Chemotherapy Before Surgery and Tissue Sample Collection in Patients With Stage IIA-IIIC Breast Cancer

Albert Einstein College of Medicine

Status: Terminated

Conditions: Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIB Breast Cancer; Stage IIA Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

Treatments: Other: Laboratory Biomarker Analysis; Drug: Doxorubicin Hydrochloride; Drug: Endocrine therapy; Biological: Trastuzumab; Drug: Cyclophosphamide; Drug: Paclitaxel; Other: Cytology Specimen Collection Procedure

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01897441

P30CA013330 (U.S. NIH Grant/Contract)

13-02-079 (Other Identifier)

NCI-2013-01194 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 31 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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31 participants in 6 patient groups

Stratum A: HER2-positive

Experimental group

Description:

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.

Treatment:

Other: Cytology Specimen Collection Procedure

Drug: Paclitaxel

Drug: Cyclophosphamide

Biological: Trastuzumab

Drug: Doxorubicin Hydrochloride

Other: Laboratory Biomarker Analysis

Stratum B: HER2-negative

Experimental group

Description:

Patients receive sequential Paclitaxel followed by Doxorubicin hydrochloride and Cyclophosphamide (AC) as described in Stratum A.

Treatment:

Other: Cytology Specimen Collection Procedure

Drug: Paclitaxel

Drug: Cyclophosphamide

Drug: Doxorubicin Hydrochloride

Other: Laboratory Biomarker Analysis

Stratum C: HER2-negative

Experimental group

Description:

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.

Treatment:

Other: Cytology Specimen Collection Procedure

Drug: Paclitaxel

Drug: Cyclophosphamide

Drug: Doxorubicin Hydrochloride

Other: Laboratory Biomarker Analysis

Stratum I: HER2-negative

Experimental group

Description:

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.

Treatment:

Other: Cytology Specimen Collection Procedure

Drug: Paclitaxel

Drug: Cyclophosphamide

Drug: Doxorubicin Hydrochloride

Other: Laboratory Biomarker Analysis

Stratum II: HER2-positive

Experimental group

Description:

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.

Treatment:

Other: Cytology Specimen Collection Procedure

Drug: Paclitaxel

Drug: Cyclophosphamide

Biological: Trastuzumab

Drug: Doxorubicin Hydrochloride

Other: Laboratory Biomarker Analysis

Stratum III: ER2-positive, HER2-negative

Experimental group

Description:

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.

Treatment:

Other: Cytology Specimen Collection Procedure

Drug: Endocrine therapy

Other: Laboratory Biomarker Analysis