Breast CancerPhase 2NCT00499083
Paclitaxel, Cyclophosphamide & Doxorubicin, Autologous Dendritic Cells & Surgery in Stage II/III Breast Cancer (Women)
A Phase 2 study testing therapeutic autologous dendritic cells, aromatase inhibition therapy and cyclophosphamide in people with Breast Cancer, run by University of Nebraska at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 to 120 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- therapeutic autologous dendritic cells, aromatase inhibition therapy and cyclophosphamide
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 May 2006to 28 Jan 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 120 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 18Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Eppley Cancer Center, University of Nebraska Medical Center
Omaha, Nebraska, 68198-6805
H. Lee Moffitt Cancer Center and Research Institute, University of South Florida
Tampa, Florida, 33612-9497
About this study
Official title: Neoadjuvant Intratumoral Injection of Dendritic Cells in Breast Cancer Translation of Biotechnology Into the Clinic
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.
Read the detailed description
OBJECTIVES:
- Assess the safety of intratumoral (IT) autologous dendritic cell (DC) injection in women with stage II or III breast cancer receiving neoadjuvant paclitaxel, cyclophosphamide, and doxorubicin hydrochloride followed by surgery with or without adjuvant radiotherapy and/or hormone therapy.
- Determine the clinical and pathologic response in patients treated with this regimen.
- Determine the immune response, in terms of tumor cell apoptosis and the presence and characterization of tumor infiltrating white blood cells in resected breast cancer, in patients treated with this regimen.
- Determine if IT DC injections administered during neoadjuvant chemotherapy-induced tumor cell apoptosis can induce T-cell responses to tumor antigens in these patients.
OUTLINE: This is an open-label study.
- Leukapheresis: Patients undergo leukapheresis at baseline to collect peripheral blood mononuclear cells for dendritic cell (DC) culture.
- Neoadjuvant, dose-dense chemotherapy: Patients receive paclitaxel IV over at least 3 hours on day 1 and filgrastim (G-CSF) subcutaneously (SC) on days 4-14 or pegfilgrastim SC on day 2. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Beginning 2 weeks after completion of paclitaxel chemotherapy, patients receive cyclophosphamide IV and doxorubicin hydrochloride IV on day 1 and G-CSF SC on days 4-14 or pegfilgrastim SC on day 2. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
- Intratumoral injection of autologous DCs: Intratumoral autologous DCs are injected into the primary breast mass or palpable axillary node on day 7 of the 1st, 2nd, and 3rd courses of paclitaxel chemotherapy. If no tumor can be localized by ultrasound after a course of chemotherapy, the DCs are then injected into the site of the tumor bed previously localized by clip or marker. In the event that the previously injected primary tumor cannot be localized by ultrasound, a palpable lymph node, if still present, should be injected rather than the tissue next to the primary tumor clip or marker.
- Definitive breast surgery: Within 2-4 weeks after completion of neoadjuvant chemotherapy, patients undergo modified radical mastectomy or lumpectomy with or without standard axillary node dissection.* NOTE: *Standard axillary node dissection is only required if no node assessment was done prior to chemotherapy or if the pre-chemotherapy sentinel node was positive.
- Radiotherapy: Patients undergoing lumpectomy or those with residual disease requiring chest wall radiotherapy after mastectomy (e.g., T3 or T4 breast lesions or 4 or more axillary lymph nodes) undergo radiotherapy 2-4 weeks after surgery.
- Hormone therapy: Patients with estrogen and/or progesterone receptor-positive tumors receive adjuvant hormone therapy for ≥ 5 years. Premenopausal patients receive tamoxifen citrate and post- or perimenopausal patients receive either tamoxifen citrate or an aromatase inhibitor (AI), or both of these drugs in sequence, as determined by the treating oncologist.
Peripheral blood samples are obtained during each DC injection, at staging/biopsy, and then periodically for up to 2 years. Blood samples are analyzed by ELISPOT and ELISA assays for evaluation of immune response.
Tumor tissue is obtained by core biopsy of the breast primary and/or palpable axillary lymph node at baseline and again after completion of paclitaxel chemotherapy. Tumor tissue is analyzed by IHC and RT-PCR for COX-2 and VEGF-A and -C expression levels, as well as T-cell and DC infiltration of the tumor. T-cell and DC infiltration is evaluated for correlation with clinical outcomes at diagnosis, at the midpoint biopsy following paclitaxel chemotherapy, and at definitive surgery.
After completion of study therapy, patients are followed periodically for up to 2 years.
