Paclitaxel, Cyclophosphamide, and Doxorubicin Followed by Autologous Dendritic Cells and Surgery With or Without Radiation Therapy and/or Hormone Therapy in Treating Women With Stage II or Stage III Breast Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2011 by University of Nebraska.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
University of Nebraska
ClinicalTrials.gov Identifier:
NCT00499083
First received: July 10, 2007
Last updated: July 6, 2011
Last verified: July 2011
  Purpose

RATIONALE: Drugs used in chemotherapy, such as paclitaxel, cyclophosphamide, and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Injecting the patient's dendritic cells directly into the tumor may stimulate the immune system and stop tumor cells from growing. Radiation therapy uses high-energy x-rays to kill tumor cells. Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking the use of estrogen by the tumor cells. Giving combination chemotherapy together with autologous dendritic cells before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving radiation therapy and hormone therapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying the side effects and how well giving paclitaxel together with cyclophosphamide and doxorubicin followed by autologous dendritic cells and surgery with or without radiation therapy and/or hormone therapy works in treating women with stage II or stage III breast cancer.


Condition Intervention Phase
Breast Cancer
Biological: therapeutic autologous dendritic cells
Drug: aromatase inhibition therapy
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: paclitaxel
Drug: tamoxifen citrate
Genetic: gene expression analysis
Genetic: protein expression analysis
Genetic: reverse transcriptase-polymerase chain reaction
Other: immunoenzyme technique
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Procedure: adjuvant therapy
Procedure: biopsy
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Neoadjuvant Intratumoral Injection of Dendritic Cells in Breast Cancer Translation of Biotechnology Into the Clinic

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • Pathological complete response [ Time Frame: At definitive surgery. ] [ Designated as safety issue: No ]

    Assessed by the institutional pathologist.

    • Grade 1: disappearance of all tumor on microscopic assessment in the breast and LNs
    • Grade 2: presence of in situ carcinoma only in the breast, no invasive tumor, and no tumor found in the LNs
    • Grade 3: presence of invasive carcinoma with stromal alteration, such as sclerosis or fibrosis
    • Grade 4: no or few modifications of the tumor appearance


Secondary Outcome Measures:
  • Inflammatory cell infiltration [ Time Frame: Post-vaccination peripheral blood (PB) after the last chemotherapy. ] [ Designated as safety issue: No ]
    T cell response to tumor-specific Ag, will be measured by ELISPOT assay with a biologic response defined as double the average ELISPOT reactivity in post-vaccination peripheral blood (PB) compared to pre-vaccination PB.

  • Antibody-dependent cell-mediated cytotoxicity [ Time Frame: Post-vaccination peripheral blood (PB) after the last chemotherapy. ] [ Designated as safety issue: Yes ]
    T cell response to tumor-specific Ag, will be measured by ELISPOT assay with a biologic response defined as double the average ELISPOT reactivity in post-vaccination peripheral blood (PB) compared to pre-vaccination PB.

  • Influence of tumor COX-2 and VEGF expression on dendritic cell-mediated tumor-specific immunity [ Time Frame: Post-vaccination peripheral blood (PB) after the last chemotherapy. ] [ Designated as safety issue: No ]
    T cell response to tumor-specific Ag, will be measured by ELISPOT assay with a biologic response defined as double the average ELISPOT reactivity in post-vaccination peripheral blood (PB) compared to pre-vaccination PB.


