Docetaxel, Carboplatin, Trastuzumab and Bevacizumab (TCH+B) For Early-Stage HER-2/Neu(+) Breast Cancer and Bone Marrow Micrometastases
- Patient with biopsy-proven primary stage I-III infiltrating adenocarcinoma of the
- HER-2/neu (+) as determined by either IHC (3+) or FISH (≥ 2.2-fold amplification).
- Age ≥ 18 years.
- ECOG performance status 0-1.
- Negative CT C/A/P and TBBS.
- LVEF > 50% by MUGA or echocardiogram performed within 28 days prior to enrollment
- Positive BM aspirate for BC micrometastases by CLIA-certified laboratory.
- Adequate hematologic, hepatic, and renal function. All tests must be obtained ≤ 4
weeks prior to randomization.
- Hematologic: Absolute neutrophil count > 1,500/mm3 Hemoglobin > 10.0 g/dl
Platelet count > 100,000/mm3.
- Hepatic: Total bilirubin must be within normal limits. Transaminases (AST and/or
ALT) may be < 2.5 x institutional upper limit of normal (ULN) if alkaline
phosphatase is < ULN, or alkaline phosphatase may be < 4 x ULN if transaminases
are < ULN
- Renal: Normal creatinine and BUN; if abnormal, calculated creatinine clearance
must be> 60 mg/dL
- Patients must be disease-free of prior invasive malignancies for ≥ 5 years, with the
exception of curatively-treated basal cell or squamous cell carcinoma of the skin or
carcinoma in situ of the cervix.
- Surgery: all patients must have completed surgery with sentinel and/or axillary
lymph node dissection according to participating institutional guidelines.
- Women of childbearing potential must have a negative pregnancy test and must be
willing to consent to using an accepted and effective barrier form method of
contraception while on treatment and for a reasonable period thereafter.
- Patients must provide written informed consent.
- Note: Hormonal therapy: patients with ER+ and/or PR+ tumors may receive concurrent
hormonal therapy according to participating institutional guidelines. The choice of
hormonal therapy is at the discretion of the treating physician.
- Note: Radiation therapy: patients receiving adjuvant radiation therapy to the
involved breast (after partial mastectomy) or chest wall (after mastectomy) may
receive concurrent trastuzumab and bevacizumab therapy.
- Known metastatic BC.
- Concomitant malignancies or previous malignancies within the last 5 years, with the
exception of adequately treated basal or squamous cell carcinoma of the skin or
carcinoma in situ of the cervix.
- Pregnant or lactating women.
- Prior chemotherapy, hormonal therapy, trastuzumab and bevacizumab therapy.
- History of significant cardiac disease, cardiac risk factors or uncontrolled
- Ejection fraction <50% or below the lower limit of the institutional normal range,
whichever is lower.
- Hypersensitivity to trial medications.
- Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs,
resulting in dyspnea at rest.
- Active or uncontrolled infection.
- Psychiatric, addictive, or any disorder that compromises the ability to give informed
consent to participate in or to comply with the requirements of the study.
- Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or
diastolic blood pressure > 100 mmHg on antihypertensive medications)
- Any prior history of hypertensive crisis or hypertensive encephalopathy
- New York Heart Association (NYHA) Grade II or greater congestive heart failure
- History of stroke or transient ischemic attack within 6 months prior to study
- Known CNS disease
- Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
- Symptomatic peripheral vascular disease
- Evidence of bleeding diathesis or coagulopathy
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to study enrollment or anticipation of need for major surgical procedure during
the course of the study
- Core biopsy or other minor surgical procedure, excluding placement of a vascular
access device, within 7 days prior to study enrollment
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to study enrollment
- Serious, non-healing wound, ulcer, or bone fracture
- Proteinuria at screening as demonstrated by either
- Urine protein:creatinine (UPC) ratio >/= 1.0 at screening OR
- Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on
dipstick urinalysis at baseline should undergo a 24 hour urine collection and must
demonstrate ≤ 1g of protein in 24 hours to be eligible).
- Known hypersensitivity to any component of bevacizumab
- Pregnant (positive pregnancy test) or lactating. Use of effective means of
contraception (men and women) in subjects of child-bearing potential
- History of stroke or transient ischemic attack at any time
- History of myocardial infarction or unstable angina within 12 months of study