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A Phase II Randomized Trial Evaluating the Effect of Trastuzumab on Disease Free Survival in Early Stage HER2-Negative Breast Cancer Patients With ERBB2 Expressing Bone Marrow Disseminated Tumor Cells

Phase 2
18 Years
Not Enrolling
Breast Neoplasms

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Trial Information

A Phase II Randomized Trial Evaluating the Effect of Trastuzumab on Disease Free Survival in Early Stage HER2-Negative Breast Cancer Patients With ERBB2 Expressing Bone Marrow Disseminated Tumor Cells

Inclusion Criteria:

-Histologically confirmed HER2-negative primary invasive ductal or invasive lobular breast
carcinoma. For patients enrolling for neoadjuvant treatment, diagnosis must be clinical
stage II or III; for patients enrolling for adjuvant treatment, diagnosis must be
pathologic stage IIA to IIIC.

Standard HER2 testing will be performed in the surgical specimen at Washington University
according to the standard of care in the Department of Pathology. A HER2-negative primary
breast cancer sample from a patient eligible for randomization should have a HER2 IHC
score of 0 or 1+ Those patients with IHC score of 2+ should be HER2 FISH-negative in
standard testing.

Patient will have undergone staging studies including a CT of the chest/abdomen/pelvis and
bone scan and/or PET scan either prior to the initiation of treatment or prior to entry
into the trial.

- Presence of bone marrow ERBB2 expressing DTCs at the time of diagnosis; bone marrow
aspiration will be performed in consented patients to evaluate DTCs following
pre-registration provided patients meet all eligibility criteria as described in this

- A candidate for adjuvant or neoadjuvant chemotherapy. Adjuvant tamoxifen or aromatase
inhibitors treatment will be allowed for hormone receptor-positive patients.

- At least 18 years old.

- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.

- Adequate cardiac function as demonstrated by LVEF of >55% performed no more than 2
weeks prior to randomization.

- Normal organ and marrow function as defined below:

- leukocytes ≥3,000/mcL

- absolute neutrophil count ≥1,500/mcL

- platelets ≥100,000/mcL

- hemoglobin ≥ 10 g/dL

- total bilirubin ≤within institutional upper limits of normal unless related to
primary disease

- AST(SGOT)/ALT(SGPT) ≤2.0 X institutional upper limit of normal

- Creatinine ≤ 1.5 institutional upper limits of normal OR creatinine clearance
≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional

- Patient (or legally authorized representative) must be able to understand and willing
to sign a written informed consent document.

- If a woman of childbearing potential, patient must use dual forms of effective

Exclusion Criteria:

- Evidence of distant metastasis present by CT scan, bone scan, or physical exam.

- Undergoing treatment with other standard or investigational anti-cancer agents at the
time of enrollment.

- Prior chemotherapy within the 4 weeks prior to pre-registration (6 weeks for

- Prior radiation therapy within the 4 weeks prior to pre-registration.

- Previous treatment with trastuzumab or any other Her2 targeted therapy.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to trastuzumab.

- Presence of an uncontrolled intercurrent illness including, but not limited to,
ongoing or active infection, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
limit compliance with study requirements.

- History of other malignancy ≤ 5 years previous with the exception of basal cell or
squamous cell carcinoma of the skin which were treated with local resection only or
carcinoma in situ of the cervix.

- Pregnant or breastfeeding. Patient must have a negative serum pregnancy test ≤ 7
days from date of registration (if a woman of childbearing potential).

Women of childbearing potential are defined as follows:

- Women with regular menses

- Women with amenorrhea, irregular cycles, or using a contraceptive method that
precludes withdrawal bleeding

- Women who have had a tubal ligation.

Women are considered not to be of childbearing potential for the following reasons:

- The patient has undergone hysterectomy and/or bilateral oophorectomy.

- The patient is post-menopausal defined by amenorrhea for at least 1 year in a woman >
45 years old.

- Clinically important history of active liver disease, including viral or other
hepatitis or cirrhosis.

- Uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, or hypokalemia defined
as less than the lower limit of normal for the institution despite adequate
electrolyte supplementation.

- Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs
resulting in dyspnea at rest.

Inclusion of Women and Minorities

-Breast cancer is rare in men and children. Therefore, this trial is only open to women of
all races and ethnic groups.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Recurrence Rate at 3 years

Outcome Description:

Rate for patients receiving trastuzumab in addition to standard chemotherapy and for patients receiving standard chemotherapy alone; calculated using Cox proportional hazards models

Outcome Time Frame:

3 years after completion of standard chemotherapy and surgery

Safety Issue:


Principal Investigator

Rebecca Aft, M.D., Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Washington University School of Medicine


United States: Institutional Review Board

Study ID:




Start Date:

March 2013

Completion Date:

September 2022

Related Keywords:

  • Breast Neoplasms
  • Breast Neoplasms
  • Neoplasms



Washington University School of Medicine Saint Louis, Missouri  63110