A Phase I Study of Concomitant WT1 Analog Peptide Vaccine or NY-ESO-1 Overlapping Peptides Vaccine in Combination With Nivolumab in Patients With Recurrent Ovarian Cancer Who Are in Second or Greater Remission
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 6
- 主要终点
- Dose limiting toxicity (DLT)
研究概览
简要总结
The purpose of this study is to test the safety of a combination of an investigational WT1 vaccine and another drug called nivolumab. This is the first time that the WT1 vaccine and nivolumab are being used in combination. Also, to test the safety of a combination of an investigational NY-ESO-1 vaccine and another drug called nivolumab.
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
- •Pathologic diagnosis of ovarian, fallopian tube or primary peritoneal cancer confirmed by pathology review at MSK.
- •Patients will have relapsed at least once and returned to complete clinical remission after additional chemotherapy. Interval surgery is permitted.
- •Complete clinical remission is defined as CA-125 within normal limits, examination and CT or MRI without objective evidence of disease (non specific abnormalities are permitted on radiologic imaging).
- •Patients may sign screening consent during recurrence or at time of remission if they can start vaccine therapy within 4 months of completing chemotherapy.
- •Testing of patient's archived (paraffin embedded, unstained slides) or freshly biopsied tumor nodules must be positive for WT1 (Cohort 1) or NY-ESO-1 (Cohort 2) protein expression. WT1 expression: Immunohistochemical analysis will be performed using the technique described by Dupont et al [58]. WT1 expression will be graded according to an adaptation of the German Immunoreactive Score (IRS). Only tumors with moderate to strong IRS scores (4-12) will be considered WT1 positive.
- •NY-ESO-1 expression: Tissue available from primary and/or recurrent disease will be evaluated for tumor expression of NY-ESO-1 by immunohistochemical (IHC) and/or RT-PCR analysis will be performed using the technique described by Jungbluth et al
- •Age ≥ 18 years
- •Karnofsky performance status ≥ 70%
- •Hematologic parameters: Absolute neutrophil count ≥ 1000/mcL, Platelets > 50 K/mcL.
- •Biochemical parameters: Total bilirubin ≤ 1.5 mg/dl, AST and ALT ≤ 2.5 x upper limits of normal, Creatinine ≤ 1.5 mg/dl.
- •Patient of childbearing potential must have a negative serum pregnancy test prior to study entry and must be practicing and effective form of birth control
排除标准
- •Pregnant or lactating women
- •Patients with active infection requiring systemic antibiotics, antiviral, or antifungal treatments
- •Patients with a serious unstable medical illness or another active cancer.
- •Patients with a condition requiring systemic treatment with either corticosteroids (>10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses >10mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- •Patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
- •Patients with known active hepatitis B virus or hepatitis C virus acute or chronic infection.
- •Patients with active known or suspected autoimmune disease (treated hypothyroidism is permitted to enroll)
- •Patients with active interstitial pneumonitis.
研究组 & 干预措施
WT1 Vaccine and Nivolumab
Patients will initially receive 6 vaccinations over 12 weeks and 7 infusions of nivolumab every two weeks over 14 weeks. Toxicity assessments will be performed with each dose of vaccine, and 3 weeks after the completion of therapy at week 15. Patients who do not have disease progression at the week 15 evaluation are permitted to receive 4 additional vaccines administered approximately every 8 weeks. This maintenance vaccine course would begin at week 19.This cohort has completed recruitment.
干预措施: WT1 Vaccine (Biological)
WT1 Vaccine and Nivolumab
Patients will initially receive 6 vaccinations over 12 weeks and 7 infusions of nivolumab every two weeks over 14 weeks. Toxicity assessments will be performed with each dose of vaccine, and 3 weeks after the completion of therapy at week 15. Patients who do not have disease progression at the week 15 evaluation are permitted to receive 4 additional vaccines administered approximately every 8 weeks. This maintenance vaccine course would begin at week 19.This cohort has completed recruitment.
干预措施: Nivolumab (Drug)
ESO-1 Vaccine and Nivolumab
Patients will be vaccinated with the NY-ESO-1 OLP4 vaccine. Patients will receive a 1.0 mL emulsion of NY-ESO-1 OLPs with Poly-ICLC and Montanide.Nivolumab will be administered intravenously as a 30-minute infusion per institutional guidelines on weeks 0, 2, 4, 6, 8, 10 and 12.
干预措施: Nivolumab (Drug)
ESO-1 Vaccine and Nivolumab
Patients will be vaccinated with the NY-ESO-1 OLP4 vaccine. Patients will receive a 1.0 mL emulsion of NY-ESO-1 OLPs with Poly-ICLC and Montanide.Nivolumab will be administered intravenously as a 30-minute infusion per institutional guidelines on weeks 0, 2, 4, 6, 8, 10 and 12.
干预措施: NY-ESO-1 Vaccine (Biological)
结局指标
主要结局
Dose limiting toxicity (DLT)
时间窗: 30 days
The first 3 patients will be observed for 30 days before enrolling the next 7 patients. Accrual will continue as patients become available after the first 3 patients are observed for 30 days. If \>2/10 DLTs are observed then the study combination will not be considered safe.
次要结局
- immune response (cohort 2)(week 15)
- progression-free survival rate (cohort 2)(1 year)