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

• Status: Completed
• Trial end date: 2020-11-19
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Eli Lilly and Company
• Treatments: Docetaxel; Ramucirumab

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