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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01427933
Recruitment Status : Completed
First Posted : September 2, 2011
Results First Posted : August 19, 2014
Last Update Posted : February 6, 2017
Information provided by (Responsible Party):
Eli Lilly and Company

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Breast Cancer Biological: Ramucirumab (IMC-1121B) Drug: Eribulin Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 141 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : November 2011
Actual Primary Completion Date : September 2013
Actual Study Completion Date : June 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

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 Name: 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

Primary Outcome Measures :
  1. Progression‐Free Survival (PFS) [ Time Frame: Start of treatment until documented disease progression or death from any cause up to 16.5 months ]
    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.

Secondary Outcome Measures :
  1. Overall Survival (OS) Randomization to Date of Death From Any Cause [ Time Frame: Randomization to date of death from any cause up to 28.6 months ]
    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.

  2. Objective Response Rate (ORR) Percentage of Participants With Measurable Disease Achieving a Best Overall Response of Partial Response (PR) or Complete Response (CR) [ Time Frame: Start of treatment until documented CR or PR up to 16.5 months ]
    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.

  3. Duration of Response (DOR) Time of Response to Progressive Disease [ Time Frame: Time from Observed CR or PR to PD up to 12.1 months ]
    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.

  4. Change in Tumor Size (CTS) [ Time Frame: Baseline, 6 weeks ]
    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.

  5. Number of Participants With Anti-Ramucirumab Antibodies [ Time Frame: Day 1 of Cycle 1, Cycle 3, Cycle 5 and 30 days after last dose of study drug up to 17.7 months ]
    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.

Other Outcome Measures:
  1. Number of Participants With Adverse Events (AE) and Participants Who Died [ Time Frame: Baseline up to end of treatment and within 30 days of last dose of study drug (22.6 months) ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01427933

  Hide Study Locations
United States, Alabama
ImClone Investigational Site
Birmingham, Alabama, United States, 35211
United States, California
ImClone Investigational Site
Gilroy, California, United States, 95020
ImClone Investigational Site
Palm Springs, California, United States, 92262
United States, Colorado
ImClone Investigational Site
Denver, Colorado, United States, 80220
United States, Connecticut
ImClone Investigational Site
Southington, Connecticut, United States, 06489
United States, Florida
ImClone Investigational Site
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
United States, Georgia
ImClone Investigational Site
Albany, Georgia, United States, 31701
ImClone Investigational Site
Lawrenceville, Georgia, United States, 30046
United States, Illinois
ImClone Investigational Site
Park Ridge, Illinois, United States, 60068
United States, Maryland
ImClone Investigational Site
Columbia, Maryland, United States, 21044
ImClone Investigational Site
Rockville, Maryland, United States, 20850
United States, Michigan
ImClone Investigational Site
Dearborn, Michigan, United States, 48126
United States, Minnesota
ImClone Investigational Site
Minneapolis, Minnesota, United States, 55404
United States, Missouri
ImClone Investigational Site
St Louis, Missouri, United States, 63110
ImClone Investigational Site
St. Joseph, Missouri, United States, 64507
United States, Nevada
ImClone Investigational Site
Henderson, Nevada, United States, 89074
United States, New Jersey
ImClone Investigational Site
Morristown, New Jersey, United States, 07960
United States, New York
ImClone Investigational Site
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
United States, North Carolina
ImClone Investigational Site
Burlington, North Carolina, United States, 27215
ImClone Investigational Site
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
ImClone Investigational Site
Dayton, Ohio, United States, 45429
ImClone Investigational Site
Middletown, Ohio, United States, 45042
ImClone Investigational Site
Toledo, Ohio, United States, 43623
United States, Oregon
ImClone Investigational Site
Portland, Oregon, United States, 97213
United States, Pennsylvania
ImClone Investigational Site
Pittsburgh, Pennsylvania, United States, 15213
United States, South Carolina
ImClone Investigational Site
Charleston, South Carolina, United States, 29414
ImClone Investigational Site
Greenville, South Carolina, United States, 29605
United States, Tennessee
ImClone Investigational Site
Chattanooga, Tennessee, United States, 37404
ImClone Investigational Site
Nashville, Tennessee, United States, 37203
United States, Texas
ImClone Investigational Site
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
United States, Vermont
ImClone Investigational Site
Rutland, Vermont, United States, 05701
United States, Virginia
ImClone Investigational Site
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
United States, Washington
ImClone Investigational Site
Vancouver, Washington, United States, 98684
Sponsors and Collaborators
Eli Lilly and Company
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company

Responsible Party: Eli Lilly and Company Identifier: NCT01427933     History of Changes
Other Study ID Numbers: 14392
I4T-IE-JVCD ( Other Identifier: Eli Lilly and Company )
CP12-1134 ( Other Identifier: Imclone Systems )
First Posted: September 2, 2011    Key Record Dates
Results First Posted: August 19, 2014
Last Update Posted: February 6, 2017
Last Verified: December 2016

Keywords provided by Eli Lilly and Company:
Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents