Clinical Trials /

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

NCT01897441

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

N/A

URL:

https://clinicaltrials.gov/show/NCT01897441

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 13-02-079
  • SECONDARY ID: NCI-2013-01194
  • SECONDARY ID: 13-02-079
  • SECONDARY ID: P30CA013330
  • NCT ID: NCT01897441

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

Interventions

DrugSynonymsArms
Cyclophosphamide(-)-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- 138719Stratum A (HER2-positive disease)
Doxorubicin Hydrochloride5,12-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, RubexStratum A (HER2-positive disease)
PaclitaxelAnzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol KonzentratStratum A (HER2-positive disease)
TrastuzumabABP 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-05280014Stratum A (HER2-positive disease)

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 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.

Trial Arms

NameTypeDescriptionInterventions
Stratum A (HER2-positive disease)ExperimentalPatients 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
  • Cyclophosphamide
  • Doxorubicin Hydrochloride
  • Paclitaxel
  • Trastuzumab
Stratum B (paclitaxel followed by AC)ExperimentalPatients receive paclitaxel, doxorubicin hydrochloride, and cyclophosphamide as in Stratum A.
  • Cyclophosphamide
  • Doxorubicin Hydrochloride
  • Paclitaxel
Stratum C (AC followed by paclitaxel)ExperimentalPatients 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.
  • Cyclophosphamide
  • Doxorubicin Hydrochloride
  • Paclitaxel

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
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Changes in senescence and secondary biomarkers, including TMEM, mena, and 67LR
Time Frame:Baseline to 6 months
Safety Issue:
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.

Secondary Outcome Measures

Measure:Changes in quantitative biomarker levels in patients with chemotherapy-responsive and -resistant tumors, including senescence, cell death, TMEM, mena, and 67LR
Time Frame:Baseline to 8 weeks (2 courses)
Safety Issue:
Description: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.

Details

Phase:N/A
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Albert Einstein College of Medicine

Last Updated

August 13, 2021