Differential Gene Regulation During Neoadjuvant Therapy Trial of Epirubicin/Cyclophosphamide (EC) vs Docetaxel/Capecitabine (DX) Regimens in Patients With Large ER-positive and ER-negative Breast Cancers: A Randomized Phase II Trial.
- Written informed consent
- The diagnosis of breast cancer can be made by fine-needle aspiration (FNA), core, or
tru-cut biopsy. Biopsy must demonstrate invasive adenocarcinoma.
- Patients must have a life expectancy of at least 1 year, excluding their diagnosis of
- Patients must have a mass on clinical or radiological examination of >1 cm and must
be confined to either the breast or to the breast and ipsilateral axilla. Multiple
masses permitted, provided one of them is >1cm.
- Patients may enter prior to ER or Her2 status being known, however if Her2 is
positive, then the patient is withdrawn from the treatment phase of the trial.
- Patients with palpable mass with distant metastasis and/or palpable supraclavicular
lymphadenopathy allowed if definitive local treatment is judged to be necessary.
- Patients may have inflammatory breast cancer.
- At time of entry, patients must have had the following:
- history and physical exam
- blood tests
- chest imaging within the last 3 months (chest x-ray, CT scan, PET/CT)
- bilateral mammogram
- Ultrasound of tumor with placement of clip to localize tumor should it respond
completely to chemotherapy is recommended
- Bone scan and MRI of the breast as clinically indicated.
- Patients with clinically palpable lymph nodes are recommended to have a FNA biopsy to
document the lymph node status. Patients may undergo a sentinel node biopsy procedure
prior to preoperative chemotherapy.
- At time of entry
- White blood cell count (WBC) > 3,000
- platelet count > 100,000
- bilirubin, serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate
oxaloacetate transaminase (SGPT), alkaline phosphatase, and serum creatinine must all
be < 1.2 x upper limit of normal (ULN)
- calculated creatinine clearance [Cockcroft-Gault] > 50 ml/min. normalized to a 1.73
m2 body surface area (BSA). Patients with benign hyperbilirubinemia are also
- Patients with bone pain are eligible for inclusion if bone scan and/or
roentgenological exam fail to disclose metastatic disease, or if metastatic disease
is found, definitive local treatment is to be performed.
- Patients with non-breast malignancies are eligible if they have not received prior
chemotherapy, or extensive radiation therapy, and are free from disease for at least
two years. Patients with squamous or basal carcinoma of the skin that has been
effectively treated, carcinoma in situ of the cervix that has been treated by surgery
only are eligible. Patients with prior or simultaneous lobular or ductal carcinoma
in situ of the ipsilateral or contralateral breast are also eligible. Patients with
bilateral breast cancer for which at least one of the breast cancers meet the
eligibility requirements are also eligible.
- Has a negative serum or urine pregnancy test within 7 days prior to initiation of
chemotherapy (female patients of childbearing potential).
- Patients with Her2 positive breast cancer
- Pregnancy or breast feeding at the time of proposed randomization. Women of
childbearing potential with either a positive or no pregnancy test at baseline. Woman
of childbearing potential not using a reliable and appropriate contraceptive method.
(Postmenopausal woman must have been amenorrheic for at least 12 months to be
considered of non-childbearing potential). Patients will agree to continue
contraception for 30 days from the date of the last study drug administration.
- Participation in any investigational drug study within 4 weeks preceding the start of
- Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity
- Prior therapy for this breast cancer.
- Prior chemotherapy for a different breast cancer. Patients who have received prior
anthracycline therapy for any malignancy are not eligible.
- Nonmalignant systemic disease (cardiovascular, renal, hepatic, etc.) that would
preclude the patient from being subjected to any of the treatment options or surgery
or would prevent prolonged follow-up.
- Active cardiac disease that would preclude the use of epirubicin. This includes:
- Any documented myocardial infarction or unstable angina;
- Any history of documented congestive heart failure;
- Valvular disease with documented cardiac function compromise;
- Patients with cardiomegaly on chest X-ray, or ventricular hypertrophy on EKG, unless
they demonstrate adequate left ventricular ejection fraction (LVEF) > 45% by MUltiple
Gated Acquisition (MUGA) or echocardiogram.
- Patients with a cardiac arrhythmia are eligible, provided the arrhythmia is not
associated with concomitant heart failure or cardiac dysfunction.
- History of uncontrolled seizures, central nervous system disorders or psychiatric
disability judged by the investigator to be clinically significant, precluding
informed consent, or interfering with compliance of oral drug intake.
- Lack of physical integrity of the upper gastrointestinal tract or malabsorption
- Known, existing uncontrolled coagulopathy
- Unwillingness to give written informed consent.
- Unwillingness to participate or inability to comply with the protocol for the
duration of the study.