A Phase I Vaccine Safety and Chemotherapy Dose-Finding Trial of an Allogeneic GM-CSF-Secreting Breast Cancer Vaccine Given in a Specifically Timed Sequence With Immunomodulatory Doses of Cyclophosphamide and Doxorubicin
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Immune resp. of HER-2/neu by serum antibody titers, delayed hypersensitivity to HER-2/neu-derived peptides, and CD4+ T-cell resp. by ELISPOT at days 28-42 after each vaccination and days 56-84 after third vaccination
研究概览
简要总结
RATIONALE: Vaccines made from a person's tumor cells may make the body build an immune response to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide and doxorubicin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining vaccine therapy with cyclophosphamide and doxorubicin may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of cyclophosphamide and doxorubicin when given with vaccine therapy in treating women with stage IV breast cancer.
详细描述
OBJECTIVES:
Primary
- Determine the safety of vaccination comprising allogeneic sargramostim (GM-CSF)-secreting breast cancer cells with or without immunomodulation using cyclophosphamide and doxorubicin in women with stage IV breast cancer.
- Determine the doses of cyclophosphamide and doxorubicin that maximize vaccine-induced immunity, in terms of immune response to HER2/neu, in patients treated with these regimens.
- Compare in vivo immune response induced by these regimens, as measured by immunohistochemical analysis of vaccine site biopsies from these patients, with responses seen in prior preclinical and clinical studies.
Secondary
- Determine the time to disease progression in patients treated with these regimens.
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
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed adenocarcinoma of the breast
- •Stage IV disease
- •Stable disease for ≥ 28 days
- •Measurable or evaluable disease OR no evidence of disease
- •Not eligible for potentially curative therapy
- •Adequately treated CNS metastases are allowed
- •Hormone receptor status:
- •Not specified
- •HER-2/neu status:
- •Not specified
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Menopausal status
- •Not specified
- •Performance status
- •Life expectancy
- •Not specified
- •Hematopoietic
- •Absolute neutrophil count > 1,000/mm^3
- •Platelet count > 100,000/mm^3
- •Bilirubin ≤ 2.0 mg/dL (unless due to Gilbert's syndrome)
- •AST and ALT ≤ 2 times upper limit of normal (ULN)
- •Alkaline phosphatase ≤ 5 times ULN
- •Creatinine < 2.0 mg/dL
- •Cardiovascular
- •Ejection fraction ≥ 45% by echocardiogram or MUGA
- •Asthma or chronic obstructive pulmonary disease allowed provided daily systemic corticosteroid therapy is not required
- •Immunologic
- •No active autoimmune disease requiring systemic immunosuppressive therapy, including any of the following:
- •Inflammatory bowel disease
- •Systemic vasculitis
- •Scleroderma
- •Psoriasis
- •Multiple sclerosis
- •Hemolytic anemia
- •Immune-mediated thrombocytopenia
- •Rheumatoid arthritis
- •Systemic lupus erythematosus
- •Sjögren's syndrome
- •Sarcoidosis
- •Other rheumatologic disease
- •HIV negative
- •No active acute or chronic infection
- •No allergy to corn
- •No other malignancy within the past 5 years except carcinoma in situ of the cervix, superficial nonmelanoma skin cancer, or superficial bladder cancer
- •No active major medical or psychosocial problem that would preclude study participation
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 3 months after study participation
- 另有 21 项未显示
排除标准
- 未提供
结局指标
主要结局
Immune resp. of HER-2/neu by serum antibody titers, delayed hypersensitivity to HER-2/neu-derived peptides, and CD4+ T-cell resp. by ELISPOT at days 28-42 after each vaccination and days 56-84 after third vaccination
时间窗: 4 years
Toxicity of vaccine w/ & w/o cyclophosphamide+doxorubicin by history and phys. exam. at 28-42 days after each vaccination, 56-84 days after third vaccination, 6 months after first vaccination, and annually after first vaccination
时间窗: 4 years
Toxicity of vaccine w/ & w/o cyclophosphamide+doxorubicin by CBC w/ differential at days 7, 14, 21, and 28-42 days after each vaccination, 56-84 days after third vaccination, 6 months after first vaccination, and annually after first vaccination
时间窗: 4 years
Toxicity of vaccine w/ & w/o cyclophosphamide+doxorubicin by comprehensive metabolic panel at day 7 and 28-42 days after each vaccination, 56-84 days after third vaccination, 6 months after first vaccination, and annually after first vaccination
时间窗: 4 years
Immune responses by immunohistochemical analysis of vaccine site biopsies at days 3 and 7 after the first and third vaccinations
时间窗: 4 years
次要结局
- Time to disease progression by history and physical examination, computed tomography, bone scans, and tumor markers as appropriate at days 28-42 after third and fourth vaccinations and days 56-84 after third vaccination(4 years)