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

NCT ID: NCT01897441

Last Updated: 2024-12-24

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

31 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-06-30

Study Completion Date

2023-10-25

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Stage IIA Breast Cancer Stage IIB Breast Cancer Stage IIIA Breast Cancer Stage IIIB Breast Cancer Stage IIIC Breast Cancer Stage IV Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Given IV

Cytology Specimen Collection Procedure

Intervention Type OTHER

Correlative studies

Doxorubicin Hydrochloride

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Paclitaxel

Intervention Type DRUG

Given IV

Trastuzumab

Intervention Type BIOLOGICAL

Given IV

Stratum B: HER2-negative

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

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Given IV

Cytology Specimen Collection Procedure

Intervention Type OTHER

Correlative studies

Doxorubicin Hydrochloride

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Paclitaxel

Intervention Type DRUG

Given IV

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.

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Given IV

Cytology Specimen Collection Procedure

Intervention Type OTHER

Correlative studies

Doxorubicin Hydrochloride

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Paclitaxel

Intervention Type DRUG

Given IV

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.

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Given IV

Cytology Specimen Collection Procedure

Intervention Type OTHER

Correlative studies

Doxorubicin Hydrochloride

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Paclitaxel

Intervention Type DRUG

Given IV

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.

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Given IV

Cytology Specimen Collection Procedure

Intervention Type OTHER

Correlative studies

Doxorubicin Hydrochloride

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Paclitaxel

Intervention Type DRUG

Given IV

Trastuzumab

Intervention Type BIOLOGICAL

Given IV

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.

Group Type EXPERIMENTAL

Cytology Specimen Collection Procedure

Intervention Type OTHER

Correlative studies

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Endocrine therapy

Intervention Type DRUG

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.

Interventions

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Cyclophosphamide

Given IV

Intervention Type DRUG

Cytology Specimen Collection Procedure

Correlative studies

Intervention Type OTHER

Doxorubicin Hydrochloride

Given IV

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Paclitaxel

Given IV

Intervention Type DRUG

Trastuzumab

Given IV

Intervention Type BIOLOGICAL

Endocrine therapy

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.

Intervention Type DRUG

Other Intervention Names

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(-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 Cytologic Sampling 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI) ADM Adriacin Adriamycin Adriamycin Hydrochloride Adriamycin PFS Adriamycin RDF ADRIAMYCIN, HYDROCHLORIDE Adriamycine Adriblastina Adriblastine Adrimedac Chloridrato de Doxorrubicina DOX DOXO-CELL Doxolem Doxorubicin.HCl Doxorubin Farmiblastina FI 106 FI-106 hydroxydaunorubicin Rubex Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat ABP 980 Anti-c-ERB-2 Anti-c-erbB2 Monoclonal Antibody Anti-ERB-2 Anti-erbB-2 Anti-erbB2 Monoclonal Antibody Anti-HER2/c-erbB2 Monoclonal Antibody Anti-p185-HER2 c-erb-2 Monoclonal Antibody HER2 Monoclonal Antibody Herceptin Herceptin Biosimilar PF-05280014 Herceptin Trastuzumab Biosimilar PF-05280014 MoAb HER2 Monoclonal Antibody c-erb-2 Monoclonal Antibody HER2 PF-05280014 rhuMAb HER2 Trastuzumab Biosimilar ABP 980 Trastuzumab Biosimilar PF-05280014 Arimidex (anastrozole) Femara (letrozole) Aromasin (exemestane) Nolvadex (tamoxifen) Soltamox (tamoxifen)

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Albert Einstein College of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jesus Anampa, MD

Role: PRINCIPAL_INVESTIGATOR

Albert Einstein College of Medicine

Locations

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Albert Einstein College of Medicine

The Bronx, New York, United States

Site Status

Countries

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United States

References

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Karagiannis GS, Pastoriza JM, Wang Y, Harney AS, Entenberg D, Pignatelli J, Sharma VP, Xue EA, Cheng E, D'Alfonso TM, Jones JG, Anampa J, Rohan TE, Sparano JA, Condeelis JS, Oktay MH. Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mechanism. Sci Transl Med. 2017 Jul 5;9(397):eaan0026. doi: 10.1126/scitranslmed.aan0026.

Reference Type BACKGROUND
PMID: 28679654 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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NCI-2013-01194

Identifier Type: REGISTRY

Identifier Source: secondary_id

P30CA013330

Identifier Type: NIH

Identifier Source: secondary_id

View Link

13-02-079

Identifier Type: -

Identifier Source: org_study_id