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A Phase IIb, Randomized, Multicenter, Noncomparative Pilot Study of the Safety & Efficacy of Three Docetaxel-Based Chemotherapy Regimens Plus Bevacizumab ± Trastuzumab for the Adjuvant Treatment of Patients With Node-Positive & High-Risk Node-Negative Breast Cancer

Phase 2
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

A Phase IIb, Randomized, Multicenter, Noncomparative Pilot Study of the Safety & Efficacy of Three Docetaxel-Based Chemotherapy Regimens Plus Bevacizumab ± Trastuzumab for the Adjuvant Treatment of Patients With Node-Positive & High-Risk Node-Negative Breast Cancer

In this study, participants were stratified according to HER2 status at the time of
enrollment. HER2-negative participants were randomized in a 1:1 ratio to either stratum 1
(AC->T sequential + bevacizumab) or stratum 2 (TAC + bevacizumab). All HER2-positive
participants were assigned to stratum 3 (TCH + bevacizumab).

The study included a treatment period of 1 year, followed by a 2 year posttreatment survival
follow-up period.

The following information on clinical trials is provided for information purposes only to
allow participants and physicians to have an initial discussion about the trial. This
information is not intended to be complete information about the trial, to contain all
considerations that may be relevant to potential participation in the trial, or to replace
the advice of a personal physician or health professional.

Inclusion Criteria:

- Women >/= 18 years of age.

- Histologically proven breast cancer with an interval between definitive breast
surgery that includes axillary lymph node (LN) dissection or axillary nodal
evaluation and study registration of < 60 days. (Note: Cycle 1 of chemotherapy
treatment may NOT be infused until > 28 days after the date of definitive breast
surgery and the participant must be recovered from any clinically significant
toxicity thereof.)

- Definitive surgical treatment must be either mastectomy, or breast conserving surgery
with axillary lymph node dissection (axillary lymph node evaluation can be either
full axillary node dissection or sentinel LN evaluation followed by dissection if
sentinel LN is positive) for operable breast cancer (pT1-4 [including inflammatory],
pNO-3, and MO). Margins of resected specimen from definitive surgery must be
histologically free of invasive adenocarcinoma and ductal carcinoma in-situ (DCIS).
Lobular carcinoma in-situ does not count as a positive margin.

- Subjects must be either lymph node-positive (pN1-3) or lymph node-negative (pN0) with
high-risk features as determined by Investigator.

- High-risk, lymph node-negative participants, (pN0) will be defined as subjects having
invasive adenocarcinoma with either a negative sentinel node biopsy (pN0[sn]) OR
negative lymph node dissection (pN0) disease AND tumor size > 2 cm or tumor size >/=
1 cm with at least one of the following factors:

- negative estrogen receptor (ER) and negative progesterone receptor (PR) status

- histologic and/or nuclear Grade 2-3; or

- age < 35 years

- HER2/neu positive or negative tumors are eligible. HER2 positivity must be documented
by fluorescence in situ hybridization (FISH).

- Estrogen and progesterone receptor status must be performed on the primary tumor
prior to study entry. Results must be pending or known at the time of study entry.

- Normal cardiac function must be confirmed by left ventricular ejection fraction
(LVEF) or shortening fraction (multiple-gated acquisition [MUGA] scan or
echocardiography respectively). The result must be greater than the lower limit of
normal (LLN) for the institution.

- Hematology evaluation within 2 weeks prior to study entry:

- Absolute neutrophil count (ANC) >/= 1,500/μL

- Platelets >/= 100,000/μL

- Hemoglobin >/= 9 g/dL

- Hepatic function evaluation within 2 weeks prior to study entry:

- Total bilirubin
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be in
the acceptable range.

- Complete staging work-up as follows: All subjects must have an appropriate
radiographic evaluation, e.g., computed tomography (CT), positron emission tomography
(PET)/CT, and/or (magnetic resonance imaging) MRI of the brain, chest, abdomen and
pelvis, and imaging of bone by either a bone scan or PET scan. In cases of positive
bone imaging, a bone X-ray or MRI evaluation is mandatory to rule out the possibility
of metastatic bone scan disease. Other tests may be performed as clinically
indicated. It is recommended that all baseline staging should be completed within 35
days prior to study entry.

Exclusion Criteria:

- Prior systemic anticancer therapy for breast cancer (immunotherapy, hormonotherapy,

- Prior anthracycline therapy, taxoids or platinum salts for any malignancy.

- Prior radiation therapy for breast cancer or any radiotherapy to the chest wall for
any other malignancy.

- Bilateral invasive breast cancer.

- Pregnant or lactating subjects

- Cardiac disease or risk for same as judged by Investigator

- Other serious illness or medical conditions such as (partial list- review with
Investigator) history of significant neurologic or psychiatric disorders that would
prohibit the understanding and giving of informed consent, active uncontrolled
infection, active peptic ulcer, unstable diabetes mellitus or subjects with
symptomatic, intrinsic lung disease resulting in dyspnea at rest

- Current therapy with any hormonal agent such as raloxifene, tamoxifen, or other
selective estrogen receptor modulators (SERMs), either for osteoporosis or prevention
of breast cancer. Subjects must have discontinued these agents prior to study entry.

- Concurrent treatment with ovarian hormonal replacement therapy. Prior treatment must
be stopped prior to study entry.

- Concurrent treatment with other experimental drugs. Participation in another clinical
trial with any investigational non-marketed drug within 30 days prior to study entry.

- Concurrent treatment with any other anti-cancer therapy.

- Male subjects, as no clinical efficacy or safety data are available from phase I-II

- Chemotherapy and/or bevacizumab may not be given until > 7 days following a minor
surgical procedure. Chemotherapy may be given without bevacizumab in circumstances in
which the participant has recovered sufficiently to receive chemotherapy but has not
yet reached a 28 day time point at which bevacizumab could be administered.

Type of Study:


Study Design:

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

Outcome Measure:

Cardiac Safety - Number of Participants With Grade 3-4 Clinical Congestive Heart Failure (CHF)

Outcome Description:

Participants were evaluated for clinical CHF every 3 weeks during chemotherapy, every 3 months while on maintenance therapy, and every 3 months during the 2-year follow-up period. Left ventricular ejection fraction (LVEF) of CHF was assessed by multi-gated acquisition (MUGA) or echocardiogram (ECHO) performed midway through completion of chemotherapy according to a treatment-specific schedule, every 12 weeks during maintenance therapy, and at 6 and 24 months after completion of maintenance therapy. Grade 3-4 CHF were identified through a clinical review of all study collected investigator verbatim and the Medical Dictionary for Regulatory Activities (MedDRA). The preferred terms (PT) cardiac failure congestive, cardiomyopathy, and ejection fraction decreased were associated with CHF.

Outcome Time Frame:

from the first dose of study medication up to the end of follow-up (up to 3 yrs)

Safety Issue:


Principal Investigator

Vicki Erickson, MSN

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

August 2006

Completion Date:

October 2011

Related Keywords:

  • Breast Cancer
  • Breast Neoplasms



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