Phase III Study of Docetaxel + Ramucirumab or Placebo in Breast Cancer

Breast Cancer Clinical Trial

Official title:

A Multicenter, Multinational, Randomized, Double-Blind, Phase III Study of IMC-1121B Plus Docetaxel Versus Placebo Plus Docetaxel in Previously Untreated Patients With HER2-Negative, Unresectable, Locally-Recurrent or Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00703326
• Other study ID #: 13892
• Secondary ID: 2008-001727-65TR
• Status: Completed
• Phase: Phase 3
• Start date: August 6, 2008
• Est. completion date: November 19, 2020

Study information

• Verified date: November 2021
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to compare the progression-free survival (PFS) of the drug combination ramucirumab plus docetaxel to placebo plus docetaxel in previously untreated participants with human epidermal growth factor receptor 2 (HER2)-negative, unresectable, locally-recurrent or metastatic breast cancer.

Description:

Female participants at least 18 years of age with histologically or cytologically confirmed, human epidermal growth factor receptor 2 (HER2) negative breast adenocarcinoma that is metastatic or locally-recurrent and inoperable with curative intent will be randomized. Participants may not have received chemotherapy for metastatic or locally-recurrent, inoperable breast cancer. It is anticipated that 1113 participants will be randomized with 371 participants in the docetaxel plus placebo arm and 742 participants in the docetaxel plus ramucirumab (IMC-1121B) arm. There will be approximately 250 centers in North and South America, Europe, Asia, Middle East, Africa, Australia, and New Zealand. On Day 1 of each 21-day cycle, participants will receive docetaxel 75 mg/m² as a one-hour I.V. infusion followed by either ramucirumab (IMC-1121B) 10 mg/kg or placebo 10 mg/kg as a one-hour I.V. infusion. Each cycle is repeated every 21 days. Treatment will continue until there is evidence of progressive disease, unacceptable toxicity, or other withdrawal criteria are met. Participants who discontinue study treatment with either ramucirumab (IMC-1121B) or placebo may continue to receive docetaxel.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1144
• Est. completion date: November 19, 2020
• Est. primary completion date: March 31, 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participant is able to provide signed informed consent
• Participant is female and = 18 years of age or older if required by local laws or regulations
• Participant has histologically or cytologically confirmed adenocarcinoma of the breast that is now metastatic or locally-recurrent and inoperable with curative intent. Every effort should be made to make paraffin-embedded tissue or slides from the diagnostic biopsy or surgical specimen available for confirmation of diagnosis
• Participant has measurable and/or non-measurable disease
• Participants' primary and/or metastatic tumor is human epidermal growth factor receptor 2 (HER2)-negative by fluorescence in-situ hybridization (FISH) or chromogenic in-situ hybridization (CISH) or 0, 1+ overexpression by immunohistochemistry (IHC)
• Participant has not received prior chemotherapy for metastatic or locally-recurrent and inoperable breast cancer
• Participant completed (neo) adjuvant taxane therapy at least 6 months prior to randomization
• Participant completed (neo) adjuvant biologic therapy at least 6 weeks prior to randomization
• Participant completed all prior radiotherapy with curative intent = 3 weeks prior to randomization
• Participant may have received prior hormonal therapy for breast cancer in the (neo) adjuvant and/or the metastatic setting = 2 weeks prior to randomization
• Participant's left ventricular ejection fraction is within normal institutional ranges
• Participant has resolution to grade = 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3 (NCI-CTCAE v 3.0) of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy with the exception of peripheral neuropathy which must have resolved to grade = 2
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Participant is amenable to compliance with protocol schedules and testing
• Participant has adequate hematological functions [absolute neutrophil count (ANC) = 1500 cells/microliter (mcL), hemoglobin = 9 grams/deciliter (g/dL), and platelets = 100,000 cells/mcL and = 850,000 cells/mcL]
• Participant has adequate hepatic function [bilirubin within normal limits (WNL), aspartate transaminase (AST) and alanine transaminase (ALT) = 2.5 times the upper limit of normal (ULN), or = 5.0 times the ULN if the transaminase elevation is due to liver metastases, and alkaline phosphatase = 5.0 times the ULN]
• Participant has serum creatinine = 1.5 x ULN. If serum creatinine > 1.5 x ULN the calculated creatinine clearance should be > 40 milliliters/minute (mL/min)
• Participant's urinary protein is = 1+ on dipstick or routine urinalysis (UA); if urine protein = 2+, a 24-hour urine collection must demonstrate < 1000 milligrams (mg) of protein in 24 hours to allow participation in the study
• Participant must have adequate coagulation function as defined by international normalized ratio (INR) = 1.5 and a partial thromboplastin time (PTT) = 1.5 X ULN if not receiving anticoagulation therapy. Participants on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight heparin and if on warfarin must have a INR between 2 and 3 and have no active bleeding (defined as within 14 days of randomization) or pathological condition that carries a high risk of bleeding (such as, tumor involving major vessels or known varices)
• Women of childbearing potential must implement adequate contraception in the opinion of the investigator
• Participant has not received prior biologic therapy for metastatic or locally recurrent and inoperable breast cancer

