Phase III Study of Docetaxel + Ramucirumab or Placebo in Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: ramucirumab (IMC-1121B); docetaxel; Placebo
Intervention description: 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.; 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.; 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.
Intervention MeSH terms: Docetaxel; Ramucirumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 1144.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic breast cancer; HER2 negative breast cancer; locally recurrent breast cancer

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.
    

Eligibility criteria:

        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