Phase II Study of Recombinant Vaccinia-NY-ESO-1 (rV-NY-ESO-1) and Recombinant Fowlpox-NY-ESO-1 (rF-NY-ESO-1) in Patients With Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma Whose Tumors Express NY-ESO-1 or LAGE-1 Antigen
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 2
- 主要终点
- Percentage of Patients in Remission at 1 Year
研究概览
简要总结
This was a Phase 2, single-center, open-label study of recombinant vaccinia-NY-ESO-1 (rV-NY-ESO-1) and recombinant fowlpox-NY-ESO-1 (rF-NY-ESO-1) injections in patients who had a complete response to standard therapy for epithelial ovarian, fallopian tube, or primary peritoneal carcinoma and whose tumors expressed NY-ESO-1 or LAGE-1 antigen. Study objectives were to evaluate maintenance of remission at 12 months, time to failure of vaccine therapy, cellular and humoral immunity and any correlation with time to failure, and safety.
详细描述
Patients received a single intradermal injection of rV-NY-ESO-1 (3.1 × 10^7 plaque forming units [PFU]) on Day 1, followed by monthly subcutaneous injections of rF-NY-ESO-1 (7.41 × 10^7 PFU) for 6 months (Days 29, 57, 85, 113, 141, and 169) or until observation of treatment-related ≥ grade 3 toxicity or disease progression. Study injections were administered during a 28-week evaluation period. Patients returned to the clinic for follow-up on Day 197 (i.e., 28 days after the last study injection) and every 2 months thereafter for at least 12 months. In patients with measurable disease, tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Patients were monitored continuously for safety for the duration of study participation.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Histologically documented epithelial carcinoma arising in the ovary, fallopian tube, or peritoneum, from stage II to IV at diagnosis.
- •Received initial surgery and chemotherapy with at least one platinum-based chemotherapy regimen.
- •Demonstrated complete response to first line therapy as evidenced by negative clinical examination, cancer antigen (CA)-125 tumor marker, and computed tomography (CT) scan. In addition, if second-look surgery was performed, patients must have had no evidence of microscopic or macroscopic disease. Patients must have been within 6 months of completing their first line platinum-based chemotherapy. These patients would normally enter a period of observation as standard management.
- •Tumor expression of 1) NY-ESO-1 by reverse transcription-polymerase chain reaction (RT-PCR) analysis, preferably, or immunohistochemistry; or 2) LAGE-1 by RT-PCR.
- •Expected survival of at least 6 months.
- •Full recovery from surgery.
- •Karnofsky performance status of 70% or more.
- •Patients must have had the following clinical laboratory results:
- •neutrophil count: ≥ 1.5 x 10^9/L
- •lymphocyte count: ≥ 0.5 x 10^9/L
- •platelet count: ≥ 100 x 10^9/L
- •serum creatinine: ≤ 2 mg/dL
- •serum bilirubin: ≤ 2 mg/dL
- •Ability to avoid close contact with children < 3 years of age; pregnant or breast feeding women; individuals with active, or a history of, eczema or atopic dermatitis or other skin disorders such as burns, chickenpox, shingles, impetigo, herpes, severe acne, or psoriasis; and immunocompromised individuals (human immunodeficiency virus [HIV], leukemia, lymphoma, solid organ transplantation, generalized malignancy, cellular or humoral immunodeficiency syndromes, patients currently receiving cytotoxic chemotherapies, radiation, or high dose corticosteroids).
- •Have been informed of other treatment options.
- •Age ≥ 18 years.
- •Able and willing to give valid written informed consent.
排除标准
- •Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may have been available.
- •Other serious illnesses (eg, serious infections requiring antibiotics, bleeding disorders).
- •History of current eczema or atopic dermatitis.
- •History of autoimmune disease (eg., thyroiditis, lupus).
- •Other acute, chronic, or exfoliative skin conditions such as burns, chickenpox, shingles, impetigo, herpes, severe acne, or psoriasis.
- •Concomitant systemic treatment with corticosteroids, anti-histamine or non-steroidal anti-inflammatory drugs. Specific cyclooxygenase-2 inhibitors were permitted.
- •Chemotherapy, radiation therapy, or immunotherapy within 4 weeks before study entry (6 weeks for nitrosoureas).
- •Known HIV positivity.
- •Known allergy or severe reaction to a smallpox (vaccinia) vaccination.
- •Known allergy to eggs, determined by history.
- •Myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, chest pain or shortness of breath with activity, or other heart conditions being treated by a doctor.
- •Presence of 3 or more of the following risk factors:
- •Hypertension
- •Hypercholesterolemia
- •A first degree relative (for example, mother, father, brother, sister) who had a heart condition before the age of 50
- •Current cigarette smoker
- •Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.
- •Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study.
- •Lack of availability of a patient for immunological and clinical follow-up assessment.
结局指标
主要结局
Percentage of Patients in Remission at 1 Year
时间窗: 12 months
Time to failure (TTF) was evaluated as the crude proportion of patients in remission at 1 year, calculated as: 100 x (number of patients in remission at 1 year)/(number of patients with known status at 1 year). The Kaplan-Meier cumulative estimate of the proportion of patients in remission at 1 year was also calculated.
次要结局
- Mean Absolute Cancer Antigen-125 Values Over Time on Study(Up to 20 months)
- Number of Patients With Detectable T-cell Responses Following Vaccination(Up to 20 months)
- Number of Patients With Best Overall Tumor Response(Up to 20 months)
- Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity(Up to 20 months)
- Number of Patients With Treatment-emergent Adverse Events(Continuously for up to 20 months)
- Mean Time to Failure Among Patients Who Progressed On Study(Up to 20 months)
- Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens(Up to 20 months)
- Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination(Up to 6 months)