Neoadjuvant Intratumoral Injection of Dendritic Cells in Breast Cancer Translation of Biotechnology Into the Clinic
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 2
- 主要终点
- Number of Patients With Pathological Complete Response
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 120 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
- •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
排除标准
- •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
研究组 & 干预措施
Vaccine
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).
干预措施: doxorubicin hydrochloride (Drug)
Vaccine
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).
干预措施: cyclophosphamide (Drug)
Vaccine
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).
干预措施: therapeutic autologous dendritic cells (Biological)
Vaccine
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).
干预措施: aromatase inhibition therapy (Drug)
Vaccine
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).
干预措施: paclitaxel (Drug)
Vaccine
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).
干预措施: tamoxifen citrate (Drug)
Vaccine
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).
干预措施: gene expression analysis (Genetic)
Vaccine
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).
干预措施: protein expression analysis (Genetic)
Vaccine
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).
干预措施: reverse transcriptase-polymerase chain reaction (Genetic)
Vaccine
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).
干预措施: immunoenzyme technique (Other)
Vaccine
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).
干预措施: immunohistochemistry staining method (Other)
Vaccine
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).
干预措施: laboratory biomarker analysis (Other)
Vaccine
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).
干预措施: adjuvant therapy (Procedure)
Vaccine
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).
干预措施: biopsy (Procedure)
Vaccine
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).
干预措施: conventional surgery (Procedure)
Vaccine
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).
干预措施: neoadjuvant therapy (Procedure)
Vaccine
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).
干预措施: radiation therapy (Radiation)
结局指标
主要结局
Number of Patients With Pathological Complete Response
时间窗: 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
次要结局
- Influence of Tumor COX-2 and VEGF Expression on Dendritic Cell-mediated Tumor-specific Immunity(Post-vaccination peripheral blood (PB) after the last chemotherapy.)
- Antibody-dependent Cell-mediated Cytotoxicity(Post-vaccination peripheral blood (PB) after the last chemotherapy.)
- Inflammatory Cell Infiltration(Post-vaccination peripheral blood (PB) after the last chemotherapy.)