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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01427933
First received: August 31, 2011
Last updated: July 29, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
Breast Cancer
Biological: Ramucirumab (IMC-1121B)
Drug: Eribulin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Progression‐Free Survival (PFS) [ Time Frame: Start of treatment until documented disease progression or death from any cause up to 16.5 months ] [ Designated as safety issue: No ]
    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:
  • Overall Survival (OS) Randomization to Date of Death From Any Cause [ Time Frame: Randomization to date of death from any cause up to 24 months ] [ Designated as safety issue: Yes ]
    OS was defined as the time from the date of randomization to the date of death from any cause. 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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Change in Tumor Size (CTS) [ Time Frame: Baseline, 6 weeks ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: Yes ]
    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:
  • 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) ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 141
Study Start Date: November 2011
Study Completion Date: June 2014
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01427933

  Show 52 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01427933     History of Changes
Other Study ID Numbers: 14392, I4T-IE-JVCD, CP12-1134
Study First Received: August 31, 2011
Results First Received: July 29, 2014
Last Updated: July 29, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
Breast Cancer

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

ClinicalTrials.gov processed this record on October 23, 2014