Exclusion Criteria:

• Participant has a concurrent active malignancy other than breast adenocarcinoma, adequately treated non melanomatous skin cancer, or other non-invasive carcinoma or in situ neoplasm. A participant with previous history of malignancy is eligible, provided that she has been disease free for > 3 years
• Participant has a known sensitivity to docetaxel or other drugs formulated with polysorbate 80
• Participant has a known sensitivity to agents of similar biologic composition as ramucirumab or other agents that specifically target vascular endothelial growth factor (VEGF)
• Participant has a history of chronic diarrheal disease within 6 months prior to randomization
• Participant has received irradiation to a major bone marrow area as defined as > 25% of bone marrow (such as, pelvic or abdominal radiation) within 30 days prior to randomization
• Participant has participated in clinical trials of experimental agents within 4 weeks prior to randomization
• Participant has a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders
• Participant has active, high risk bleeding (such as, via gastric ulcers or gastric varices) within 14 days prior to randomization
• Participant has an ongoing or active infection requiring parenteral antibiotic, antifungal, or antiviral therapy
• Participant has uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorders in the opinion of the investigator
• Participant has brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease
• Participant has known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness
• Participant has pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
• Participant is pregnant or lactating

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• ramucirumab (IMC-1121B)
Ramucirumab (IMC-1121B) is administered at a dose of 10 milligrams per kilogram (mg/kg) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.

Drug:
• docetaxel
Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.

Other:
• Placebo
Placebo comparator for ramucirumab (IMC-1121B) administered at a dose of 10 mg/kg as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.

