A Phase 1-2 Study for Stage IV Breast and HER2/Neu Positive Cancers to Evaluate the Safety and Efficacy of a Vaccine Using Whole Cells From the SVBR- 1-GM Cell Line Genetically Engineered To Produce Granulocyte- Macrophage Colony Stimulating Factor
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 24
- 试验地点
- 3
- 主要终点
- Survival
研究概览
简要总结
RATIONALE: Vaccines made from gene-modified tumor cells may make the body build an immune response to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Interferon alfa may interfere with the growth of tumor cells. Combining vaccine therapy with cyclophosphamide and interferon alfa may kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of combining vaccine therapy with interferon alfa and cyclophosphamide in treating patients who have stage IV breast cancer.
详细描述
OBJECTIVES:
- Determine the safety, tolerability, and feasibility of vaccine therapy comprising an allogeneic (non-self) tumor cell line transfected with the sargramostim (GM-CSF) gene combined with low-dose interferon alfa and low-dose cyclophosphamide in patients with stage IV breast cancer or other solid tumors.
- Determine the clinical response, time to progression, and survival of patients treated with this regimen.
- Correlate clinical response with immunological response in patients treated with this regimen.
OUTLINE: Patients receive low-dose cyclophosphamide IV once 2-3 days before each tumor vaccine. Patients then receive tumor vaccine comprising HER2/neu-positive allogeneic (non-self) breast cancer cells transfected with the sargramostim (GM-CSF) gene intradermally (ID) on day 1. Patients also receive low-dose interferon alfa ID approximately 48 and 96 hours after each tumor vaccine. Treatment repeats every 2 weeks for 3 vaccinations and then monthly for 3 vaccinations in the absence of disease progression or unacceptable toxicity.
Patients are followed at 2 weeks and then every 3 months thereafter.
PROJECTED ACCRUAL: A total of 9-24 patients will be accrued for this study.
研究设计
- 研究类型
- Interventional
- 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
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed breast cancer meeting 1 of the following criteria:
- •Recurrent and/or metastatic lesions that are HER2/neu-positive or negative
- •Recurrent or progressive cancer of the lung, ovary, pancreas, prostate, bladder, or other primary site associated with HER2/neu-positive tumor by histochemistry
- •Bone-only metastatic breast cancer, cytologically confirmed malignant effusions, histologically confirmed marrow involvement, or other evaluable (but non-measurable) metastatic disease allowed
- •Failed prior first-line chemotherapy (e.g., anthracycline- or taxane-based therapy) with or without adjuvant chemotherapy or hormonal therapy
- •No curative or reliably effective palliative surgery, radiotherapy, or medical therapy available
- •Stable brain metastases allowed provided the following criteria are met*:
- •Previously treated
- •No concurrent requirement for corticosteroids
- •No radiological or clinical deterioration within the past 6 weeks NOTE: *Patients who had recent treatment with gamma knife or intensity-modulated radiotherapy for brain metastases are eligible provided there has been recovery from known or anticipated toxic effects
- •Patients with no HLA-A2 allele are eligible
- •Hormone receptor status:
- •Not specified
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Female or male
- •Menopausal status
- •Not specified
- •Performance status
- •Life expectancy
- •At least 4 months
- •Hematopoietic
- •Absolute granulocyte count ≥ 1,000/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Bilirubin ≤ 2 mg/dL
- •Alkaline phosphatase ≤ 5 times upper limit of normal (ULN)
- •ALT and AST ≤ 2 times ULN
- •BUN ≤ 30 mg/dL
- •Creatinine ≤ 2 mg/dL
- •≤ 1 g protein on 24-hour urine collection OR
- •≤ 1+ proteinuria on urinalysis
- •Cardiovascular
- •Hypertension controlled by agents (except beta-blockers) allowed
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •HIV negative
- •No history of anaphylactic reaction to any known or unknown antigen
- •No history of clinical hypersensitivity to sargramostim (GM-CSF), interferon, yeast, beef, or to any components used in preparation of study vaccine
- •No clinical or laboratory features indicative of AIDS
- •No rheumatological, psychiatric, or other clinically progressive major medical problems requiring treatment
- •No other malignancy within the past 2 years
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- •More than 3 weeks since prior biological therapy, including trastuzumab (Herceptin^®)
- •More than 3 weeks since prior immunotherapy
- •No concurrent immunotherapy
- •Chemotherapy
- •See Disease Characteristics
- 另有 18 项未显示
排除标准
- 未提供
结局指标
主要结局
Survival
Clinical response
Time to progression
Safety, tolerability, and feasibility
Correlation of clinical response with immunological response
次要结局
未报告次要终点