A Phase I Study of an MVA Vaccine Targeting P53 in Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Safety and tolerance of modified vaccinia virus ankara vaccine expressing p53 assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4 toxicity scale
研究概览
简要总结
RATIONALE: Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with colorectal, stomach, or pancreatic cancer.
详细描述
PRIMARY OBJECTIVES:I. To establish whether 2 vaccine dose levels of modified vaccinia virus ankara vaccine expressing p53 (MVAp53) vaccines are safe and well tolerated in patients with p53 over-expressing solid tumor malignancy.
SECONDARY OBJECTIVES:I. To provide preliminary evidence of enhanced cellular and humoral immunity to p53.
OUTLINE:This is a phase I, dose-escalation trial of modified vaccinia virus ankara vaccine expressing p53 (MVAp53).Patients receive MVAp53 subcutaneously (SC) on days 0, 21, and 42 in the absence of unacceptable toxicity.
After completion of study treatment, patients are followed up annually for 5 years.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with unresectable and chemotherapy resistant primary or recurrent carcinoma of colorectal, gastric or pancreatic origin
- •There must be pathologic evidence for malignancy with a soft tissue component of tumor evident on CT scan imaging or physical examination
- •Patient must be able to give informed consent
- •There must be an anticipated survival of at least 3 months
- •Performance status of 80-100 (Karnofsky performance status)
- •WBC count >= 3,000uL
- •Platelet count >= 100,000uL
- •Prothrombin time and partial thromboplastin time of <= 1.5 times the upper limit of normal
- •Women of childbearing potential must have a negative pregnancy test; women and men of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant during or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
- •Patients with asymptomatic small volume bone disease not likely to require radiation therapy during the period of the vaccine trial will be eligible
- •Hemoglobin level > 9g/dL
- •There must be evidence of p53 over expression by immunohistochemistry with > 10% of cells within the tumor strongly positive
- •Patients with colorectal cancer will need to have failed to respond to 5-FU based therapy with oxaliplatin, irinotecan as well as epidermal growth factor receptor (EGFR) directed therapies (if appropriate); patients with gastric cancer will need to have progressed on standard first line chemotherapy or chemoradiotherapy and Herceptin based therapy (if appropriate); patients with pancreatic cancer who have failed to respond to at least 1 chemotherapy regimen
排除标准
- •Diagnosis which has been associated with immunodeficiency, including HIV
- •Prior radiation to more than 50% of all nodal groups
- •Concurrent use of corticosteroids
- •History of another malignancy, other than nonmelanoma skin cancer in the past 2 years
- •Recent major surgery
- •Serious intercurrent illness
- •Temperature >= 101F within 3 days prior to the initial injection
- •Pregnancy or lactation
- •Clinically evident brain metastasis
- •Autoimmune disease
- •HIV seropositivity or refusal to hear the results of the HIV test
- •Receipt of organ grafts
- •History of severe environmental allergies
- •History of severe neurological, cardiovascular, renal, hepatic, endocrine, respiratory, or bone marrow dysfunction requiring frequent re-evaluation, and management by a physician
- •Patients with a history of congestive heart failure or coronary artery disease which has not been resolved by bypass or stent
- •History of myopericarditis
- •Known family history of Li-Fraumeni syndrome
- •Allergy to egg proteins
- •Chemotherapy or radiation within the 4 weeks preceding enrollment
研究组 & 干预措施
Treatment (vaccine therapy)
Patients receive MVAp53 subcutaneously on days 0, 21, and 42 in the absence of unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Treatment (vaccine therapy)
Patients receive MVAp53 subcutaneously on days 0, 21, and 42 in the absence of unacceptable toxicity.
干预措施: enzyme-linked immunosorbent assay (Other)
Treatment (vaccine therapy)
Patients receive MVAp53 subcutaneously on days 0, 21, and 42 in the absence of unacceptable toxicity.
干预措施: flow cytometry (Other)
Treatment (vaccine therapy)
Patients receive MVAp53 subcutaneously on days 0, 21, and 42 in the absence of unacceptable toxicity.
干预措施: immunoenzyme technique (Other)
Treatment (vaccine therapy)
Patients receive MVAp53 subcutaneously on days 0, 21, and 42 in the absence of unacceptable toxicity.
干预措施: modified vaccinia virus ankara vaccine expressing p53 (Biological)
结局指标
主要结局
Safety and tolerance of modified vaccinia virus ankara vaccine expressing p53 assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4 toxicity scale
时间窗: Assessed up to 12 months
Safety data for each administered dose will be summarized using descriptive numbers and 95% confidence intervals from the exact binomial distributions
次要结局
- Immunogenicity(Assesse up to 12 months)