Locations

Country	Name	City	State
Australia	ImClone Investigational Site	Bankstown
Australia	ImClone Investigational Site	Bedford Park
Australia	ImClone Investigational Site	Box Hill
Australia	ImClone Investigational Site	Darlinghurst
Australia	ImClone Investigational Site	East Bentleigh
Australia	ImClone Investigational Site	East Melbourne
Australia	ImClone Investigational Site	Fitzroy	Victoria
Australia	ImClone Investigational Site	Frankston	Victoria
Australia	ImClone Investigational Site	Herston
Australia	ImClone Investigational Site	Hobart
Australia	ImClone Investigational Site	Milton
Australia	ImClone Investigational Site	Nambour
Australia	ImClone Investigational Site	New Lambton Heights
Australia	ImClone Investigational Site	Perth
Australia	ImClone Investigational Site	Ringwood East
Australia	ImClone Investigational Site	Subiaco
Australia	ImClone Investigational Site	Sydney
Australia	ImClone Investigational Site	Tweed Heads
Australia	ImClone Investigational Site	Wendouree
Belgium	ImClone Investigational Site	Brasschaat
Belgium	ImClone Investigational Site	Charleroi
Belgium	ImClone Investigational Site	Edegem
Belgium	ImClone Investigational Site	Gent
Belgium	ImClone Investigational Site	Kortrijk
Belgium	ImClone Investigational Site	Liege
Belgium	ImClone Investigational Site	Namur
Belgium	ImClone Investigational Site	Yvoir
Brazil	ImClone Investigational Site	Ijui
Brazil	ImClone Investigational Site	Porto Alegre
Brazil	ImClone Investigational Site	Porto Alegre
Brazil	ImClone Investigational Site	Porto Alegre
Brazil	ImClone Investigational Site	Rio de Janeiro
Brazil	ImClone Investigational Site	San Paulo
Brazil	ImClone Investigational Site	San Paulo
Brazil	ImClone Investigational Site	Santo Andre
Brazil	ImClone Investigational Site	Sao Paulo
Brazil	ImClone Investigational Site	Sao Paulo
Brazil	ImClone Investigational Site	Sao Paulo
Canada	ImClone Investigational Site	Calgary	Alberta
Canada	ImClone Investigational Site	Edmonton	Alberta
Canada	ImClone Investigational Site	Greenfield Park	Quebec
Canada	ImClone Investigational Site	Quebec
Canada	ImClone Investigational Site	Toronto	Ontario
Canada	ImClone Investigational Site	Vancouver	British Columbia
Canada	ImClone Investigational Site	Weston	Ontario
Croatia	ImClone Investigational Site	Osijek
Czechia	ImClone Investigational Site	Brno
Czechia	ImClone Investigational Site	Kutna Hora
Czechia	ImClone Investigational Site	Pardubice
Czechia	ImClone Investigational Site	Prague
Czechia	ImClone Investigational Site	Prague
Czechia	ImClone Investigational Site	Praha	Motol
Czechia	ImClone Investigational Site	Videnska
Egypt	ImClone Investigational Site	Alexandria
Egypt	ImClone Investigational Site	Cairo
Egypt	ImClone Investigational Site	Cairo
Germany	ImClone Investigational Site	Chemnitz
Germany	ImClone Investigational Site	Hamburg
Germany	ImClone Investigational Site	Hamburg
Germany	ImClone Investigational Site	Kiel
Germany	ImClone Investigational Site	Lubeck
Germany	ImClone Investigational Site	Munchen
Germany	ImClone Investigational Site	Munich
Germany	ImClone Investigational Site	Oldenburg
Germany	ImClone Investigational Site	Saarbrucken
Germany	ImClone Investigational Site	Trier
Germany	ImClone Investigational Site	Tubingen
Ireland	ImClone Investigational Site	Cork
Ireland	ImClone Investigational Site	Dublin
Ireland	ImClone Investigational Site	Dublin
Ireland	ImClone Investigational Site	Erlangen
Ireland	ImClone Investigational Site	Limerick
Israel	ImClone Investigational Site	Beersheva
Israel	ImClone Investigational Site	Jerusalem
Israel	ImClone Investigational Site	Petach-Tikva
Israel	ImClone Investigational Site	Rehovot
Israel	ImClone Investigational Site	Tel Aviv
Korea, Republic of	ImClone Investigational Site	Incheon
Korea, Republic of	ImClone Investigational Site	Seoul
Korea, Republic of	ImClone Investigational Site	Seoul
Korea, Republic of	ImClone Investigational Site	Seoul
Lebanon	ImClone Investigational Site	Beirut
Lebanon	ImClone Investigational Site	Bsalim
Lebanon	ImClone Investigational Site	Metn
Lebanon	ImClone Investigational Site	Saïda
Lebanon	ImClone Investigational Site	Zgharta
New Zealand	ImClone Investigational Site	Auckland
New Zealand	ImClone Investigational Site	Auckland
New Zealand	ImClone Investigational Site	Palmerston North
Peru	ImClone Investigational Site	Arequipa
Peru	ImClone Investigational Site	Lima
Peru	ImClone Investigational Site	Lima
Peru	ImClone Investigational Site	Lima
Peru	ImClone Investigational Site	Lima
Peru	ImClone Investigational Site	Lima
Poland	ImClone Investigational Site	Bytom
Poland	ImClone Investigational Site	Olsztyn
Poland	ImClone Investigational Site	Olsztyn
Russian Federation	ImClone Investigational Site	Engels
Russian Federation	ImClone Investigational Site	Kazan
