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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01427933
• Other study ID #: 14392
• Secondary ID: I4T-IE-JVCDCP12-
• Status: Completed
• Phase: Phase 2
• First received: August 31, 2011
• Last updated: July 29, 2014
• Start date: November 2011
• Est. completion date: June 2014

Study information

• Verified date: July 2014
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 141
• Est. completion date: June 2014
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• Ramucirumab (IMC-1121B)
Administered intravenously

Drug:
• Eribulin
Administered intravenously

Locations

Country	Name	City	State
United States	ImClone Investigational Site	Albany	Georgia
United States	ImClone Investigational Site	Arlington	Texas
United States	ImClone Investigational Site	Bedford	Texas
United States	ImClone Investigational Site	Birmingham	Alabama
United States	ImClone Investigational Site	Bronx	New York
United States	ImClone Investigational Site	Burlington	North Carolina
United States	ImClone Investigational Site	Chapel Hill	North Carolina
United States	ImClone Investigational Site	Charleston	South Carolina
United States	ImClone Investigational Site	Chattanooga	Tennessee
United States	ImClone Investigational Site	Columbia	Maryland
United States	ImClone Investigational Site	Dallas	Texas
United States	ImClone Investigational Site	Dayton	Ohio
United States	ImClone Investigational Site	Dearborn	Michigan
United States	ImClone Investigational Site	Denver	Colorado
United States	ImClone Investigational Site	Fairfax	Virginia
United States	ImClone Investigational Site	Fort Myers	Florida
United States	ImClone Investigational Site	Fort Worth	Texas
United States	ImClone Investigational Site	Gilroy	California
United States	ImClone Investigational Site	Greenville	South Carolina
United States	ImClone Investigational Site	Henderson	Nevada
United States	ImClone Investigational Site	Houston	Texas
United States	ImClone Investigational Site	Jacksonville	Florida
United States	ImClone Investigational Site	Johnson City	New York
United States	ImClone Investigational Site	Lake Success	New York
United States	ImClone Investigational Site	Lawrenceville	Georgia
United States	ImClone Investigational Site	Middletown	Ohio
United States	ImClone Investigational Site	Minneapolis	Minnesota
United States	ImClone Investigational Site	Morristown	New Jersey
United States	ImClone Investigational Site	Nashville	Tennessee
United States	ImClone Investigational Site	Norfolk	Virginia
United States	ImClone Investigational Site	Orlando	Florida
United States	ImClone Investigational Site	Palm Springs	California
United States	ImClone Investigational Site	Park Ridge	Illinois
United States	ImClone Investigational Site	Pittsburgh	Pennsylvania
United States	ImClone Investigational Site	Plano	Texas
United States	ImClone Investigational Site	Plantation	Florida
United States	ImClone Investigational Site	Port St Lucie	Florida
United States	ImClone Investigational Site	Portland	Oregon
United States	ImClone Investigational Site	Richmond	Virginia
United States	ImClone Investigational Site	Rockville	Maryland
United States	ImClone Investigational Site	Rutland	Vermont
United States	ImClone Investigational Site	Salem	Virginia
United States	ImClone Investigational Site	San Antonio	Texas
United States	ImClone Investigational Site	Southington	Connecticut
United States	ImClone Investigational Site	St Louis	Missouri
United States	ImClone Investigational Site	St. Joseph	Missouri
United States	ImClone Investigational Site	St. Petersburg	Florida
United States	ImClone Investigational Site	Tampa	Florida
United States	ImClone Investigational Site	The Woodlands	Texas
United States	ImClone Investigational Site	Toledo	Ohio
United States	ImClone Investigational Site	Tyler	Texas
United States	ImClone Investigational Site	Vancouver	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)	Yes
Primary	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	No
Secondary	Overall Survival (OS) Randomization to Date of Death From Any Cause	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.	Randomization to date of death from any cause up to 24 months	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes