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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

Phase 3
18 Years
Open (Enrolling)
Breast Cancer

Thank you

Trial Information

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

Female patients 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.
Patients may not have received chemotherapy for metastatic or locally-recurrent, inoperable
breast cancer.

It is anticipated that 1113 patients will be randomized with 371 patients in the docetaxel
plus placebo arm and 742 patients in the docetaxel plus IMC ramucirumab 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, patients will receive docetaxel 75 mg/m2 as a one-hour I.V.
infusion followed by either IMC ramucirumab 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. Patients who discontinue study treatment
with either ramucirumab or placebo may continue to receive docetaxel. Similarly, patients
who discontinue docetaxel therapy may continue to receive either ramucirumab or placebo,
whichever the patient was randomized to receive. All patients will be followed for survival
at regularly scheduled intervals (every 6 weeks until progressive disease and every 6 months
thereafter) for at least 36 months after discontinuing study therapy.

Inclusion Criteria:

- Patient is able to provide signed informed consent

- Patient is female and ≥ 18 years of age or older if required by local laws or

- Patient 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

- Patient has measurable and/or non-measurable disease

- Patients' primary and/or metastatic tumor is HER2-negative by fluorescence in-situ
hybridization (FISH) or chromogenic in-situ hybridization (CISH) or 0, 1+
overexpression by immunohistochemistry (IHC)

- Patient has not received prior chemotherapy for metastatic or locally-recurrent and
inoperable breast cancer

- Patient completed (neo) adjuvant taxane therapy at least 6 months prior to

- Patient completed (neo) adjuvant biologic therapy at least 6 weeks prior to

- Patient completed all prior radiotherapy with curative intent ≥ 3 weeks prior to

- Patient may have received prior hormonal therapy for breast cancer in the (neo)
adjuvant and/or the metastatic setting ≥ 2 weeks prior to randomization

- Patient's left ventricular ejection fraction is within normal institutional ranges

- Patient 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

- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

- Patient is amenable to compliance with protocol schedules and testing

- Patient has adequate hematological functions (absolute neutrophil count [ANC] ≥ 1500
cells/uL, hemoglobin ≥ 9 g/dL, and platelets ≥ 100,000 cells/uL and ≤ 850,000

- Patient 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)

- Patient has serum creatinine ≤ 1.5 x ULN. If serum creatinine > 1.5 x ULN the
calculated creatinine clearance should be > 40 mL/min)

- Patient's urinary protein is ≤ 1+ on dipstick or routine urinalysis (UA); if urine
protein ≥ 2+, a 24-hour urine collection must demonstrate < 1000 mg of protein in 24
hours to allow participation in the study

- Patient 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. Patients 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 (eg, tumor involving major vessels or known varices)

- Women of childbearing potential must implement adequate contraception in the opinion
of the investigator

- Patient has not received prior biologic therapy for metastatic or locally recurrent
and inoperable breast cancer

Exclusion Criteria:

- Patient 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 patient with previous history of malignancy is eligible,
provided that she has been disease free for > 3 years

- Patient has a known sensitivity to docetaxel or other drugs formulated with
polysorbate 80

- Patient has a known sensitivity to agents of similar biologic composition as
ramucirumab or other agents that specifically target VEGF

- Patient has a history of chronic diarrheal disease within 6 months prior to

- Patient has received irradiation to a major bone marrow area as defined as > 25% of
bone marrow (eg, pelvic or abdominal radiation) within 30 days prior to randomization

- Patient has participated in clinical trials of experimental agents within 4 weeks
prior to randomization

- Patient has a history of uncontrolled hereditary or acquired bleeding or thrombotic

- Patient has active, high risk bleeding (eg, via gastric ulcers or gastric varices)
within 14 days prior to randomization

- Patient has an ongoing or active infection requiring parenteral antibiotic,
antifungal, or antiviral therapy

- Patient 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

- Patient has brain metastases, uncontrolled spinal cord compression, or carcinomatous
meningitis, or new evidence of brain or leptomeningeal disease

- Patient has known human immunodeficiency virus infection or acquired immunodeficiency
syndrome-related illness

- Patient has pulmonary lymphangitic involvement that results in pulmonary dysfunction
requiring active treatment, including the use of oxygen.

- Patient is pregnant or lactating

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

Progression-Free Survival (PFS)

Outcome Description:

Progression-free survival (PFS) is measured from the date of randomization to the first documented date of disease progression or death from any cause.

Outcome Time Frame:

up to 36 months

Safety Issue:


Principal Investigator

E-mail: ClinicalTrials@

Investigator Role:

Study Director

Investigator Affiliation:

ImClone LLC


Belgium: Federal Agency for Medicinal Products and Health Products

Study ID:




Start Date:

August 2008

Completion Date:

December 2015

Related Keywords:

  • Breast Cancer
  • Metastatic breast cancer
  • HER2 negative breast cancer
  • locally recurrent breast cancer
  • Breast Neoplasms



ImClone Investigational Site Denver, Colorado  80262
ImClone Investigational Site Indianapolis, Indiana  46202
ImClone Investigational Site New York, New York  10021
ImClone Investigational Site St. Charles, Missouri  63301
ImClone Investigational Site Bakersfield, California  93309
ImClone Investigational Site Jacksonville, Florida  32207
ImClone Investigational Site Atlanta, Georgia  30318
ImClone Investigational Site Decatur, Illinois  62526
ImClone Investigational Site Louisville, Kentucky  40202
ImClone Investigational Site Ypsilanti, Michigan  48198
ImClone Investigational Site Minneapolis, Minnesota  55416
ImClone Investigational Site Las Vegas, Nevada  89109
ImClone Investigational Site Portland, Oregon  97239
ImClone Investigational Site Memphis, Tennessee  38104
ImClone Investigational Site Dallas, Texas  75230
ImClone Investigational Site Winston-Salem, North Carolina  27103
ImClone Investigational Site Bismarck, North Dakota  58501
ImClone Investigational Site Philadelphia, Pennsylvania  19107
ImClone Investigational Site Ogden, Utah  84403
ImClone Investigational Site Tucson, Arizona  85712
ImClone Investigational Site Jackson, Mississippi  39202
ImClone Investigational Site Oklahoma City, Oklahoma  73118
ImClone Investigational Site Birmingham, Alabama  35233
ImClone Investigational Site Grand Island, Nebraska  68803