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

Primary Purpose

Stage IIA Breast Cancer, Stage IIB Breast Cancer, Stage IIIA Breast Cancer

Status

Active

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Cyclophosphamide

Cytology Specimen Collection Procedure

Doxorubicin Hydrochloride

Laboratory Biomarker Analysis

Paclitaxel

Trastuzumab

About this trial

This is an interventional treatment trial for Stage IIA Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Albert Einstein College of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Stratum A (HER2-positive disease)

Stratum B (paclitaxel followed by AC)

Stratum C (AC followed by paclitaxel)

Arm Description

Patients receive paclitaxel IV over 1 hour and trastuzumab IV over 30-90 minutes weekly for 12 weeks. Beginning 2-3 weeks after the last dose of paclitaxel, patients receive doxorubicin hydrochloride IV over 5-10 minutes and cyclophosphamide IV over 30-60 minutes every 2 weeks for 8 weeks

Patients receive paclitaxel, doxorubicin hydrochloride, and cyclophosphamide as in Stratum A.

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.

Outcomes

Primary Outcome Measures

Changes in senescence and secondary biomarkers, including TMEM, mena, and 67LR

Descriptive statistics by treatment group will be presented. The two-sampled t-test will be performed. Appropriate transformation may be used to improved normality of the outcome variable.

Secondary Outcome Measures

Changes in quantitative biomarker levels in patients with chemotherapy-responsive and -resistant tumors, including senescence, cell death, TMEM, mena, and 67LR

Paired T-test or Wilcoxon signed-rank test will be performed. Two-sample t-test will be performed to compare biomarker between the two groups. If the data are not normally distributed, a suitable data transformation such as the log or rank transformation will be applied. Logistic regression models will also be fit to the data with treatment sensitive/resistance category as the outcome and baseline as well as pre-post change in biomarker level as the main predictor variable to obtain estimates of odds ratios unadjusted and adjusted for potential confounders including patients characteristics.

Full Information

NCT ID

NCT01897441

First Posted

July 9, 2013

Last Updated

July 13, 2023

Sponsor

Albert Einstein College of Medicine

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01897441

Brief Title

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

Official Title

Prospective Tissue Collection in Breast Cancer Patients Receiving Preoperative Systemic Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

June 2013 (undefined)

Primary Completion Date

December 2025 (Anticipated)

Study Completion Date

December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Albert Einstein College of Medicine

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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 o 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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

132 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Stratum A (HER2-positive disease)

Arm Type

Experimental

Arm Description

Arm Title

Stratum B (paclitaxel followed by AC)

Arm Type

Experimental

Arm Description

Patients receive paclitaxel, doxorubicin hydrochloride, and cyclophosphamide as in Stratum A.

Arm Title

Stratum C (AC followed by paclitaxel)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

(-)-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

Intervention Description

Given IV

Intervention Type

Other

Intervention Name(s)

Cytology Specimen Collection Procedure

Other Intervention Name(s)

Cytologic Sampling

Intervention Description

Correlative studies

Intervention Type

Drug

Intervention Name(s)

Doxorubicin Hydrochloride

Other Intervention Name(s)

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

Intervention Description

Given IV

Intervention Type

Other

Intervention Name(s)

Laboratory Biomarker Analysis

Intervention Description

Correlative studies

Intervention Type

Drug

Intervention Name(s)

Paclitaxel

Other Intervention Name(s)

Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Intervention Description

Given IV

Intervention Type

Biological

Intervention Name(s)

Trastuzumab

Other Intervention Name(s)

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

Intervention Description

Given IV

Primary Outcome Measure Information:

Title

Changes in senescence and secondary biomarkers, including TMEM, mena, and 67LR

Description

Descriptive statistics by treatment group will be presented. The two-sampled t-test will be performed. Appropriate transformation may be used to improved normality of the outcome variable.

Time Frame

Baseline to 6 months

Secondary Outcome Measure Information:

Title

Changes in quantitative biomarker levels in patients with chemotherapy-responsive and -resistant tumors, including senescence, cell death, TMEM, mena, and 67LR

Description

Time Frame

Baseline to 8 weeks (2 courses)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jesus Anampa, MD

Organizational Affiliation

Albert Einstein College of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Albert Einstein College of Medicine

City

Bronx

State/Province

New York

ZIP/Postal Code

10461

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

28679654

Citation

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. Erratum In: Sci Transl Med. 2017 Jul 19;9(399):

Results Reference

result

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

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