Phase 1 Study of Immunization With NY-ESO-1 Protein Combined With CpG 7909 in Patients With High-risk Stage D1 or Advanced Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Number of Patients With Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
This was a Phase 1, open-label, fixed-dose study of immunization with the NY-ESO-1 protein combined with CpG 7909 as an adjuvant in patients with histopathologically confirmed, high-risk Stage D1 or advanced prostate cancer. The primary study objective was to assess the safety of NY-ESO-1 protein/CpG 7909 immunization, and the secondary objective was to evaluate the immunity induced by immunization.
详细描述
Eligible patients received vaccinations consisting of the NY-ESO-1 protein (100 µg) combined with CpG 7909 (2.5 mg) administered intradermally every 3 weeks for 4 doses. Patients who demonstrated stable disease, minor response, partial response, or complete response at Week 13 may have continued to receive vaccinations until disease progression. In patients with mixed response, single progressive lesions may have been resected and vaccination may have been continued.
Safety was monitored continuously. Blood samples were obtained for clinical hematology, biochemistry and immune response assessments, including antinuclear antibody (ANA) and anti-dsDNA, NY-ESO-1 and/or LAGE-1 specific antibodies, and NY-ESO-1 specific cluster of differentiation (CD)4+ and CD8+ T cells.
A tumor sample, resected prior to immunization, was tested to determine NY-ESO-1 and/or LAGE-1 expression. Delayed-type hypersensitivity (DTH) testing was performed at baseline and on study.
Disease status was assessed at baseline and on study in patients with measurable disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- Male
- 接受健康志愿者
- 否
入选标准
- •Patients were eligible for enrollment if they fulfilled the following criteria:
- •High-risk Stage D1 or metastatic prostate cancer (D2), confirmed by review of histology.
- •Fully recovered from surgery.
- •Showed stable or progressive disease as assessed by X-ray, ultrasound, and/or computed tomography (CT) scans under hormonal and/or chemotherapeutic treatment, which had been administered for ≥ 3 months.
- •Any pretreatment with chemo- or radiotherapy must have been discontinued for ≥ 4 weeks prior to the first dose of study agent. Hormone therapy was allowed before and throughout the study.
- •Expected survival of ≥ 3 months.
- •Karnofsky performance status of ≥ 70%.
- •Within the last 2 weeks prior to study day 1, vital laboratory parameters should have been within the normal range, except for the following laboratory parameters, which should have been within the ranges specified:
- •Leukocytes > 3,000/µl.
- •Lymphocytes > 700/µl.
- •Platelets > 100,000/µl.
- •Serum creatinine < 2.5 mg/dL.
- •Alanine aminotransferase, aspartate aminotransferase, and total bilirubin < 2.5 x upper limit of normal.
- •Age ≥ 18 years.
- •Able to give valid written informed consent.
排除标准
- •Patients were excluded from the study if they fulfilled any of the following criteria:
- •Clinically significant heart disease (i.e., New York Heart Association Class 3 congestive heart failure; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty within the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias).
- •Other serious illnesses, e.g., active infections requiring antibiotics, bleeding disorders.
- •Concomitant systemic treatment with corticosteroids. Topical or inhalational steroids were permitted.
- •Metastatic disease to the central nervous system.
- •Mental impairment, in the opinion of the Investigator, that may have compromised the ability to give informed consent and comply with the requirements of the study.
- •Lack of availability for immunological and clinical follow-up assessments.
- •Participation in chemotherapy, radiation therapy, or any other clinical trial involving another investigational agent within 4 weeks prior to first dosing.
- •Being a recipient of an organ or bone marrow allograft. Having an autoimmune disease other than vitiligo, such as, but not limited to, inflammatory bowel disease or multiple sclerosis.
研究组 & 干预措施
NY-ESO-1 protein + CpG 7909
Patients received immunization with intradermal injections of the NY-ESO-1 protein combined with CpG 7909.
干预措施: NY-ESO-1 protein/CpG 7909 (Biological)
结局指标
主要结局
Number of Patients With Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to 56 weeks
Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, as follows: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), and Grade 5 (fatal). Adverse events (AEs) were reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, performance status evaluations, and any other medically indicated assessments, including patient interviews, from the first dose of study treatment through the final follow-up visit. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
次要结局
- Number of Patients With Cellular Antibody Response to NY-ESO-1(Up to 28 weeks)
- Number of Patients With Humoral Antibody Response to NY-ESO-1(Up to 28 weeks)
- Number of Patients With Best Tumor Response as Measured by the Response Evaluation Criteria in Solid Tumors (RECIST)(Up to 32 weeks)