Paclitaxel, Cyclophosphamide & Doxorubicin, Autologous Dendritic Cells & Surgery in Stage II/III Breast Cancer (Women)

NCT00499083 | Completed Phase 2 Results DMC

• 2 other identifiers: 0072-06-FBP30CA036727
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Breast Cancer

Keywords

stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Pathological Complete Response

  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

  At definitive surgery.

Secondary Outcomes (3)

• Inflammatory Cell Infiltration

  Post-vaccination peripheral blood (PB) after the last chemotherapy.

• Antibody-dependent Cell-mediated Cytotoxicity

  Post-vaccination peripheral blood (PB) after the last chemotherapy.

• Influence of Tumor COX-2 and VEGF Expression on Dendritic Cell-mediated Tumor-specific Immunity

  Post-vaccination peripheral blood (PB) after the last chemotherapy.

Study Arms (1)

Vaccine

EXPERIMENTAL

Patients with HER-2/neu negative tumors will receive IT DCs one week after the first three of four cycles of dose dense T therapy and then four cycles of dose dense AC therapy will be given (i.e. T-AC).

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

Interventions

therapeutic autologous dendritic cells BIOLOGICAL

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.

Vaccine

aromatase inhibition therapy DRUG

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.

Also known as: endocrine therapy

Vaccine

cyclophosphamide DRUG

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

Also known as: Cytoxan

Vaccine

doxorubicin hydrochloride DRUG

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

Also known as: Lipodox, Lipodox 50, and Doxil

Vaccine

paclitaxel DRUG

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

Also known as: Abraxane

Vaccine

tamoxifen citrate DRUG

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.

Also known as: Nolvadex

Vaccine

gene expression analysis GENETIC

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

Vaccine

protein expression analysis GENETIC

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.

Vaccine

reverse transcriptase-polymerase chain reaction GENETIC

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.

Vaccine

immunoenzyme technique OTHER

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.

Vaccine

immunohistochemistry staining method OTHER

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.

Vaccine

laboratory biomarker analysis OTHER

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.

Vaccine

adjuvant therapy PROCEDURE

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.

Vaccine

biopsy PROCEDURE

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.

Vaccine

conventional surgery PROCEDURE

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.

Vaccine

neoadjuvant therapy PROCEDURE

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.

Vaccine

radiation therapy RADIATION

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.

Vaccine

Eligibility Criteria

• Age: 19 Years - 120 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Nebraska: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

H. Lee Moffitt Cancer Center and Research Institute, University of South Florida

Tampa, Florida, 33612-9497, United States

Location

Eppley Cancer Center, University of Nebraska Medical Center

Omaha, Nebraska, 68198-6805, United States

Location

Related Publications (1)

• Hong WX, Sagiv-Barfi I, Czerwinski DK, Sallets A, Levy R. Neoadjuvant Intratumoral Immunotherapy with TLR9 Activation and Anti-OX40 Antibody Eradicates Metastatic Cancer. Cancer Res. 2022 Apr 1;82(7):1396-1408. doi: 10.1158/0008-5472.CAN-21-1382.

  PMID: 35135810 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Aromatase Inhibitors; Cyclophosphamide; Doxorubicin; liposomal doxorubicin; Paclitaxel; Albumin-Bound Paclitaxel; Tamoxifen; Gene Expression Profiling; Reverse Transcriptase Polymerase Chain Reaction; Immunoenzyme Techniques; Immunohistochemistry; Chemotherapy, Adjuvant; Biopsy; Neoadjuvant Therapy; Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; 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; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Genetic Techniques; Investigative Techniques; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques; Immunoassay; Immunologic Techniques; Molecular Probe Techniques; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Combined Modality Therapy; Therapeutics; Drug Therapy; Cytodiagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Results Point of Contact

• Title: Elizabeth Reed
• Organization: University of Nebraska Medical Center

ereed@unmc.edu

402-559-5166

Study Officials

• Elizabeth C Reed, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

• Kenneth H Cowan, MD, PhD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2007
• First Posted: July 11, 2007
• Study Start: May 1, 2006
• Primary Completion: July 1, 2009
• Study Completion: January 28, 2010
• Last Updated: September 29, 2023
• Results First Posted: July 2, 2018

Record last verified: 2023-09

Locations

US (2)