NCT01337518暂停1 期
A Phase 1a/1b, Open-Label Study Evaluating the Safety and Tolerability of EZN-4176, an Androgen Receptor mRNA Antagonist, in Adult Patients With Castration-Resistant Prostate Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 暂停
- 入组人数
- 150
- 试验地点
- 2
- 主要终点
- Determine the Maximum Tolerated Dose (MTD) of EZN-4176 administered as a weekly 1-hour IV infusion.
研究概览
简要总结
This study will evaluate an experimental drug called EZN-4176 to determine the anticancer effects when it is given to patients with an advanced form of prostate cancer called castration-resistant prostate cancer (CRPC). Goals of this phase I study include finding out the dose of EZN-4176 that can be safely given without serious side effects and to determine the amount of EZN-4176 that should be given in future studies.
详细描述
This study will be conducted in two phases:
- Phase 1a will involve dose escalation to determine the maximum tolerated dose (MTD). The MTD will be determined on the basis of the results from the safety evaluation.
- Phase 1b will involve cohort expansion at one or more dose levels to determine the recommended Phase 2 dose. The recommended Phase 2 dose, which may differ from the MTD, will be determined on the basis of results from safety, activity, and pharmacologic and correlative studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Capable of understanding protocol requirements & risks & providing written informed consent
- •Histologically or cytologically confirmed diagnosis of metastatic prostate adenocarcinoma
- •Ongoing gonadal androgen-deprivation therapy with LHRH analogs or orchiectomy. Patients without orchiectomy must receive effective LHRH analog therapy during the study
- •Testosterone < 50 ng/dL
- •Progressive disease after androgen deprivation - with all 3 of the following criteria:PSA evidence of progressive prostate cancer; PSA ≥ 5 ng/mL increasing on at least 2 successive occasions, at least 2 weeks apart. If confirmatory PSA < screening PSA, additional test for increasing PSA is needed
- •Patients receiving anti-androgen agent as part of primary androgen ablation: disease progression after stopping the anti-androgen agent. This disease progression is defined: 2 consecutive increasing PSAs ≥ 2 weeks apart, or documented osseous or soft tissue progression. Flutamide patients: at least one of the PSAs ≥ 4 weeks after stopping flutamide. Bicalutamide or nilutamide patients: at least one PSA ≥ 6 weeks after stopping the anti-androgen agent.
- •Patients who failed standard therapy or who, after physician discussion, wish to delay chemotherapy
- •Age ≥ 18 yrs
- •ECOG Score: 0-1
- •Albumin ≥3.0 g/dL
- •ANC ≥ 1,500/µL
- •Plts ≥ 75,000/µL
- •Hgb ≥ 9.0 g/dL
- •Serum Creat. ≤ 1.5xULN or Calc Creat. clearance ≥ 60 mL/min
- •Tot bili ≤ 1.5xULN
- •AST; ALT: ≤ 2.5xULN
排除标准
- •Prostate cancer other than adenocarcinoma, eg. neuroendocrine or small cell histology
- •Concurrent serious medical illness that might interfere with protocol compliance
- •Known chronic infectious disease, eg. AIDS or hepatitis
- •Male patient of reproductive capacity unwilling to use methods appropriate to prevent pregnancy. In the UK, double-barrier contraception required. Patients should continue to use contraception for 3 months after stopping EZN-4176 due to potential for prolonged half-life of EZN-4176 in the liver.
- •History of CNS tumor involvement
- •Other hormonal therapy, eg. megestrol acetate (Megace®), finasteride (Proscar®), dutasteride (Avodart®), or any herbal product known to decrease PSA (e.g., saw palmetto, PC-SPES, and PC-HOPE)
- •> 10 mg/day of prednisone or equivalent systemic corticosteroid within 4 weeks of first dose of EZN-4176
- •Initiation of bisphosphonates within 4 weeks of enrollment. Patients receiving stable doses of bisphosphonates with subsequent tumor progression may continue to receive this medication; however, initiation of bisphosphonates is not allowed during the study.
- •Therapy with supplements or complementary medicines/botanicals within 4 weeks of first dose of study drug, except for any combination of the following: Conventional multivitamin supplements; Selenium; Lycopene; and Soy supplements
- •Prior chemotherapy, immunotherapy, investigational therapeutic agent, or other therapy used to treat the cancer within 4 weeks (6 weeks for prior treatment with mitomycin C or nitrosoureas) before first dose of EZN-4176
- •Radiation or radioactive treatment within 4 weeks before first dose of EZN-
- •Single-fraction palliative radiation is allowed within 2 weeks before first dose of EZN-4176
- •Lack of recovery from any reversible side effects (except alopecia and Grade 1 or 2 neuropathy) to Grade 0 or 1 toxicity related to administration of an investigational therapeutic agent, chemotherapy, immunotherapy, radiotherapy, or other agents previously used to treat the cancer
- •Current participation in another clinical study with an investigational therapeutic agent and/or use of an investigational therapeutic drug (not including investigational use of an approved drug) in the 30 days before first dose of EZN-4176
- •Inability to comply with study protocol
- •Full anticoagulation therapy
研究组 & 干预措施
EZN-4176
Experimental
干预措施: EZN-4176 (Drug)
结局指标
主要结局
Determine the Maximum Tolerated Dose (MTD) of EZN-4176 administered as a weekly 1-hour IV infusion.
时间窗: 2012
Evaluate incidence, severity and duration of adverse events using National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\], Version 4.0, during first cycle.
次要结局
- Determine the recommended Phase 2 dose of EZN-4176(2013)
研究者
研究点 (2)
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