Clinical trial NCT01427933: A Study of Ramucirumab (IMC-1121B) in Combination With Eribulin Versus Eribulin Alone in Participants With Breast Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Breast Cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2011-09-02
Enrollment: 141
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Start of treatment until documented disease progression or death from any cause up to 16.5 months
Secondary outcomes:
measure: Overall Survival (OS) Randomization to Date of Death From Any Cause
timeFrame: Randomization to date of death from any cause up to 28.6 months
measure: Objective Response Rate (ORR) Percentage of Participants With Measurable Disease Achieving a Best Overall Response of Partial Response (PR) or Complete Response (CR)
timeFrame: Start of treatment until documented CR or PR up to 16.5 months
measure: Duration of Response (DOR) Time of Response to Progressive Disease
timeFrame: Time from Observed CR or PR to PD up to 12.1 months
measure: Change in Tumor Size (CTS)
timeFrame: Baseline, 6 weeks
measure: Number of Participants With Anti-Ramucirumab Antibodies
timeFrame: Day 1 of Cycle 1, Cycle 3, Cycle 5 and 30 days after last dose of study drug up to 17.7 months
Other outcomes:
measure: Number of Participants With Adverse Events (AE) and Participants Who Died
timeFrame: Baseline up to end of treatment and within 30 days of last dose of study drug (22.6 months)
Locations:
city: Birmingham
country: United States
facility: ImClone Investigational Site
state: Alabama
city: Gilroy
country: United States
facility: ImClone Investigational Site
state: California
city: Palm Springs
country: United States
facility: ImClone Investigational Site
state: California
city: Denver
country: United States
facility: ImClone Investigational Site
state: Colorado
city: Southington
country: United States
facility: ImClone Investigational Site
state: Connecticut
city: Fort Myers
country: United States
facility: ImClone Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: ImClone Investigational Site
state: Florida
city: Orlando
country: United States
facility: ImClone Investigational Site
state: Florida
city: Plantation
country: United States
facility: ImClone Investigational Site
state: Florida
city: Port St Lucie
country: United States
facility: ImClone Investigational Site
state: Florida
city: St. Petersburg
country: United States
facility: ImClone Investigational Site
state: Florida
city: Tampa
country: United States
facility: ImClone Investigational Site
state: Florida
city: Albany
country: United States
facility: ImClone Investigational Site
state: Georgia
city: Lawrenceville
country: United States
facility: ImClone Investigational Site
state: Georgia
city: Park Ridge
country: United States
facility: ImClone Investigational Site
state: Illinois
city: Columbia
country: United States
facility: ImClone Investigational Site
state: Maryland
city: Rockville
country: United States
facility: ImClone Investigational Site
state: Maryland
city: Dearborn
country: United States
facility: ImClone Investigational Site
state: Michigan
city: Minneapolis
country: United States
facility: ImClone Investigational Site
state: Minnesota
city: St Louis
country: United States
facility: ImClone Investigational Site
state: Missouri
city: St. Joseph
country: United States
facility: ImClone Investigational Site
state: Missouri
city: Henderson
country: United States
facility: ImClone Investigational Site
state: Nevada
city: Morristown
country: United States
facility: ImClone Investigational Site
state: New Jersey
city: Bronx
country: United States
facility: ImClone Investigational Site
state: New York
city: Johnson City
country: United States
facility: ImClone Investigational Site
state: New York
city: Lake Success
country: United States
facility: ImClone Investigational Site
state: New York
city: Burlington
country: United States
facility: ImClone Investigational Site
state: North Carolina
city: Chapel Hill
country: United States
facility: ImClone Investigational Site
state: North Carolina
city: Dayton
country: United States
facility: ImClone Investigational Site
state: Ohio
city: Middletown
country: United States
facility: ImClone Investigational Site
state: Ohio
city: Toledo
country: United States
facility: ImClone Investigational Site
state: Ohio
city: Portland
country: United States
facility: ImClone Investigational Site
state: Oregon
city: Pittsburgh
country: United States
facility: ImClone Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: ImClone Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: ImClone Investigational Site
state: South Carolina
city: Chattanooga
country: United States
facility: ImClone Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: ImClone Investigational Site
state: Tennessee
city: Arlington
country: United States
facility: ImClone Investigational Site
state: Texas
city: Bedford
country: United States
facility: ImClone Investigational Site
state: Texas
city: Dallas
country: United States
facility: ImClone Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: ImClone Investigational Site
state: Texas
city: Houston
country: United States
facility: ImClone Investigational Site
state: Texas
city: Plano
country: United States
facility: ImClone Investigational Site
state: Texas
city: San Antonio
country: United States
facility: ImClone Investigational Site
state: Texas
city: The Woodlands
country: United States
facility: ImClone Investigational Site
state: Texas
city: Tyler
country: United States
facility: ImClone Investigational Site
state: Texas
city: Rutland
country: United States
facility: ImClone Investigational Site
state: Vermont
city: Fairfax
country: United States
facility: ImClone Investigational Site
state: Virginia
city: Norfolk
country: United States
facility: ImClone Investigational Site
state: Virginia
city: Richmond
country: United States
facility: ImClone Investigational Site
state: Virginia
city: Salem
country: United States
facility: ImClone Investigational Site
state: Virginia
city: Vancouver
country: United States
facility: ImClone Investigational Site
state: Washington
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: