A Phase I Study of a DNA Plasmid Based Vaccine Encoding the HER-2/Neu Intracellular Domain in Subjects With HER-2/Neu (HER2) Overexpressing Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Safety as measured by NCI CTCAE v 3.0
研究概览
简要总结
RATIONALE: Vaccines may help the body build an effective immune response to kill tumor cells. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Giving vaccine therapy together with sargramostim may be an effective treatment for breast cancer and ovarian cancer. PURPOSE: This phase I trial is studying the side effects and identifying the best dose of vaccine therapy when given together with sargramostim in treating patients with stage III-IV breast cancer or ovarian cancer.
详细描述
PRIMARY OBJECTIVES: I. To determine the safety of intradermal administration of 3 doses of a plasmid-based DNA vaccine encoding the ICD of HER2 administered with a fixed dose of GM-CSF. II. To determine whether a plasmid DNA vaccine encoding the ICD of HER2 can elicit HER2 specific immune responses. SECONDARY OBJECTIVES: I. To determine if the dose of the plasmid-based DNA vaccine effects immunologic responses. II. To determine the persistence of DNA at the site of vaccination. OUTLINE: This is a dose-escalation study of a plasmid-based DNA (pNGVL3-hICD) vaccine. Patients receive pNGVL3-hICD vaccine admixed with GM-CSF intradermally once a month for 3 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically for up to 15 years with primary physicians.
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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Breast cancer: stage III or stage IV breast cancer with metastasis in remission and defined as NED (no evidence of disease); stable or healing bone disease by radiologic evaluation which may include, but is not limited to, bone scan, MRI, or PET scan documented within 90 days of enrollment to study and NED status for extraskeletal metastasis
- •Ovarian cancer: stage III or stage IV ovarian cancer in first complete remission with a normal AND stable CA-125; thus, two sequential normal CA-125 values will need to be documented; a minimum of 30 days between 2 sequential CA-125 values; the most recent will be within 2 weeks of enrollment into study
- •HER2 overexpression by immunohistochemistry (IHC) of 2+ or 3+ in their primary tumor or metastasis, and if overexpression is 2+ by IHC or in the absence of IHC, then patients must have documentation of HER2 gene amplification by FISH
- •Eligible subjects must have completed appropriate treatment for their primary disease and be off cytotoxic chemotherapy and corticosteroids for at least 1 month prior to enrollment; patients with stage III/IV breast cancer who have completed chemotherapy and are continued on trastuzumab monotherapy are eligible; hormonal and bisphosphanate therapies are allowed
- •Subjects must have a Performance Status Score (Zubrod/ECOG Scale) = 0
- •All subjects must no longer be able to bear children
- •Hematocrit >= 30
- •Platelet count >= 100,000
- •WBC >= 3,000/ul
- •Creatinine =< 2.0 or creatinine clearance >= 60 ml/minute
- •Serum bilirubin < 1.5 mg/dl
- •SGOT < 2 x ULN
- •Subjects must have recovered from major infections and/or surgical procedures and, in the opinion of the investigator, not have a significant active concurrent medical illness precluding protocol treatment or survival
- •Normal ANA, anti-dsDNA and C3
- •Patients on trastuzumab monotherapy must have adequate cardiac function as demonstrated by normal ejection fraction (EF) of MUGA scan or echocardiogram
排除标准
- •Subjects cannot be simultaneously enrolled on other treatment studies
- •Any contraindication to receiving GM-CSF based vaccine products
- •Prior known history of cardiac disease, specifically restrictive cardiomyopathy, unstable angina within the last 6 months prior to enrollment, New York Heart Association functional class III-IV heart or symptomatic pericardial effusion
- •Prior known history of pulmonary disease other than controlled asthma
- •Active autoimmune disease
- •Subjects cannot have active immunodeficiency disorder, e.g., HIV
研究组 & 干预措施
Arm I
Patients receive pNGVL3-hICD vaccine admixed with GM-CSF intradermally once a month for 3 months in the absence of disease progression or unacceptable toxicity.
干预措施: pNGVL3-hICD vaccine (Biological)
Arm I
Patients receive pNGVL3-hICD vaccine admixed with GM-CSF intradermally once a month for 3 months in the absence of disease progression or unacceptable toxicity.
干预措施: sargramostim (Biological)
Arm I
Patients receive pNGVL3-hICD vaccine admixed with GM-CSF intradermally once a month for 3 months in the absence of disease progression or unacceptable toxicity.
干预措施: flow cytometry (Other)
Arm I
Patients receive pNGVL3-hICD vaccine admixed with GM-CSF intradermally once a month for 3 months in the absence of disease progression or unacceptable toxicity.
干预措施: immunologic technique (Other)
Arm I
Patients receive pNGVL3-hICD vaccine admixed with GM-CSF intradermally once a month for 3 months in the absence of disease progression or unacceptable toxicity.
干预措施: immunoenzyme technique (Other)
Arm I
Patients receive pNGVL3-hICD vaccine admixed with GM-CSF intradermally once a month for 3 months in the absence of disease progression or unacceptable toxicity.
干预措施: protein expression analysis (Genetic)
Arm I
Patients receive pNGVL3-hICD vaccine admixed with GM-CSF intradermally once a month for 3 months in the absence of disease progression or unacceptable toxicity.
干预措施: biopsy (Procedure)
结局指标
主要结局
Safety as measured by NCI CTCAE v 3.0
时间窗: From baseline
Immune response
时间窗: From baseline
次要结局
- Impact of dose on immunologic response(From baseline to month 15)
- Persistence of DNA at the injection site(At 1 and 6 months after last vaccination)