Chemotherapy Before Surgery and Tissue Sample Collection in Patients With Stage IIA-IIIC Breast Cancer
Purpose
This pilot clinical trial studies chemotherapy before surgery and tissue sample collection in patients with stage IIA-IIIC breast cancer. Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread. Giving doxorubicin hydrochloride, cyclophosphamide, paclitaxel and trastuzumab may kill more tumor cells. Collecting and storing samples of tissue from patients with breast cancer to study in the laboratory may help doctors learn more about how well patients will respond to treatment.
Conditions
- Stage IIA Breast Cancer
- Stage IIB Breast Cancer
- Stage IIIA Breast Cancer
- Stage IIIB Breast Cancer
- Stage IIIC Breast Cancer
- Stage IV Breast Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Criteria
Inclusion Criteria:
- Patients must have histologically confirmed adenocarcinoma of the breast associated
with the following clinical stage: IIA, IIB, IIIA, IIIB, or IIIC; patients with
stage IV disease are also eligible if there is an intention to perform breast
surgery after neoadjuvant therapy is completed, or in patients participating in
clinical trials where surgery after neoadjuvant therapy may be an option (eg. E2108)
- Estrogen receptor (ER), progesterone receptor (PR), and HER2/neu status documented
by core needle biopsy of the primary tumor and/or regional lymph node must be known
prior to beginning systemic therapy
- Patients must have had a bilateral diagnostic mammogram within 6 months of
registration, and may also have a targeted sonography of the breast and/or
ipsilateral axilla and magnetic resonance imaging (MRI) if clinically indicated
- Patients with clinically suspicious axillary lymph node involvement must have either
aspiration cytology or biopsy prior to beginning therapy
- It is strongly encouraged that all patients have metallic clips placed in the tumor
prior to neoadjuvant therapy in order to facilitate evaluation for microscopic
disease at the time of surgery; placement of clips is particularly encouraged for
patients being considered for breast conserving surgery
- No prior chemotherapy, irradiation, or definitive therapeutic surgery (eg,
mastectomy or lumpectomy or axillary dissection) for this malignancy; patients who
have had a prior sentinel lymph node biopsy for this malignancy are eligible
- Patients who received tamoxifen or another selective estrogen receptor modulator
(SERM) for prevention or for other indications (e.g., osteoporosis, prior ductal
carcinoma in situ [DCIS]) are eligible; tamoxifen therapy or other SERMs should be
discontinued at least 1 week before the patient is enrolled on this study
- The patient is medically suitable candidate for preoperative chemotherapy and
surgery in the judgment of the treating physicians
- Ability to understand and the willingness to sign a written informed consent
document, and willing to provide blood samples before and during preoperative
therapy; patients are also asked but not required to have research biopsies
performed before and after therapy
Study Design
- Phase
- N/A
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
Arm | Description | Assigned Intervention |
---|---|---|
Experimental Stratum A: HER2-positive |
Patients receive Paclitaxel 80 mg/m^2 IV infusion over 1 hour for 12 weeks and Trastuzumab 8 mg/kg IV loading dose over 90 minutes, then 6 mg/kg IV every three weeks (after Paclitaxel when given concurrently) for a total of 17 doses over 51 weeks. Beginning 2-3 weeks after the last dose of Paclitaxel, patients receive Doxorubicin hydrochloride 60 mg/m^2 IV over 5-10 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes every 2 weeks for 8 weeks. |
|
Experimental Stratum B: HER2-negative |
Patients receive sequential Paclitaxel followed by Doxorubicin hydrochloride and Cyclophosphamide (AC) as described in Stratum A. |
|
Experimental Stratum C: HER2-negative |
Patients receive sequential Doxorubicin hydrochloride and Cyclophosphamide (AC) followed by Paclitaxel. Patients receive Doxorubicin hydrochloride IV over 5-10 minutes and cyclophosphamide IV over 30-60 minutes every 2 weeks for 8 weeks. Patients then receive paclitaxel IV over 1 hour weekly for 12 weeks. |
|
Experimental Stratum I: HER2-negative |
Patients receive Paclitaxel 80 mg/m^2 IV infusion over 1 hour for 12 weeks followed by Doxorubicin hydrochloride and Cyclophosphamide (AC). Patients receive Doxorubicin hydrochloride 60 mg/m^2 IV over 5-10 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes every 2 weeks for 8 weeks. |
|
Experimental Stratum II: HER2-positive |
Patients receive Paclitaxel 80 mg/m^2 IV infusion over 1 hour for 12 weeks and Trastuzumab 8 mg/kg IV loading dose over 90 minutes, then 6 mg/kg IV every three weeks (after Paclitaxel when given concurrently) for a total of 17 doses over 51 weeks. Beginning 2-3 weeks after the last dose of Paclitaxel, patients receive Doxorubicin hydrochloride 60 mg/m^2 IV over 5-10 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes every 2 weeks for 8 weeks. |
|
Experimental Stratum III: ER2-positive, HER2-negative |
Patients with ER-positive, HER2-negative disease may receive neoadjuvant endocrine therapy (NET) with an aromatase inhibitor: (either Anastrozole 1 mg po daily; Letrozole 2.5 mg po daily, Exemestane 25 mg po daily or Tamoxifen 20 mg po daily) for 4-6 months prior to surgery (or longer if clinically indicated). Anastrozole for 6 months is the preferred regimen for NET. |
|
More Details
- Status
- Terminated
- Sponsor
- Albert Einstein College of Medicine
Study Contact
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the effects of preoperative neoadjuvant paclitaxel and doxorubicin (doxorubicin hydrochloride)/cyclophosphamide (AC) on: senescence; invasion/motility (tumor microenvironment of metastasis [TMEM] and 67 kDa laminin receptor [67LR]). II. To create a biospecimen repository for future studies derived from patients with breast cancer receiving standard neoadjuvant chemotherapy. OUTLINE: Patients with human epidermal growth factor receptor 2 (HER2)-positive disease are assigned to Stratum A, and patients with HER2-negative disease are randomized to Stratum B or C. STRATUM A: Patients receive paclitaxel intravenously (IV) over 1 hour and trastuzumab IV over 30-90 minutes weekly for 12 weeks. Beginning 2-3 weeks later, patients receive doxorubicin hydrochloride IV over 5-10 minutes and cyclophosphamide IV over 30-60 minutes every 2 weeks for 8 weeks STRATUM B: Patients receive paclitaxel, doxorubicin hydrochloride, and cyclophosphamide as in Stratum A. STRATUM C: Patients receive doxorubicin hydrochloride IV over 5-10 minutes and cyclophosphamide IV over 30-60 minutes every 2 weeks for 8 weeks. Patients then receive paclitaxel IV over 1 hour weekly for 12 weeks. Patients undergo surgery 2-6 weeks after the last chemotherapy dose. In all arms, treatment continues in the absence of unacceptable toxicity.