Russian Federation	ImClone Investigational Site	Kursk
Russian Federation	ImClone Investigational Site	Leningrad Region
Russian Federation	ImClone Investigational Site	Lipetsk
Russian Federation	ImClone Investigational Site	Magnitogorsk
Russian Federation	ImClone Investigational Site	Moscow
Russian Federation	ImClone Investigational Site	Moscow
Russian Federation	ImClone Investigational Site	Moscow
Russian Federation	ImClone Investigational Site	Novosibirsk
Russian Federation	ImClone Investigational Site	Omsk
Russian Federation	ImClone Investigational Site	Orenburg
Russian Federation	ImClone Investigational Site	Perm
Russian Federation	ImClone Investigational Site	Samara
Russian Federation	ImClone Investigational Site	Saratov
Russian Federation	ImClone Investigational Site	St. Petersburg
Russian Federation	ImClone Investigational Site	St. Petersburg
Russian Federation	ImClone Investigational Site	Tambov
Russian Federation	ImClone Investigational Site	Ufa
Serbia	ImClone Investigational Site	Kragujevac
Serbia	ImClone Investigational Site	Nis
Serbia	ImClone Investigational Site	Sremska Kamenica
Slovakia	ImClone Investigational Site	Bratislava
Slovakia	ImClone Investigational Site	Trnava
Slovakia	ImClone Investigational Site	Zilina
South Africa	ImClone Investigational Site	Amanzimtoti
South Africa	ImClone Investigational Site	Bloemfontein
South Africa	ImClone Investigational Site	Durban
South Africa	ImClone Investigational Site	Durban
South Africa	ImClone Investigational Site	Lynnwood
South Africa	ImClone Investigational Site	Parktown	Johannesburg
South Africa	ImClone Investigational Site	Port Elizabeth
South Africa	ImClone Investigational Site	Pretoria
South Africa	ImClone Investigational Site	Pretoria
South Africa	ImClone Investigational Site	Pretoria
South Africa	ImClone Investigational Site	Sandton
Spain	ImClone Investigational Site	Alicante
Spain	ImClone Investigational Site	Badalona
Spain	ImClone Investigational Site	Barbastro
Spain	ImClone Investigational Site	Barcelona
Spain	ImClone Investigational Site	Barcelona
Spain	ImClone Investigational Site	Girona
Spain	ImClone Investigational Site	Jaen
Spain	ImClone Investigational Site	La Coruna
Spain	ImClone Investigational Site	La Laguna - Tenerife
Spain	ImClone Investigational Site	Lleida
Spain	ImClone Investigational Site	Madrid
Spain	ImClone Investigational Site	Madrid
Spain	ImClone Investigational Site	Madrid
Spain	ImClone Investigational Site	Madrid
Spain	ImClone Investigational Site	Madrid
Spain	ImClone Investigational Site	Malaga
Spain	ImClone Investigational Site	Palma de Mallorca
Spain	ImClone Investigational Site	Salamanca
Spain	ImClone Investigational Site	San Sebastian
Spain	ImClone Investigational Site	Santander
Spain	ImClone Investigational Site	Sevilla
Spain	ImClone Investigational Site	Toledo
Spain	ImClone Investigational Site	Valencia
Spain	ImClone Investigational Site	Valencia
Spain	ImClone Investigational Site	Zaragoza
Taiwan	ImClone Investigational Site	Changhua
Taiwan	ImClone Investigational Site	Taipei
Taiwan	ImClone Investigational Site	Taoyuan County
United Kingdom	ImClone Investigational Site	Bournemouth
United Kingdom	ImClone Investigational Site	Edinburgh
United Kingdom	ImClone Investigational Site	Huddersfield
United Kingdom	ImClone Investigational Site	Hull
United Kingdom	ImClone Investigational Site	Manchester
United Kingdom	ImClone Investigational Site	Nottingham
United States	ImClone Investigational Site	Alhambra	California
United States	ImClone Investigational Site	Alton	Illinois
United States	ImClone Investigational Site	Atlanta	Georgia
United States	ImClone Investigational Site	Atlanta	Georgia
United States	ImClone Investigational Site	Aurora	Colorado
United States	ImClone Investigational Site	Bakersfield	California
United States	ImClone Investigational Site	Bartlett	Tennessee
United States	ImClone Investigational Site	Birmingham	Alabama
United States	ImClone Investigational Site	Bismarck	North Dakota
United States	ImClone Investigational Site	Chandler	Arizona
United States	ImClone Investigational Site	Charlotte	North Carolina
United States	ImClone Investigational Site	Charlotte	North Carolina
United States	ImClone Investigational Site	Charlotte	North Carolina
United States	ImClone Investigational Site	Charlotte	North Carolina
United States	ImClone Investigational Site	Charlotte	North Carolina
United States	ImClone Investigational Site	Charlotte	North Carolina
United States	ImClone Investigational Site	Chicago	Illinois
United States	ImClone Investigational Site	Chicago	Illinois
United States	ImClone Investigational Site	Chula Vista	California
United States	ImClone Investigational Site	Elkhart	Indiana
United States	ImClone Investigational Site	Fort Lauderdale	Florida
United States	ImClone Investigational Site	Gainesville	Florida
