Optic

ID

Name

0072-06-FB

Description

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.

Trial arms

Trial start

2006-05-01

Estimated PCD

2009-07-01

Trial end

2010-01-28

Status

Completed

Phase

Early phase I

Treatment

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.

Arms:

Vaccine

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.

Arms:

Vaccine

Other names:

endocrine therapy

cyclophosphamide

600 mg/m2 IV day 1 every 2 weeks for 4 cycles

Arms:

Vaccine

Other names:

Cytoxan

doxorubicin hydrochloride

60 mg/m2 IV day 1 every 2 weeks for 4 cycles

Arms:

Vaccine

Other names:

Lipodox, Lipodox 50, and Doxil

paclitaxel

175 mg/m2 intravenously (IV) over at least 3 hours day 1 every 2 weeks for 4 cycles.

Arms:

Vaccine

Other names:

Abraxane

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.

Arms:

Vaccine

Other names:

Nolvadex

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).

Arms:

Vaccine

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.

Arms:

Vaccine

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.

Arms:

Vaccine

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.

Arms:

Vaccine

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.

Arms:

Vaccine

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.

Arms:

Vaccine

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.

Arms:

Vaccine

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.

Arms:

Vaccine

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.

Arms:

Vaccine

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.

Arms:

Vaccine

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.

Arms:

Vaccine

Size

17

Primary endpoint

Number of Patients With Pathological Complete Response

At definitive surgery.

Eligibility criteria

Inclusion Criteria: * 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 o 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 * Female * Pre-, peri-, or postmenopausal * ECOG performance status 0-1 * 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 Exclusion Criteria: * No prior chemotherapy or radiotherapy * 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 * Not pregnant or nursing/negative pregnancy test

Protocol

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Updated at

2023-09-29

Organization

University of Nebraska

Product

Therapeutic Autologous Dendritic Cells

Indication

Breast Cancer

Product

Aromatase Inhibition Therapy

Drug

cyclophosphamide