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

NCT01897441 | Terminated Results DMC

• 3 other identifiers: 13-02-079NCI-2013-01194P30CA013330
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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 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

Outcome Measures

Primary Outcomes (1)

• 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 improve normality of the outcome variable.

  Baseline to 6 months

Secondary Outcomes (1)

• Changes in Quantitative Biomarker Levels in Patients With Chemotherapy-responsive and -Resistant Tumors, Including Senescence, Cell Death, TMEM, Mena, and 67LR

  Baseline to 8 weeks (2 courses)

Study Arms (6)

Stratum A: HER2-positive

EXPERIMENTAL

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.

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

Stratum B: HER2-negative

EXPERIMENTAL

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

Drug: Cyclophosphamide; Other: Cytology Specimen Collection Procedure; Drug: Doxorubicin Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel

Stratum C: HER2-negative

EXPERIMENTAL

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.

Drug: Cyclophosphamide; Other: Cytology Specimen Collection Procedure; Drug: Doxorubicin Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel

Stratum I: HER2-negative

EXPERIMENTAL

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.

Drug: Cyclophosphamide; Other: Cytology Specimen Collection Procedure; Drug: Doxorubicin Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel

Stratum II: HER2-positive

EXPERIMENTAL

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.

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

Stratum III: ER2-positive, HER2-negative

EXPERIMENTAL

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.

Other: Cytology Specimen Collection Procedure; Other: Laboratory Biomarker Analysis; Drug: Endocrine therapy

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: (-)-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

Stratum A: HER2-positive; Stratum B: HER2-negative; Stratum C: HER2-negative; Stratum I: HER2-negative; Stratum II: HER2-positive

Cytology Specimen Collection Procedure OTHER

Correlative studies

Also known as: Cytologic Sampling

Stratum A: HER2-positive; Stratum B: HER2-negative; Stratum C: HER2-negative; Stratum I: HER2-negative; Stratum II: HER2-positive; Stratum III: ER2-positive, HER2-negative

Doxorubicin Hydrochloride DRUG

Given IV

Also known as: 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

Stratum A: HER2-positive; Stratum B: HER2-negative; Stratum C: HER2-negative; Stratum I: HER2-negative; Stratum II: HER2-positive

Laboratory Biomarker Analysis OTHER

Correlative studies

Stratum A: HER2-positive; Stratum B: HER2-negative; Stratum C: HER2-negative; Stratum I: HER2-negative; Stratum II: HER2-positive; Stratum III: ER2-positive, HER2-negative

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Stratum A: HER2-positive; Stratum B: HER2-negative; Stratum C: HER2-negative; Stratum I: HER2-negative; Stratum II: HER2-positive

Trastuzumab BIOLOGICAL

Given IV

Also known as: 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

Stratum A: HER2-positive; Stratum II: HER2-positive

Endocrine therapy 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.

Also known as: Arimidex (anastrozole), Femara (letrozole), Aromasin (exemestane), Nolvadex (tamoxifen), Soltamox (tamoxifen)

Stratum III: ER2-positive, HER2-negative

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• Albert Einstein College of Medicine: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Related Publications (1)

• 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.

  PMID: 28679654 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Cyclophosphamide; Doxorubicin; Paclitaxel; Taxes; Trastuzumab; PF-05280014; Anastrozole; Letrozole; exemestane; Tamoxifen

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Stilbenes; Benzylidene Compounds; Benzene Derivatives

Results Point of Contact

• Title: Dr. Jesus Anampa Mesias
• Organization: Albert Einstein College of Medicine

janampa@montefiore.org

718-405-8505

Study Officials

• Jesus Anampa, MD

  Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2013
• First Posted: July 12, 2013
• Study Start: June 1, 2013
• Primary Completion: October 25, 2023
• Study Completion: October 25, 2023
• Last Updated: December 24, 2024
• Results First Posted: December 24, 2024

Record last verified: 2024-11

Locations

US (1)