United States	ImClone Investigational Site	Germantown	Tennessee
United States	ImClone Investigational Site	Gilbert	Arizona
United States	ImClone Investigational Site	Grand Island	Nebraska
United States	ImClone Investigational Site	Henderson	Nevada
United States	ImClone Investigational Site	Kearney	Nebraska
United States	ImClone Investigational Site	La Mesa	California
United States	ImClone Investigational Site	Lansing	Michigan
United States	ImClone Investigational Site	Lexington	Kentucky
United States	ImClone Investigational Site	Los Angeles	California
United States	ImClone Investigational Site	Lubbock	Texas
United States	ImClone Investigational Site	Macon	Georgia
United States	ImClone Investigational Site	Marietta	Georgia
United States	ImClone Investigational Site	Memphis	Tennessee
United States	ImClone Investigational Site	Memphis	Tennessee
United States	ImClone Investigational Site	Memphis	Tennessee
United States	ImClone Investigational Site	Mesa	Arizona
United States	ImClone Investigational Site	Minneapolis	Minnesota
United States	ImClone Investigational Site	Mishawaka	Indiana
United States	ImClone Investigational Site	Mobile	Alabama
United States	ImClone Investigational Site	New Port Richey	Florida
United States	ImClone Investigational Site	New York	New York
United States	ImClone Investigational Site	Niles	Tennessee
United States	ImClone Investigational Site	Oceanside	California
United States	ImClone Investigational Site	Oklahoma City	Oklahoma
United States	ImClone Investigational Site	Oxford	Tennessee
United States	ImClone Investigational Site	Pasadena	California
United States	ImClone Investigational Site	Pasadena	California
United States	ImClone Investigational Site	Portland	Oregon
United States	ImClone Investigational Site	Saint Joseph	Michigan
United States	ImClone Investigational Site	Saint Louis	Missouri
United States	ImClone Investigational Site	Salt Lake City	Utah
United States	ImClone Investigational Site	San Diego	California
United States	ImClone Investigational Site	Santa Barbara	California
United States	ImClone Investigational Site	Santa Maria	California
United States	ImClone Investigational Site	Santa Monica	California
United States	ImClone Investigational Site	Skokie	Illinois
United States	ImClone Investigational Site	Solvang	California
United States	ImClone Investigational Site	South Bend	Indiana
United States	ImClone Investigational Site	Southaven	Mississippi
United States	ImClone Investigational Site	Temple	Texas
United States	ImClone Investigational Site	Valencia	California
United States	ImClone Investigational Site	West Reading	Pennsylvania
United States	ImClone Investigational Site	Westville	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  Croatia,  Czechia,  Egypt,  Germany,  Ireland,  Israel,  Korea, Republic of,  Lebanon,  New Zealand,  Peru,  Poland,  Russian Federation,  Serbia,  Slovakia,  South Africa,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS)	PFS was defined as time from randomization until the first evidence of progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.0) or death from any cause; by Investigator assessment. Progressive disease (PD) was defined as at least a 20% increase in sum of longest diameter of target lesions taking as reference the smallest sum longest diameter since baseline, progression in non-target lesions or the appearance of 1 or more new lesion(s). Participants who neither progressed nor died were censored the day of their last radiographic tumor assessment if available or date of randomization if no post initiation radiographic assessment was available. If death or PD occurred after =2 missing radiographic visits, censoring occurred at date of the last radiographic visit prior to the missed visits. The symptomatic/clinical disease progression (deterioration) without documented radiologic progression did not constitute progression.	Randomization to disease progression or death or until data cutoff of 31 Mar 2013 (up to 56 months)
Secondary	Overall Survival (OS)	OS was defined as the duration from randomization to death from any cause. Participants who were alive at data cut-off for the OS analysis or lost to follow-up were censored on the last date the participant was known to be alive.	Randomization to death or until data cutoff of 29-May-2015 (up to 82 months)
