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A Phase II Study of Neoadjuvant Chemotherapy With and Without Trastuzumab in Patients With Breast Cancer

Phase 2
19 Years
Open (Enrolling)
Estrogen Receptor-negative Breast Cancer, Estrogen Receptor-positive Breast Cancer, HER2-negative Breast Cancer, HER2-positive Breast Cancer, Progesterone Receptor-negative Breast Cancer, Progesterone Receptor-positive Breast Cancer, Stage IA Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer, Triple-negative Breast Cancer

Thank you

Trial Information

A Phase II Study of Neoadjuvant Chemotherapy With and Without Trastuzumab in Patients With Breast Cancer


I. To evaluate the toxicities and tolerability of a neoadjuvant dose-dense regimen
cyclophosphamide and paclitaxel with or without trastuzumab/radiation therapy (as clinically
indicated) in patients with newly diagnosed stage T1cN0 and II-III breast cancer; followed
by maintenance trastuzumab in human epidermal growth factor receptor 2 (HER2) positive OR
Adriamycin (doxorubicin hydrochloride) followed by radiation therapy (RT) in stage II-III
triple negative HER2 (-), estrogen receptor (ER) (-), progesterone receptor (PR) (-) stage
T1cN0 and II-III breast cancer patients.

II. To determine the pathological complete response rate (pCR) of this treatment regimen.

III. To identify possible gene expression profile signatures from whole genome array
analysis that correlate with clinical response/resistance to chemotherapy as measured by
pathologic complete response rate (pCR).


NEOADJUVANT THERAPY: Patients receive paclitaxel intravenously (IV) over 3 hours and
cyclophosphamide IV over 1 hour on day 1. Patients with HER2-positive cancer also receive
trastuzumab IV over 30 minutes on day 1. Treatment repeats every 14 days for up to 6 courses
in the absence of disease progression or unacceptable toxicity. Patients without metastasis
undergo mastectomy or breast conserving surgery 4-8 weeks later.


HER2-POSITIVE PATIENTS: Patients receive standard radiation therapy. Patients also receive
trastuzumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 13
courses in the absence of disease progression or unacceptable toxicity.

ER/PR POSITIVE PATIENTS: Patients receive standard adjuvant hormonal or endocrine therapy.

STAGE T1cN0 TRIPLE NEGATIVE PATIENTS: Patients receive standard radiation therapy.

STAGE II-III TRIPLE NEGATIVE PATIENTS: Patients receive doxorubicin hydrochloride IV over 15
minutes on day 1. Treatment repeats every 14 days for up to 4 courses in the absence of
disease progression or unacceptable toxicity. Patients also receive standard radiation

After completion of study treatment, patients are followed up every 3 months for 2 years.

Inclusion Criteria:

- Women with histologically proven invasive breast cancer without distant metastases
and lymph node negative and a clinical tumor classification of T1cN0 or stage II-III

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- At least one lesion that can be accurately measured in two dimensions utilizing
mammogram, ultrasound, or magnetic resonance imaging (MRI) images to define specific
size and validate complete clinical and pathologic response

- Patients who received radiation therapy > 5 years ago for malignancies other than
breast cancer and whose radiation therapy field is not overlapping with the 20%
isodose line of current radiation field are eligible, provided that radiation therapy
was completed > 5 years ago and that there is no evidence of the second malignancy at
the time of study entry

- All malignant disease must be able to be encompassed within a single irradiation

- Absolute neutrophil count greater than or equal to 1,500/mcl

- Platelet count equal to or greater than 150,000/mcl

- Hemoglobin > 11gm/dl

- Alkaline phosphatase equal or less than 1.5 times the upper limit of normal (ULN)

- Total bilirubin equal to or less than 1.5 times the ULN

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) no greater than
1.5 times the ULN

- Creatinine less than 1.5 times the ULN

- All included patients must have normal cardiac function as defined by an ejection
fraction of > 50% and no decrease in wall motion by echocardiogram

- The patient must be aware of the neoplastic nature of his/her disease and willingly
provide written, informed consent after being informed of the procedure to be
followed, the experimental nature of the therapy, alternatives, potential benefits,
side-effects, risks, and discomforts

- Women of reproductive potential must be non-pregnant and non-nursing and must agree
to employ an effective barrier method of birth control throughout the study and for
up to 6 months following treatment

- Women of child-bearing potential must have a negative pregnancy test within 7 days of
initiating study; (no childbearing potential is defined as age 55 years or older and
no menses for two years or any age with surgical removal of the uterus and/or both

Exclusion Criteria:

- Any patient with inflammatory breast cancer or stage IV or confirmed metastatic

- Patients who have had any prior chemotherapy, or endocrine therapy for the treatment
of breast cancer or any other cancer

- Patients who cannot undergo surgery

- Patients with a known or documented anaphylactic reaction or allergy to any of
chemotherapy agents used in this protocol, or to antiemetics appropriate for
administration in conjunction with protocol-directed therapy

- Uncontrolled inter-current illness including, but not limited to ongoing or active
infection requiring intravenous antibiotics, symptomatic congestive heart failure,
unstable angina pectoris, or serious, uncontrolled cardiac arrhythmia, that might
jeopardize the ability of the patient to receive the therapy program outlined in this
protocol with reasonable safety

- Patients with preexisting grade II peripheral neuropathy

- Pregnant and nursing women are excluded from this study because the chemotherapy
agents and radiation therapy all have the potential for teratogenic or abortifacient

- Patients with prior malignancy will be excluded except for adequately treated basal
cell or squamous cell skin cancer, adequately treated noninvasive carcinomas

- Inability to cooperate with treatment protocol

- Patients with known human immunodeficiency virus (HIV) infection, infectious
hepatitis, type A, B or C, active hepatitis, or hepatic insufficiency

- Patients may not be receiving or have received any other investigational agents
during/or within 1 month prior

- Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent form

- Myocardial infarction within 6 months prior to enrollment or has New York Heart
Association (NYHA) class III or IV heart failure uncontrolled angina, severe
uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
ischemia or active conduction system abnormalities; prior to study entry, any
electrocardiogram (ECG) abnormality at screening has to be documented by the
investigator as not medically relevant

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

pCR, determined from the surgical specimen and is defined as the absence of invasive carcinoma in both the breast and axilla at microscopic examination of the resection specimen, regardless of the presence of carcinoma in situ

Outcome Description:

The pCR rates and exact one-sided 80% confidence intervals will be calculated. The primary analysis is based on the full analysis set (all treated patients). The pCR rates will be summarized overall and for HER+ and HER- subsets.

Outcome Time Frame:

12 weeks

Safety Issue:


Principal Investigator

Elizabeth Reed

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Nebraska


United States: Institutional Review Board

Study ID:




Start Date:

December 2012

Completion Date:

Related Keywords:

  • Estrogen Receptor-negative Breast Cancer
  • Estrogen Receptor-positive Breast Cancer
  • HER2-negative Breast Cancer
  • HER2-positive Breast Cancer
  • Progesterone Receptor-negative Breast Cancer
  • Progesterone Receptor-positive Breast Cancer
  • Stage IA Breast Cancer
  • Stage II Breast Cancer
  • Stage IIIA Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Triple-negative Breast Cancer
  • Breast Neoplasms



University of Nebraska Medical Center Omaha, Nebraska  68198-3330
Saint Francis Medical Center Grand Island, Nebraska  68802