A Phase 1 Study of NY-ESO-1 Overlapping Peptides With or Without Immunoadjuvants Montanide and Poly-ICLC Vaccination of Epithelial Ovarian Cancer, Fallopian Tube, or Primary Peritoneal Cancer Patients in Second or Third Remission
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 2
- 主要终点
- Overview of Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
This was a Phase 1, open-label study of repeated vaccination with NY-ESO-1 overlapping peptides (OLP4) with or without the immunoadjuvants Montanide and polyinosinic-polycytidylic acid - poly-L-lysine carboxymethylcellulose (poly-ICLC) administered every 3 weeks for a total of 5 vaccinations in subjects with epithelial ovarian, fallopian tube, or primary peritoneal cancer in second or third clinical remission. Study objectives included determination of the safety and immunogenicity following vaccination.
详细描述
Subjects received NY-ESO-1 OLP4 by subcutaneous injection once every 3 weeks (Weeks 1, 4, 7, 10, and 13) for a total of 5 vaccinations.
Subjects were assigned sequentially to 1 of 3 dosing cohorts:
Cohort 1: received NY-ESO-1 OLP4 alone; Cohort 2: received NY-ESO-1 OLP4 in combination with Montanide; Cohort 3: received NY-ESO-1 OLP4 in combination with Montanide and Poly-ICLC.
Enrollment into each subsequent dosing cohort was dependent on a dose-limiting toxicity (DLT) rate of <33% in the preceding cohort. No dose escalation was planned.
Subjects were observed by study staff for up to 30 minutes following each vaccination. Immunologic assessments were performed prior to the first vaccination and 3 weeks after each vaccination. Toxicity assessments were performed with each vaccination and 3 weeks after the completion of therapy (ie, the final study visit was Week 16). Immunologic assessments included measurement of the anti-NY-ESO-1 antibody by enzyme-linked immunsorbent assay (ELISA), detection of CD-4 and CD-8 cellular responses by tetramer and enzyme-linked immunosorbent spot assay (ELISPOT), and delayed-type hypersensitivity (DTH).
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
- 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, stage II to IV at diagnosis, and post-initial cytoreductive surgery and chemotherapy with at least one platinum-based chemotherapy regimen.
- •In second or third stable complete clinical remission, defined as a) stable cancer antigen (CA)-125 < 35 U/ml (defined as CA-125 that had not doubled from the post chemotherapy nadir), b) unremarkable physical examination, and c) no definite evidence of disease by computed tomography (CT) of the abdomen and pelvis. Lymph nodes and/or soft tissue abnormalities ≤ 1.0 cm that are often present in the pelvis were not considered definite evidence of disease.
- •Expected survival of at least 4 months.
- •Karnofsky performance scale ≥ 70%.
- •Laboratory values within the following limits:
- •Hemoglobin ≥ 10.0 g/dL
- •Neutrophil count ≥ 1.5 x 10^9/L
- •Platelet count ≥ 80 x 10^9/L
- •Serum creatinine ≤ 2.0 mg/dL
- •Serum bilirubin ≤ 2.5 x institutional upper limit of normal (ULN)
- •aspartate aminotransferase/alanine aminotransferase ≤ 2.5 x institutional ULN
- •Age ≥ 18 years.
- •≥ 4 weeks since completion of prior cytotoxic chemotherapy.
- •Able and willing to give valid written informed consent
排除标准
- •Clinically significant heart disease (New York Heart Association Class III or IV).
- •Serious intercurrent illness, eg, serious infections requiring prolonged parenteral antibiotics or bleeding disorders requiring hospitalization.
- •Positive stool guaiac excluding hemorrhoids.
- •Known autoimmune disease (ie, rheumatoid arthritis, ulcerative colitis, etc); or immune deficiency (human immunodeficiency virus, hypogammaglobulinemia); or known active infections with Hepatitis B or Hepatitis C; or receipt of immunosuppressive drugs such as systemic corticosteroids or cyclosporin, etc.
- •Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ.
- •History of previous severe allergic reactions to vaccines or unknown allergens.
- •Mental impairment 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 any other clinical trial involving another investigational agent within 4 weeks prior to first dose of study agent.
- •Pregnancy or breast-feeding.
- •Women of childbearing potential: Refusal or inability to use effective means of contraception.
结局指标
主要结局
Overview of Treatment-emergent Adverse Events (TEAEs)
时间窗: Continuously for up to 16 weeks
Analysis of TEAEs reported from clinical laboratory tests, physical examinations, and vital signs from pre-treatment through 3 weeks after the last dose of study treatment.
次要结局
- Cancer Antigen (CA)-125 Levels Up to 16 Weeks Post-Baseline(Screening, Week 7, and Week 16)
- Number of Patients With Delayed-type Hypersensitivity (DTH) Reactions (Induration and Redness) to NY-ESO-1 OLP4 at Screening and Week 16(Screening and Week 16)
- Number of Patients With Detectable Serum Immunoglobulin G (IgG) Antibody Titers Against NY-ESO-1 Up to 16 Weeks Post-Baseline(Screening and Weeks 4, 7, 10, 13, and 16)
- Tumor Measurement Results According to the Response Evaluation Criteria for Solid Tumors (RECIST) Up to 16 Weeks Post-Baseline(Screening and every 2 months up to Week 16)
- Number of Patients With Detectable CD8+ and CD4+ T-cell Responses Up to 16 Weeks Post-Baseline(Screening and Weeks 4, 7, 10, 13, and 16)