Secondary	Time to Progression (TTP)	TTP was defined as the time from the date of randomization to the first documented date of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria; by Investigator assessment. Progressive disease (PD) was defined as at least a 20% increase in sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD since baseline, progression in non-target lesions or the appearance of 1 or more new lesion(s). Participants who did not progress were censored at the last radiographic tumor assessment. If no post-baseline assessment was available censoring occurred at the date of randomization. If PD occurred after 2 or more missing radiographic visits, censoring occurred at the date of the last radiographic visit prior to the missed visits. The symptomatic/clinical disease progression (deterioration) without documented radiologic progression did not constitute progression.	Randomization to disease progression or until data cutoff of 31-Mar-2013 (up to 56 months)
Secondary	Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate)	Objective response rate (ORR) was defined as the percentage of randomized participants achieving a best confirmed overall response of CR or PR using Response Evaluation Criteria in Solid Tumors (RECIST v1.0), based on the achievement of both measurement and confirmation criteria; by Investigator assessment. CR was defined as the disappearance of all target and non-target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions, taking as reference the baseline sum LD and no progression in non-target lesions.	Randomization to disease progression or until data cutoff of 31-Mar-2013 (up to 56 months)
Secondary	Duration of Response	Duration of complete response (CR) or partial response (PR) measured from time criteria were first met for CR or PR until first date of progressive disease (PD) or death from any cause defined using Response Evaluation Criteria in Solid Tumor (RECIST 1.0); by Investigator assessment. CR defined as disappearance of all target and non-target lesions. PR defined as =30% decrease in sum of longest diameter (LD) of target lesions and no progression in non-target lesions. PD defined as =20% increase in LD sum of target lesions taking as reference the smallest sum LD since baseline, progression in non-target lesions or the appearance of =1 new lesion(s). Participants who did not relapse or die censored at day of last radiographic tumor assessment. If death or PD was after =2 missing radiographic visits, censoring was at date of last radiographic visit prior to missed visits. Symptomatic/clinical disease progression without documented radiologic progression did not constitute progression.	Date of first CR or PR to PD or death or until data cutoff date of 31-Mar-2013 (up to 56 months)
Secondary	Total Functional Assessment of Cancer Therapy-Breast (FACT-B): Change From Baseline to End of Therapy	FACT-B measures the following domains of health-related quality of life (HR-QoL): physical well-being (PWB), social/family well-being (SFWB), emotional well-being (EWB), functional well-being (FWB), and additional concerns of breast cancer subscale (BCS) each with 6 or more items developed to measure problems specific to breast cancer symptoms plus additional items related to global QoL. Participants respond to each of the 36 questions on a 5-point scale from 0 (not at all) to 4 (very much) with a total scores range of 0-144. Higher scores indicate fewer symptoms and better HR-QoL.	Baseline, End of Therapy or until data cutoff of 31-Mar-2013 (up to 56 months)
Secondary	Number of Participants With Adverse Events	Clinically significant events were defined as serious adverse events (SAE) and other treatment-emergent non-serious adverse events (NSAE). A summary of SAEs and other NSAEs is located in the Reported Adverse Event module.	First dose to study completion (up to 12.3 years)
Secondary	Immunogenicity: Percentage of Participants With Treatment Emergent Anti-Ramucirumab Antibodies Until Primary Data Cutoff of 31-Mar-2013	Percentage of participants with treatment-emergent positive for anti-ramucirumab (IMC-1121B) antibodies during the study. Participants were considered positive for anti-ramucirumab (IMC-1121B) antibodies if they exhibited a post-treatment antibody level that exceeded the positive upper cut point determined from the anti-ramucirumab (IMC-1121B) level seen in healthy untreated individuals.	Baseline, prior to cycle 3 infusion, prior to cycle 5 infusion, onset of infusion reaction, resolution of reaction and 30 days following the event up to 56 months
Secondary	Immunogenicity: Percentage of Participants Available After 31-Mar-2013 With Treatment Emergent Anti-Ramucirumab Antibodies Until Data Cutoff From 01-Apr-2013 to 08-Sep-2016	Percentage of participants with treatment-emergent positive for anti-ramucirumab (IMC-1121B) antibodies during the study. Participants were considered positive for anti-ramucirumab (IMC-1121B) antibodies if they exhibited a post-treatment antibody level that exceeded the positive upper cut point determined from the anti-ramucirumab (IMC-1121B) level seen in healthy untreated individuals.	Follow-up from 01-Apr-2013 to 08-Sep-2016 (Up to 56 -97 months)