1) Adenovirus p53 Infected DC Vaccine For Breast Cancer, 2) Translation of Biotechnology Into the Clinic
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Number of Participants Who Experienced Toxicity to the Vaccine
研究概览
简要总结
RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving vaccine therapy before and/or after chemotherapy and radiation therapy may cause a stronger immune response.
PURPOSE: This randomized phase I/II trial is studying the side effects of two regimens of vaccine therapy and to see how well they work in treating women who are receiving neoadjuvant or adjuvant chemotherapy and adjuvant radiation therapy for stage III breast cancer that overexpresses p53.
详细描述
OBJECTIVES:
- Determine the safety and toxicity of two different schedules of vaccination comprising p53-infected autologous dendritic cells in women with p53-overexpressing stage III breast cancer undergoing neoadjuvant or adjuvant chemotherapy and adjuvant radiotherapy.
- Determine the immune response, in terms of humoral and cellular response, in patients treated with these regimens.
- Determine antigen-specific immune responses in patients treated with these regimens.
OUTLINE: This is a randomized, open-label study. Patients are randomized to 1 of 2 treatment arms.
All patients undergo apheresis for the collection of peripheral blood monocytes that are cultured with interleukin-4 and sargramostim (GM-CSF) to produce dendritic cells. The dendritic cells are infected with a recombinant adenoviral vector containing the wild-type p53 gene.
Patients receive doxorubicin IV and cyclophosphamide IV every 2 weeks for 8 weeks (4 courses) followed 2 weeks later by paclitaxel IV every 2 weeks for 8 weeks (4 courses). Patients with stage III disease then undergo surgery. Three weeks after completion of paclitaxel (or after surgery for patients with stage III disease), patients undergo radiotherapy once daily for 6.5 weeks. Patients are then receive vaccine therapy as per the arm to which they were randomized.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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:
- •Clinically locally advanced disease (stage III) with a primary tumor at least 4 cm by mammogram, ultrasound, or palpation AND/OR palpable axillary nodes larger than 1 cm
- •Planned neoadjuvant chemotherapy
- •p53-overexpressing tumor by immunohistochemistry
- •Delayed-type hypersensitivity to at least 1 of 3 standard antigens
- •WBC > 4,000/mm^3
- •Platelet count > 100,000/mm^3
- •Bilirubin < 2 times upper limit of normal (ULN)
- •Hepatitis B surface antigen negative
- •Hepatitis C antibody negative
- •Creatinine < 2 times ULNHIV negative
- •Fertile patients must use effective contraception during and for at least 6 months after study participation
排除标准
- •No prior or concurrent autoimmune disorder
- •Not pregnant or nursing/negative pregnancy test
- •No other concurrent illness that would preclude study participation
- •No prior chemotherapy
- •No concurrent participation in another therapeutic clinical trial
结局指标
主要结局
Number of Participants Who Experienced Toxicity to the Vaccine
时间窗: 1 week after each vaccine dose.
This outcome measure looks at the safety of the vaccine by documenting the number of grade 2, 3, or toxicities experienced by participants related to the vaccine.
Peak Immune Response as Measured by Number of Spots Per Cells
时间窗: 6 months after last immunization
This outcome measure examined the importance of vaccine timing on antigen-specific relative to the primary cytotoxic therapy on the augmentation of antigen specific immune responses by measuring the duration of immune responses of participants
Percent of Patients With an Immune Response to p53-infected Autologous Dendritic Cells
时间窗: Through study completion, an average of 18 months
次要结局
未报告次要终点