- Conditions
- Breast Cancer
- Being tested
- therapeutic autologous dendritic cells, aromatase inhibition therapy, cyclophosphamide, doxorubicin hydrochloride, paclitaxel
- Keywords
- stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
therapeutic autologous dendritic cellsBiological
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.
aromatase inhibition therapyDrug
Also called endocrine 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.
cyclophosphamideDrug
Also called Cytoxan
600 mg/m2 IV day 1 every 2 weeks for 4 cycles
Also called Lipodox, Lipodox 50, and Doxil
60 mg/m2 IV day 1 every 2 weeks for 4 cycles
paclitaxelDrug
Also called Abraxane
175 mg/m2 intravenously (IV) over at least 3 hours day 1 every 2 weeks for 4 cycles.
tamoxifen citrateDrug
Also called Nolvadex
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.
gene expression analysisGenetic
IHC for CEA and Survivin with appropriate controls will be done on the tumor biopsy material (preferably from the initial diagnostic biopsy).
protein expression analysisGenetic
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.
reverse transcriptase-polymerase chain reactionGenetic
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.
immunoenzyme techniqueOther
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.
immunohistochemistry staining methodOther
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.
laboratory biomarker analysisOther
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.
adjuvant therapyProcedure or surgery
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.
biopsyProcedure or surgery
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.
conventional surgeryProcedure or 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.
neoadjuvant therapyProcedure or surgery
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 therapyRadiation
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: At definitive surgery.
Secondary outcomes (3)
Inflammatory Cell Infiltration
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.
Measured: Post-vaccination peripheral blood (PB) after the last chemotherapy.
Antibody-dependent Cell-mediated Cytotoxicity
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.
Measured: Post-vaccination peripheral blood (PB) after the last chemotherapy.
Influence of Tumor COX-2 and VEGF Expression on Dendritic Cell-mediated Tumor-specific Immunity
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.
Measured: Post-vaccination peripheral blood (PB) after the last chemotherapy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2007 (estimated)
- Study start1 May 2006
- Primary completion1 Jul 2009
- Study completion28 Jan 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Elizabeth C Reed, MD, Principal investigator, University of NebraskaKenneth H Cowan, MD, PhD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00499083
- Sponsor's protocol ID
- 0072-06-FB
- Other IDs
- P30CA036727
- Status last verified
- Sep 2023
- First submitted
- 10 Jul 2007
- Last updated
- 29 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 35135810
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Intratumoral Injection of Dendritic Cells in Breast Cancer Translation of Biotechnology Into the Clinic
- ClinicalTrials.gov ID
- NCT00499083
- Acronym / sponsor ID
- 0072-06-FB
- Conditions
- Breast Cancer
- Keywords
- stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 1 May 2006 (actual)
- Primary completion
- 1 Jul 2009 (actual)
- Study completion
- 28 Jan 2010 (actual)
- First posted
- 11 Jul 2007 (estimated)
- Results
- Posted 2 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVES:
- Assess the safety of intratumoral (IT) autologous dendritic cell (DC) injection in women with stage II or III breast cancer receiving neoadjuvant paclitaxel, cyclophosphamide, and doxorubicin hydrochloride followed by surgery with or without adjuvant radiotherapy and/or hormone therapy.
- Determine the clinical and pathologic response in patients treated with this regimen.
- Determine the immune response, in terms of tumor cell apoptosis and the presence and characterization of tumor infiltrating white blood cells in resected breast cancer, in patients treated with this regimen.
- Determine if IT DC injections administered during neoadjuvant chemotherapy-induced tumor cell apoptosis can induce T-cell responses to tumor antigens in these patients.
OUTLINE: This is an open-label study.
- Leukapheresis: Patients undergo leukapheresis at baseline to collect peripheral blood mononuclear cells for dendritic cell (DC) culture.
- Neoadjuvant, dose-dense chemotherapy: Patients receive paclitaxel IV over at least 3 hours on day 1 and filgrastim (G-CSF) subcutaneously (SC) on days 4-14 or pegfilgrastim SC on day 2. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Beginning 2 weeks after completion of paclitaxel chemotherapy, patients receive cyclophosphamide IV and doxorubicin hydrochloride IV on day 1 and G-CSF SC on days 4-14 or pegfilgrastim SC on day 2. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
- Intratumoral injection of autologous DCs: Intratumoral autologous DCs are injected into the primary breast mass or palpable axillary node on day 7 of the 1st, 2nd, and 3rd courses of paclitaxel chemotherapy. If no tumor can be localized by ultrasound after a course of chemotherapy, the DCs are then injected into the site of the tumor bed previously localized by clip or marker. In the event that the previously injected primary tumor cannot be localized by ultrasound, a palpable lymph node, if still present, should be injected rather than the tissue next to the primary tumor clip or marker.