Estimated Enrollment: 30
Study Start Date: May 2006
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: therapeutic autologous dendritic cells
    injected into the primary breast mass or palpable axillary node, one week after the first, second and third T treatments. If, after a cycle(s) of chemotherapy, no tumor can be localized by ultrasound, the DCs will be injected where the tumor bed was localized by the clip or marker.
    Drug: aromatase inhibition therapy
    Adjuvant hormone therapy for patients having tumors with estrogen and/or progesterone receptors. Premenopausal patients will be treated with tamoxifen. Post or perimenopausal women may receive tamoxifen or an aromatase inhibitor (AI) or those drugs in sequence as determined by the treating oncologist. Hormone therapy will be given for at least 5 years.
    Drug: cyclophosphamide
    600 mg/m2 IV day 1 every 2 weeks for 4 cycles
    Drug: doxorubicin hydrochloride
    60 mg/m2 IV day 1 every 2 weeks for 4 cycles
    Drug: paclitaxel
    175 mg/m2 intravenously (IV) over at least 3 hours day 1 every 2 weeks for 4 cycles.
    Drug: tamoxifen citrate
    Adjuvant hormone therapy for patients having tumors with estrogen and/or progesterone receptors. Premenopausal patients will be treated with tamoxifen. Post or perimenopausal women may receive tamoxifen or an aromatase inhibitor (AI) or those drugs in sequence as determined by the treating oncologist. Hormone therapy will be given for at least 5 years.
    Genetic: gene expression analysis
    IHC for CEA and Survivin with appropriate controls will be done on the tumor biopsy material (preferably from the initial diagnostic biopsy).
    Genetic: protein expression analysis
    Tumor biopsymaterial (preferably from the initial diagnostic biopsy) will be stained by IHC with appropriate controls for COX-2, VEGF A, T cell and Dendritic Cell infiltration.
    Genetic: reverse transcriptase-polymerase chain reaction
    delta Ct (quantitative real time- reverse transcription-polymerase chain reaction (qRT-PCR)) of COX-2 and VEGF will be divided into the upper or lower median and Fisher Exact test used to assess the difference in response.
    Other: immunoenzyme technique

    Estrogen and progesterone receptor, Her2/neu testing: Tumor biopsy material (preferably the initial diagnostic biopsy if tissue is available) will be examined by Immunohistochemistry (IHC) with appropriate controls for estrogen, progesterone receptors and Her2/neu. If the IHC is 2+ or in the indeterminate range, further testing of over-expression of Her2/neu by fluorescent in situ hybridization (FISH) will be done . If this has already been done and reported by the referring hospital, it will not be repeated. These tests are standard of care.

    CEA and Survivin testing: IHC for CEA and Survivin with appropriate controls will be done on the tumor biopsy material (preferably from the initial diagnostic biopsy).

    COX-2 and VEGF A , T cell and Dendritic Cells: Tumor biopsymaterial (preferably from the initial diagnostic biopsy) will be stained by IHC with appropriate controls for COX-2, VEGF A, T cell and Dendritic Cell infiltration.

    Other: immunohistochemistry staining method

    Estrogen and progesterone receptor, Her2/neu testing: Tumor biopsy material (preferably the initial diagnostic biopsy if tissue is available) will be examined by Immunohistochemistry (IHC) with appropriate controls for estrogen, progesterone receptors and Her2/neu. If the IHC is 2+ or in the indeterminate range, further testing of over-expression of Her2/neu by fluorescent in situ hybridization (FISH) will be done . If this has already been done and reported by the referring hospital, it will not be repeated. These tests are standard of care.

    CEA and Survivin testing: IHC for CEA and Survivin with appropriate controls will be done on the tumor biopsy material (preferably from the initial diagnostic biopsy).

    COX-2 and VEGF A , T cell and Dendritic Cells: Tumor biopsymaterial (preferably from the initial diagnostic biopsy) will be stained by IHC with appropriate controls for COX-2, VEGF A, T cell and Dendritic Cell infiltration.

    Other: laboratory biomarker analysis

    Estrogen and progesterone receptor, Her2/neu testing: Tumor biopsy material (preferably the initial diagnostic biopsy if tissue is available) will be examined by Immunohistochemistry (IHC) with appropriate controls for estrogen, progesterone receptors and Her2/neu. If the IHC is 2+ or in the indeterminate range, further testing of over-expression of Her2/neu by fluorescent in situ hybridization (FISH) will be done . If this has already been done and reported by the referring hospital, it will not be repeated. These tests are standard of care.

    CEA and Survivin testing: IHC for CEA and Survivin with appropriate controls will be done on the tumor biopsy material (preferably from the initial diagnostic biopsy).

    COX-2 and VEGF A , T cell and Dendritic Cells: Tumor biopsymaterial (preferably from the initial diagnostic biopsy) will be stained by IHC with appropriate controls for COX-2, VEGF A, T cell and Dendritic Cell infiltration.

