A Phase I, Non-randomized, Multiple Dose, Dose Escalation Study of the Safety, PK, PD and Efficacy of Therapeutic Vaccine, BP-GMAX-CD1, Plus Activating Agent, AP1903, in Patients With Castrate Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose of BPX-101 and AP1903
研究概览
简要总结
This is a Phase I, non-randomized, multiple-dose, 3+3 dose-escalation study of the safety, pharmacokinetics, biomarkers, preliminary efficacy and patient-reported outcomes of therapeutic vaccine, BPX-101 (formerly BP-GMAX-CD1), plus activating agent, AP1903, in patients with castrate resistant prostate cancer.
详细描述
Patients will be screened within 6 weeks prior to Week 1. A total of 3 cohorts, consisting of 3 to 6 patients each, are planned to receive five to eight intradermal (ID) injections totaling 1 mL up to 1.6mL of BPX-101 at 3 doses levels for an initial 6 doses.
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
- Male
- 接受健康志愿者
- 否
入选标准
- •Males ≥ 18 years of age
- •Histological diagnosis of adenocarcinoma of the prostate
- •Documented evidence of distant metastasis of disease
- •No more than 1 prior chemotherapeutic, biologic or combination treatment regimen (including vitamin D analogues) for CRPC. If previously treated, patients must be recovered from all toxicities prior to entry into the study.
- •Patients must have current or historical evidence of disease progression concomitant with surgical (orchiectomy) or medical castration (LHRH analogue); anti-androgen withdrawal (4 weeks for flutamide and 6 weeks for nilutamide or bicalutamide) is necessary only for patients on antiandrogens and a duration of response to antiandrogens > 3months;
- •Testosterone < 50 ng/dL achieved via medical or surgical castration. Patients receiving medical castration therapy must continue such therapy throughout the study.
- •Adequate hematologic, renal and liver function:
- •Negative serology tests for human immunodeficiency virus (HIV-1 and 2), human T-cell lymphotropic virus (HTLV-1), hepatitis B surface antigen (HBsAg) and hepatitis C (HCV)
- •Karnofsky Performance Score (KPS) ≥ 70%
- •Life expectancy > 6 months
- •Written informed consent obtained prior to the initiation of study procedures
排除标准
- •The presence of brain metastases, pleural effusions or ascites
- •Pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography > 50%), or spinal cord compression
- •A history of stage III or greater cancer, excluding prostate cancer. Basal or squamous cell skin cancers must have been adequately treated and the patient must be disease-free at the time of registration. Patients with a history of stage I or II other cancers must have been adequately treated and been disease-free for 3 years at the time of registration.
- •More than 1 prior chemotherapy, biologic or combination treatment regimen (including vitamin D analogues) for CRPC
- •Any treatment with radiopharmaceuticals, e.g. Strontium-89 and Samarium-153
- •Ketoconazole or antiandrogens (flutamide, nilutamide, bicalutamide) within 2 weeks prior to registration. Patients who demonstrate an anti-androgen withdrawal response, defined as a > 25% drop in PSA within 4 weeks (flutamide) or 6 weeks (nilutamide, bicalutamide) of stopping a non-steroidal anti-androgen, are not eligible until the PSA rises above the nadir observed after anti-androgen withdrawal.
- •Initiation of bisphosphonate therapy within 28 days prior to registration. Patients taking bisphosphonates should not have their dosing regimen altered unless medically warranted.
- •A requirement for systemic steroid or other immunosuppressive therapy for any reason.
- •Treatment with any of the following medications or interventions < 28 days prior to Screening
- •Treatment with any investigational vaccine within 2 years prior to Screening, or treatment with any other investigational product within 28 days prior to Screening
- •Any antibiotic therapy or infection within 1 week prior to Screening, including unexplained fever (temperature ≥ 100.5F or 38.1C)
- •History of autoimmune disease
- •Serious ongoing chronic or acute illness
- •Any medical intervention or other condition which, in the opinion of the Principal Investigator and/or the Bellicum Medical Monitor, could compromise adherence with study requirements
- •Other Criteria Apply however are not listed
研究组 & 干预措施
Dose escalation
Cohort 1: BPX-101, 4 x 10*6 cells administered every other week for 6 cycles Cohort 2: BPX-101, 12.5 x 10*6 cells administered every other week for 6 cycles Cohort 3: BPX-101, 25 x 10*6 cells administered every other week for 6 cycles Cohort 4: BPX-101, 25 x 10*6 cells administered every 4 weeks for 3 cycles
At 24 hours after each vaccination, a single dose of the activating agent, AP1903 for Injection, will be administered at a fixed dose of 0.4 mg/kg via intravenous (IV) infusion over 2 hours.
干预措施: BPX-101 (Biological)
Dose escalation
Cohort 1: BPX-101, 4 x 10*6 cells administered every other week for 6 cycles Cohort 2: BPX-101, 12.5 x 10*6 cells administered every other week for 6 cycles Cohort 3: BPX-101, 25 x 10*6 cells administered every other week for 6 cycles Cohort 4: BPX-101, 25 x 10*6 cells administered every 4 weeks for 3 cycles
At 24 hours after each vaccination, a single dose of the activating agent, AP1903 for Injection, will be administered at a fixed dose of 0.4 mg/kg via intravenous (IV) infusion over 2 hours.
干预措施: AP1903 (Drug)
结局指标
主要结局
Maximum tolerated dose of BPX-101 and AP1903
时间窗: 1 Year
To determine the maximum tolerated dose (MTD) of BPX-101 and AP1903 when administered 24 hours apart
Safety and tolerability of BPX-101 and AP1903
时间窗: 1 Year
To determine other measures of safety and tolerability of BPX-101 and AP1903 when administered 24 hours apart to patients with castrate resistant prostate cancer (CRPC).
次要结局
- Number of circulating tumor cells (CTC)(1 Year)
- Cancer-related pain(1 Year)
- Pain medication usage(1 Year)
- Pharmacokinetics of AP1903(1 Year)
- Immune responses and their association with clinical outcome(2 Years)
- PSA response and PSA dynamics(1 Year)
- Preliminary efficacy of BPX-101 at the maximum tolerated dose (MTD)(2 Years)