- Definitive breast surgery: Within 2-4 weeks after completion of neoadjuvant chemotherapy, patients undergo modified radical mastectomy or lumpectomy with or without standard axillary node dissection.* NOTE: *Standard axillary node dissection is only required if no node assessment was done prior to chemotherapy or if the pre-chemotherapy sentinel node was positive.
- Radiotherapy: Patients undergoing lumpectomy or those with residual disease requiring chest wall radiotherapy after mastectomy (e.g., T3 or T4 breast lesions or 4 or more axillary lymph nodes) undergo radiotherapy 2-4 weeks after surgery.
- Hormone therapy: Patients with estrogen and/or progesterone receptor-positive tumors receive adjuvant hormone therapy for ≥ 5 years. Premenopausal patients receive tamoxifen citrate and post- or perimenopausal patients receive either tamoxifen citrate or an aromatase inhibitor (AI), or both of these drugs in sequence, as determined by the treating oncologist.
Peripheral blood samples are obtained during each DC injection, at staging/biopsy, and then periodically for up to 2 years. Blood samples are analyzed by ELISPOT and ELISA assays for evaluation of immune response.
Tumor tissue is obtained by core biopsy of the breast primary and/or palpable axillary lymph node at baseline and again after completion of paclitaxel chemotherapy. Tumor tissue is analyzed by IHC and RT-PCR for COX-2 and VEGF-A and -C expression levels, as well as T-cell and DC infiltration of the tumor. T-cell and DC infiltration is evaluated for correlation with clinical outcomes at diagnosis, at the midpoint biopsy following paclitaxel chemotherapy, and at definitive surgery.
After completion of study therapy, patients are followed periodically for up to 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vaccine | Experimental | 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 therapyPatients 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). |
Who may qualify
- Ages
- 19 to 120 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Histologically confirmed invasive breast cancer meeting the following criteria:
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| therapeutic autologous dendritic cellsinjected 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. | Biological | Vaccine |
| aromatase inhibition therapyAlso: endocrine therapyAdjuvant 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 | Vaccine |
| cyclophosphamideAlso: Cytoxan600 mg/m2 IV day 1 every 2 weeks for 4 cycles | Drug | Vaccine |
| doxorubicin hydrochlorideAlso: Lipodox, Lipodox 50, and Doxil60 mg/m2 IV day 1 every 2 weeks for 4 cycles | Drug | Vaccine |
| paclitaxelAlso: Abraxane175 mg/m2 intravenously (IV) over at least 3 hours day 1 every 2 weeks for 4 cycles. | Drug | Vaccine |
| tamoxifen citrateAlso: NolvadexAdjuvant 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 | Vaccine |
| gene expression analysisIHC for CEA and Survivin with appropriate controls will be done on the tumor biopsy material (preferably from the initial diagnostic biopsy). | Genetic | Vaccine |
| protein expression analysisTumor 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 | Vaccine |
| reverse transcriptase-polymerase chain reactiondelta 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. | Genetic | Vaccine |
| immunoenzyme techniqueEstrogen 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 | Vaccine |
| immunohistochemistry staining methodEstrogen 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 | Vaccine |
| laboratory biomarker analysisEstrogen 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 | Vaccine |
| adjuvant therapyHormone 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 or surgery | Vaccine |
| biopsyTwo 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 or surgery | Vaccine |
| conventional surgeryDefinitive 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 or surgery | Vaccine |
| neoadjuvant therapyChemotherapy: 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. | Procedure or surgery | Vaccine |
| radiation therapyRadiation 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. | Radiation | Vaccine |
Primary outcome
Number of Patients With Pathological Complete Response
Time frame: At definitive surgery.
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
3 secondary outcomes
Inflammatory Cell Infiltration
Time frame: Post-vaccination peripheral blood (PB) after the last chemotherapy.
Antibody-dependent Cell-mediated Cytotoxicity
Time frame: Post-vaccination peripheral blood (PB) after the last chemotherapy.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35135810Hong 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elizabeth C Reed, MD principal investigator
University of Nebraska
Kenneth H Cowan, MD, PhD principal investigator
University of Nebraska
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing therapeutic autologous dendritic cells, aromatase inhibition therapy and cyclophosphamide in people with Breast Cancer, run by University of Nebraska at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients With Pathological Complete Response (time frame: At definitive surgery.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00499083, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2023.