Safety and Immunological Evaluation of NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine Given by Particle-mediated Epidermal Delivery (PMED) in Patients With Tumor Type Known to Express NY-ESO-1 or LAGE-1 Antigen.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 3
- 主要终点
- Number of Patients With Dose Limiting Toxicities (DLTs) and Number of Patients With Adverse Events
研究概览
简要总结
To evaluate the safety of NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine given by particle-mediated epidermal delivery (PMED) in patients with tumor types known to express NY-ESO-1 or LAGE-1.
详细描述
NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine was administered by particle-mediated epidermal delivery (PMED) at a pressure of 500 psi using the XR-1 Powderject® delivery device. The 4 microgram dosage of NY-ESO-1 was administered as 4 X 1 microgram PMEDs in close proximity. Similarly, the 8 microgram dosage was administered as 8 X 1 microgram PMEDs. The third cohort of patients received the 8 microgram dosage as a cluster dosage of 4 doses (day 1, 3, 5, 8) as 2 X 1 microgram PMEDs per day.
Blood samples were to be obtained at baseline, 2 weeks after each vaccination, prior to the second and third vaccination, and 4 weeks after the third vaccination for the assessment of clinical hematology, biochemistry measurements and immunology responses. Patients were to be evaluated for toxicity throughout the study.
Delayed-type hypersensitivity (DTH) testing was to be performed at baseline and at the 2-week visit following the first and third vaccinations.
NY-ESO-1 and/or LAGE-1 specific antibodies were to be assessed in all patients by an enzyme-linked immunosorbent assay (ELISA). NY-ESO-1 specific CD4+ and CD8+ T-cells were to be assessed in all patients by tetramer and/or ELISPOT assays.
Disease status was to be assessed at baseline and 4 weeks after the third vaccination in patients with measurable disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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 were eligible for enrollment if they fulfilled all of the following criteria:
- •Histologically proven tumor type known to express NY-ESO-1 or LAGE-1 (prostate cancer, breast cancer, bladder cancer, hepatocellular cancer, synovial sarcoma, leiomyosarcoma, head and neck, lung cancer, esophageal, ovarian, neuroblastoma); or NY-ESO-1 or LAGE-1 positive tumors determined by reverse transcriptase and polymerase chain reaction (RT-PCR) analysis, preferably, or immunohistochemistry or expression of LAGE-1 by RT-PCR.
- •Advanced disease and have declined, delayed, failed or completed standard therapy.
- •Full recovery from surgery.
- •Expected survival of at least 6 months.
- •Karnofsky performance scale ≥
- •Adequate bone marrow, kidney, liver and immune functions.
- •Able and willing to give valid written informed consent.
排除标准
- •Clinically significant heart disease (NYHA Class III or IV).
- •Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders, clinically significant liver or renal insufficiency requiring treatment.
- •Patients with serious intercurrent illness, requiring hospitalization.
- •Known HIV, Hepatitis B or Hepatitis C positivity.
- •History of autoimmune diseases (e.g. SLE, scleroderma). Vitiligo is not an exclusion criterion.
- •Concomitant systemic treatment with corticosteroids, anti-histaminic drugs or non-steroidal anti-inflammatory drugs. Specific COX-2 inhibitors are permitted. Low dose aspirin is permitted. Topical or inhalational steroids are permitted.
- •Evidence of skin disease (e.g. psoriasis, eczema or keloid formation) at the proposed administration site.
- •Allergy to gold (including gold jewelry).
- •History or evidence of chrysotherapy (gold salts).
- •Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to first dosing (6 weeks for nitrosoureas).
- •Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer, cervical carcinoma in situ.
- •Mental impairment, in the opinion of the investigator, that may compromise 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 any other clinical trial involving another investigational agent within 4 weeks prior to first dosing.
- •Pregnancy or breastfeeding.
- •Women of childbearing potential: Refusal or inability to use effective means of contraception.
结局指标
主要结局
Number of Patients With Dose Limiting Toxicities (DLTs) and Number of Patients With Adverse Events
时间窗: up to 13 weeks
All adverse events were graded according to the National Cancer Institute Common Toxicity Criteria (CTC) Scale (Version 3.0, published June 10, 2003). DLT was defined as * ≥ Grade 2 autoimmune phenomena * Asymptomatic bronchospasm or generalized urticaria * Grade ≥ non hematological toxicities (including injection site reactions) * Grade ≥ 3 hematological toxicities A dose-limiting adverse event must be definitely, probably, or possibly related to the administration of the investigational agent and must occur between first dose and 4 weeks after the last dose.
次要结局
- Number of Patients With Tumor Response According to the Response Evaluation Criteria in Solid Tumors (RECIST).(13 weeks)
- Number of Patients With NY-ESO-1-Specific Humoral Immunity as Determined by an Increase in Antibody Titer From Baseline.(up to 13 weeks)
- Number of Patients With Delayed-Type Hypersensitivity (DTH) Skin Reactions to NY-ESO-1 Protein(Up to 11 weeks)
- Number of Patients With NY-ESO-1-Specific Cellular Immunity as Measured by an Increase in NY-ESO-1-Specific CD4+ and CD8+ T-Cells Following Treatment.(up to 13 weeks)