Stage II or Stage III breast cancer
Conditions
Sponsors
Translational Oncology Research International
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Female patient > 18 years 2.Histologically or cytologically proven adenocarcinoma of the breast 3.Stage II (minimum tumor size > 3 cm) or Stage III disease (except inflammatory breast cancer), as defined by the AJCC Staging Manual, 6th Edition, 2002 4.HER2-negative disease (as defined by fluorescence in situ hybridization [FISH]) 5.ECOG performance status 0-1 6.No prior chemotherapy, radiotherapy, or endocrine therapy for invasive or noninvasive breast cancer 7.Normal cardiac function (ejection fraction > lower limit of normal) as determined by MUGA or echocardiogram 8.If female of childbearing potential, pregnancy test is negative and willing to use effective contraception while on treatment and for at least 3 months after the last dose of study therapy 9.Patient is accessible and willing to comply with treatment and follow-up 10.Patient is willing to provide written informed consent prior to the performance of any study-related procedures 11.Required laboratory values a.Absolute neutrophil count > 1.5 x 109/L b.Hemoglobin > 9.0 g/dL c.Platelet count > 100 x 109/L d.Creatinine =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Prior chemotherapy or radiotherapy for Stage II or Stage III breast cancer 2.Inflammatory BC, clinically defined as the presence of erythema or induration involving one-third or more of the breast 3.Prior treatment with an anti-angiogenic agent 4.Prior ipsilateral radiation therapy for invasive or non-invasive breast cancer 5.Bilateral invasive breast cancer 6.Concurrent therapy with any other non-protocol anti-cancer therapy 7.Current therapy with hormone replacement therapy, or any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulators (agents must be stopped prior to randomization) 8.Presence of neuropathy > grade 2 (NCI-CTC version 3.0) at baseline 9.Presence of any non-healing wound, bone fracture, or ulcer, or the presence of clinically significant (> grade 2) peripheral vascular disease 10.History of any other malignancy within the past 5 years, with the exception of non-melanoma skin cancer or carcinoma-in-situ of the cervix 11.Clinically significant cardiovascular disease (e.g., hypertension [BP > 150/100], history of myocardial infarction or stroke within 6 months, unstable angina), New York Heart Association (NYHA) Grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication 12.Active peptic ulcer disease, inflammatory bowel disease, or other gastrointestinal condition increasing the risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning therapy 13.Active, uncontrolled infection requiring parenteral antimicrobials 14.The presence of any other medical or psychiatric disorder that, in the opinion of the treating physician, would contraindicate the use of the drugs in this protocol or place the subject at undue risk for treatment complications 15.Pregnancy or lactation 16.A history of a severe hypersensitivity reaction to bevacizumab, or docetaxel or other drugs formulated with polysorbate 80 17.Evidence of bleeding diathesis or coagulopathy 18.Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to beginning therapy, or anticipation of the need for a major surgical procedure during the course of the study; minor surgical procedure, fine needle aspiration or core biopsy within 7 days prior to beginning therapy 19.Urine protein:creatinine ratio of > 1.0 at screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To evaluate the safety and toxicity of the TAC regimen with the addition of bevacizumab given as preoperative therapy to patients with Stage II or Stage III breast cancer •To estimate change from baseline expression of HIF1a as a measure of tumor angiogenesis, after a single dose of bevacizumab as compared to placebo ;Secondary Objective: •To estimate the rate of CHF in patients receiving TAC with or without bevacizumab •To estimate the rates of left ventricular ejection fraction (LVEF) changes as measured by either a decrease of > 15% from baseline, or > 10% to a value below the lower limit of normal (for the institution), in patients receiving TAC or TAC plus bevacizumab •To investigate the clinical efficacy of TAC and TAC plus bevacizumab by estimating the clinical objective response rate (CR + PR), pathologic complete response rate (pCR), and rate of breast-conserving surgery (BCS) •To estimate the rate of post-surgical wound healing complications in patients who receive surgery after TAC or TAC plus bevacizumab ;Primary end point(s): Efficacy Assessments Clinical •Clinical objective response rate (CR + PR) •Radiographic objective response rate by MRI (CR + PR) •Pathologic complete response rate (pCR) •Percentage of patients able to undergo breast-conserving surgery Molecular •Change in HIF-1a expression | — |
Countries
Ireland
Outcome results
None listed