; I4T-IE-JVCD (OTHER: Eli Lilly and Company); CP12-1134 (OTHER: Imclone Systems)