    Procedure: adjuvant therapy
    Hormone manipulation Adjuvant hormone therapy for patients having tumors with estrogen and/or progesterone receptors. Premenopausal patients will be treated with tamoxifen. Post or perimenopausal women may receive tamoxifen or an aromatase inhibitor (AI) or those drugs in sequence as determined by the treating oncologist. Hormone therapy will be given for at least 5 years.
    Procedure: biopsy
    Two tumor biopsies will be performed. The first tumor biopsy will be performed before apheresis for diagnostic purposes, and again after completion of the first four chemotherapy treatments. Patients will undergo local anesthesia with lidocaine and 1% epinephrine followed by 1-2 core biopsies of the breast primary and/or palpable axillary node with a 14 gauge, 16 cm. Bard needle or other similar needle. The procedure may be done under ultrasound guidance. If a metal clip or marker has not been previously placed in the tumor, it will be placed before treatment.
    Procedure: conventional surgery
    Definitive breast surgery Surgery will occur two to four weeks after the last course of chemotherapy. Modified radical mastectomy or lumpectomy and standard axillary dissection could be performed and the specific procedure will be decided by the patient and physician team. If a sentinel node dissection was done prior to chemotherapy and was negative, no further node dissection is necessary. A standard node dissection will be necessary if no node assessment was done prior to chemotherapy or if the pre- chemotherapy sentinel node was positive.
    Procedure: neoadjuvant therapy
    Chemotherapy: Paclitaxel (T) 175 mg/m2 intravenously (IV) over at least 3 hours day 1. Repeat every 2 weeks for 4 cycles. IT DCs will be injected into the primary breast mass or palpable axillary node, one week after the first, second and third T treatments.
    Radiation: radiation therapy
    Radiation therapy Radiation is started two to four weeks after surgery for all patients receiving lumpectomy and those patients after mastectomy that the physician feels chest wall radiation is warranted (example: T3 or T4 breast lesion, four or more axillary nodes etc.). The exact doses and methods of administration will be determined by the treating radiation therapist, but should be standard breast radiotherapy and not partial breast or investigational methods.
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed invasive breast cancer meeting the following criteria:

    • Primary tumor ≥ 3 cm by mammography, ultrasound, or palpation AND/OR palpable axillary lymph nodes > 1 cm
    • Survivin- and/or carcinoembryonic antigen-positive by IHC
    • Tumor must be localized by exam or ultrasound to allow tumor injection
    • No stage IV or metastatic disease
  • HER2/neu-negative tumor by IHC

    • If 2+ or in the indeterminate range, further testing of HER2/neu overexpression by fluorescent in situ hybridization (FISH) is required
  • Hormone receptor status known

PATIENT CHARACTERISTICS:

  • Female
  • Pre-, peri-, or postmenopausal
  • ECOG performance status 0-1
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for up to 6 months following completion of study therapy
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Alkaline phosphatase ≤ 1.5 times upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 times ULN
  • AST and ALT ≤ 1.5 times ULN
  • Creatinine < 1.5 times ULN
  • No active serious infections
  • No prior malignancy except adequately treated basal cell or squamous cell skin cancer, noninvasive carcinoma, or other cancer from which the patient has been disease free for 5 years
  • No comorbidity or condition that would interfere with study assessments and procedures or preclude study participation

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy or radiotherapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00499083

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa, Florida, United States, 33612-9497
United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-6805
Sponsors and Collaborators
University of Nebraska
Investigators
Principal Investigator: Elizabeth C. Reed, MD University of Nebraska
Principal Investigator: Kenneth H. Cowan, MD, PhD University of Nebraska
  More Information

Additional Information:
No publications provided

Responsible Party: Elizabeth C. Reed, UNMC Eppley Cancer Center at the University of Nebraska Medical Center
ClinicalTrials.gov Identifier: NCT00499083     History of Changes
Other Study ID Numbers: 072-06, P30CA036727, UNMC-07206
Study First Received: July 10, 2007
Last Updated: July 6, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Nebraska:
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer

Additional relevant MeSH terms:
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Liposomal doxorubicin
Cyclophosphamide
Doxorubicin
Tamoxifen
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014