A Phase I Trial of the Safety and Immunogenicity of a Multi-epitope HER-2/Neu Peptide Vaccine in Subjects Previously Treated for HER-2 Positive Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 22
- 试验地点
- 2
- 主要终点
- Proportion of patients who experience toxicities of attribution during the course of treatment (grades 3-5 of the NCI's Cancer Therapy Evaluation Program [CTEP] Common Terminology Criteria for Adverse Events, version 4.0) for 2 years.
研究概览
简要总结
The purpose of this study is to look at the safety and immune response to a vaccine used in patients previously treated for HER2 (human epidermal growth factor receptor 2) positive breast cancer.
详细描述
PRIMARY OBJECTIVES:
I. To determine the safety profile of a peptide-based vaccine targeting HER-2/neu, in patients with stage II/III HER-2 positive breast cancer.
II. To determine the ability of this vaccination protocol to elicit an immune response as measured by activated HER-2/neu-specific T lymphocytes or high-affinity antibodies.
SECONDARY OBJECTIVES:
I. To compile descriptive follow-up data regarding vital status and disease recurrence.
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
- •Histological confirmation of primary breast cancer, stage II or III, completely resected; Note: history of a local recurrence allowable if also completely resected
- •Prior diagnosis of HER-2 positive primary breast cancer using American Society of Clinical Oncologists (ASCO)/College of American Pathologists (CAP) guidelines (either by evidence of 3+ immunohistochemical staining or with in situ hybridization [FISH] amplification)
- •Completion of surgery +/- radiation at least 30 days prior to registration
- •Must have received mastectomy or lumpectomy plus radiation
- •Must have received either neoadjuvant and/or adjuvant chemotherapy for treatment of breast cancer
- •Must have received either neoadjuvant and/or adjuvant trastuzumab for treatment of breast cancer
- •All chemotherapy, trastuzumab, and/or corticosteroids must be completed at least 90 days prior to registration; Note: hormonal therapy and bisphosphonates may be ongoing
- •Clinically without any evidence of disease recurrence/progression (per practice guidelines for breast cancer)
- •Absolute neutrophil count (ANC) >= 1500/mm^3
- •Platelet count >= 75,000/mm^3
- •Hemoglobin >= 9.0 g/dL
- •Creatinine =< 2 x upper limit of normal (ULN)
- •Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2 x ULN
- •Albumin >= 3 g/dL
- •Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
- •Capable of understanding the investigative nature, potential risks, and benefits of the study
- •Capable of providing valid informed consent
- •Willing to return to enrolling institution (Mayo Clinic Rochester) for all study visits (immunizations, blood draws, etc)
- •Willing to employ adequate contraception from the time of registration through 6 months after the final vaccine cycle; Note: adequate contraception methods include birth control pills, barrier device, intrauterine device
- •Willing to provide blood samples for correlative research purposes
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
- •Willing to receive a tetanus vaccination if you have not had one within the past year
排除标准
- •Any prior lapatinib or pertuzumab treatment
- •Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
- •Pregnant women
- •Nursing women unwilling to stop breast feeding
- •Men or women of child bearing potential who are unwilling to employ adequate contraception from the time of registration through 6 months after the final vaccine cycle Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens Immunocompromised patients including patients known to be human immunodeficiency virus (HIV) positive or those on chronic steroids; Note: must be off systemic steroids at least 90 days prior to registration; topical steroids or steroid eye drops are permitted Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Uncontrolled acute or chronic medical conditions including, but not limited to the following:
- •Active infection requiring antibiotics
- •Congestive heart failure with New York Heart Association class III or IV; moderate to severe objective evidence of cardiovascular disease
- •Myocardial infarction or stroke within previous 6 months Receiving any other investigational agent Other active malignancy at time of registration or within the last three years prior to registration; EXCEPTIONS: non-melanoma skin cancer or carcinoma-in-situ (eg of cervix, prostate); NOTE: if there is a history of prior malignancy, they must not be receiving other specific treatment (cytotoxics, monoclonal antibodies, small molecule inhibitors) for their cancer Known history of autoimmune disease, including Type I diabetes Any prior hypersensitivity or adverse reaction to granulocyte-macrophage colony-stimulating factor (GM-CSF) History of trastuzumab-related cardiac toxicity requiring interruption or discontinuation of therapy, even if left ventricular ejection fraction (LVEF) fully recovered Baseline LVEF with a value below 55% Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment History of myocardial infarction =< 168 days (6 months) prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias Bilateral invasive breast cancer, either synchronous or metachronous; Note: ductal carcinoma in situ in the contralateral breast is permissible
研究组 & 干预措施
Treatment (HER-2/neu peptide vaccine)
Patients receive HER-2/neu peptide vaccine ID every 28 days for up to 6 courses in the absence of disease recurrence or unacceptable toxicity.
干预措施: HER-2/neu peptide vaccine (Biological)
Treatment (HER-2/neu peptide vaccine)
Patients receive HER-2/neu peptide vaccine ID every 28 days for up to 6 courses in the absence of disease recurrence or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Proportion of patients who experience toxicities of attribution during the course of treatment (grades 3-5 of the NCI's Cancer Therapy Evaluation Program [CTEP] Common Terminology Criteria for Adverse Events, version 4.0) for 2 years.
时间窗: Assessed up to 2 years following final immunization
The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.
To determine the ability of this vaccination protocol to elicit an immune response as measured by activated HER-2/neu-specific T lymphocytes or high-affinity antibodies
时间窗: 30 months
Immune responses to to the vaccine components will be periodically assessed using various assays measuring cytokine release, frequency of T cells, and antibody generation.
次要结局
- Disease-free survival(30 months)