Phase I, Open-label Trial to Evaluate the Safety and Immunogenicity of INO-5150 Alone or in Combination With INO-9012 in Men With Biochemically Relapsed (PSA) Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 62
- 试验地点
- 19
- 主要终点
- Antigen specific immune response of INO-5150 alone or with INO-9012 delivered via IM EP
研究概览
简要总结
This is a phase I, open-label trial to evaluate the safety and immunogenicity of INO 5150 alone or in combination with INO-9012 when delivered intramuscularly (IM) followed by electroporation (EP) in men with biochemically relapsed prostate cancer.
详细描述
Phase I, open label study of INO-5150 (DNA plasmids encoding prostate specific antigen (PSA) and prostate specific membrane antigen (PSMA)) alone or co-administered with INO-9012 (IL-12 plasmid) delivered intramuscularly followed by EP using the CELLECTRA®-5P device in adult males with biochemically relapsed prostate cancer following definitive local therapy (e.g. prostatectomy, external beam radiation, or brachytherapy). Four injections will be administered to approximately 60 eligible subjects who consent to participate in the study. Subjects will be monitored for safety and immunogenicity through Week 72.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Men aged 18 to 90 years with a histologic diagnosis of prostate cancer;
- •c. Biochemical recurrence following local therapy, either surgery or radiation. Rising PSA defined as:
- •After definitive surgery, e.g.
- •After radical prostatectomy, two PSA measurements of ≥ 1.0 ng/mL at least one week apart;
- •After cryosurgery, two PSA measurements of ≥ 2.0 ng/mL at least one week apart;
- •Other definitive surgical procedures may be permissible upon the approval of the medical monitor OR
- •After radiation therapy (e.g., external beam radiation, brachytherapy, or salvage/adjuvant radiation therapy after surgery), two post radiation PSA measurements level of nadir plus 2.0 ng/mL at least one week apart.;
- •Serum testosterone level:
- •i) Subjects with no history of androgen deprivation therapy:
- •A single measurement greater than 150 ng/dL or 5.2 nmol/L within 3 months of enrollment
- •ii) Subjects with a history of androgen deprivation therapy (either in adjuvant or biochemical relapse setting):
- •The two most recent measurements of serum testosterone prior to enrollment must fulfill the following criteria:
- •Both measurements are greater than 150 ng/dL or 5.2 nmol/L;
- •The two measurements are spaced at least 14 days apart;
- •Both must be measured within 3 months of enrollment;
- •Normal electro cardio gram (ECG) or ECG with no clinically significant findings;
- •Adequate bone marrow, hepatic, and renal function tests within 30 days prior to enrollment:
- •CBC (except platelets and hemoglobin), serum chemistry, liver panel, and CPK values ≤ Grade 1 abnormality as defined in CTCAE v 4.03 dated June 14, 2010
- •Platelets ≥ 75,000 /mL;
- •Hemoglobin ≥ 9.0 g/dL;
- •No desire or plans to father new children during the study and/or have a prior vasectomy
排除标准
- •PSA doubling time (PSA-DT) of ≤ 3 months, using 2 PSA values at least 4 weeks apart, calculated according to the Memorial Sloan-Kettering Cancer Center nomogram (https://www.mskcc.org/nomograms/prostate/psa-doubling-time);
- •Clinical or radiologic evidence of distant metastatic disease other than small volume (<1.5 cm) nodes, this should be tested within 12 months from enrollment;
- •Receipt of investigational therapy in a clinical trial setting within 30 days of enrollment;
- •Any pre-excitation syndromes, e.g., Wolff-Parkinson-White syndrome;
- •Prior major surgery or radiation therapy within 4 weeks of enrollment;
- •Any prior chemotherapy, except short-course neo-adjuvant or adjuvant chemotherapy that had been stopped for at least 6 weeks prior to Study enrollment;
- •Active AIDS / HIV infection, clinically uncontrolled immune deficiency disorders;
- •Clinically uncontrolled autoimmune disorders, transplant recipients who depend on immunosuppressive therapy, other immunosuppressive conditions including any concurrent condition requiring immunosuppressive/immunomodulating agents;
- •Recipient of any blood product and immunotherapy (such as anti-PD1, anti-PDL-1 and anti-CTLA4) within 3 months of enrollment;
研究组 & 干预措施
Arm B
8.5mg INO-5150 and electroporation device CELLECTRA®-5P
干预措施: Electroporation using CELLECTRA®-5P (Device)
Arm A
2mg INO-5150 and electroporation device CELLECTRA®-5P
干预措施: 2mg INO-5150 and electroporation device CELLECTRA®-5P (Biological)
Arm A
2mg INO-5150 and electroporation device CELLECTRA®-5P
干预措施: Electroporation using CELLECTRA®-5P (Device)
Arm B
8.5mg INO-5150 and electroporation device CELLECTRA®-5P
干预措施: 8.5mg INO-5150 and electroporation device CELLECTRA®-5P (Biological)
Arm C
2mg INO-5150 plus 1mg INO-9012 and electroporation device CELLECTRA®-5P
干预措施: 2mg INO-5150 plus 1mg INO-9012 and electroporation device CELLECTRA®-5P (Biological)
Arm C
2mg INO-5150 plus 1mg INO-9012 and electroporation device CELLECTRA®-5P
干预措施: Electroporation using CELLECTRA®-5P (Device)
Arm D
8.5mg INO-5150 plus 1mg INO-9012 and electroporation device CELLECTRA®-5P
干预措施: 8.5mg INO-5150 plus 1mg INO-9012 and electroporation device CELLECTRA®-5P (Biological)
Arm D
8.5mg INO-5150 plus 1mg INO-9012 and electroporation device CELLECTRA®-5P
干预措施: Electroporation using CELLECTRA®-5P (Device)
结局指标
主要结局
Antigen specific immune response of INO-5150 alone or with INO-9012 delivered via IM EP
时间窗: 72 weeks
Antigen specific cellular immune responses
Safety and tolerability of INO-5150 alone or with INO-9012 delivered via IM EP ( Incidence of adverse events, Injection site reactions, Changes in safety laboratory parameters)
时间窗: 72 weeks
1. Incidence of adverse events (all, severe, \[NCI CTCAE v4.03\] and serious) classified by system organ class (SOC), preferred term, severity, and relationship to study medication and schedule 2. Injection site reactions 3. Changes in safety laboratory parameters .
次要结局
- PSA response rate by PSA testing(72 weeks)