A Phase I Study of Niclosamide in Combination With Enzalutamide in Men With Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Recommended phase 2 dose
研究概览
简要总结
This phase I trial studies the side effects and best dose of niclosamide when given together with enzalutamide in treating patients with castration resistant prostate cancer that has spread from the primary site to other places in the body. Androgens such as testosterone can cause the growth of prostate cancer cells. Drugs like enzalutamide block androgens from driving tumor growth; however, when androgen receptor splice variants are present, these drugs may not be effective. Niclosamide may decrease the amount of androgen receptor splice variant present within tumor cells, thus promoting the anti-tumor effects of enzalutamide. Giving niclosamide together with enzalutamide may be a better treatment for prostate cancer.
详细描述
PRIMARY OBJECTIVES:
I. Determine the safety and tolerability of three-times-daily (TID) oral niclosamide combined with enzalutamide in men with castration-resistant prostate cancer (CRPC) that has progressed on abiraterone (abiraterone acetate).
SECONDARY OBJECTIVES:
I. Determine the effect of niclosamide plus enzalutamide on androgen receptor splice variant (AR-V) expression as determined by quantitative reverse-transcriptase-polymerase-chain-reaction (qRT-PCR).
II. Determine the pharmacokinetic profile of three-times-daily (TID) oral niclosamide in men with castration-resistant prostate cancer (CRPC) that has progressed on abiraterone.
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
- •Have signed an informed consent document indicating that the subject understands the purpose of and procedures required for the study and are willing to participate in the study
- •Be willing/able to adhere to the prohibitions and restrictions specified in this protocol
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- •Documented histologically confirmed adenocarcinoma of the prostate
- •Patient must have evidence of castration resistant prostate cancer as evidenced by a confirmed rising PSA (per Prostate Cancer Working Group 2 [PCWG2] criteria) and a castrate serum testosterone level (i.e. =< 50 mg/dL)
- •Patient must be eligible for treatment with enzalutamide
- •Patient must have previously progressed on abiraterone (either by PCWG2 criteria or Response Evaluation Criteria in Solid Tumors [RECIST] criteria)
- •Documented metastatic disease on bone scan, computed tomography (CT) scan or magnetic resonance imaging (MRI)
排除标准
- •Have known allergies, hypersensitivity, or intolerance to enzalutamide or niclosamide or their excipients
- •Ongoing systemic therapy (other than a gonadotropin releasing hormone [GnRH] agonist/antagonist) for prostate cancer including, but not limited to:
- •Cytochrome P450, family 17 (CYP-17) inhibitors (e.g. ketoconazole, abiraterone)
- •Antiandrogens (e.g. bicalutamide, nilutamide)
- •Second generation antiandrogens (e.g. ARN-509)
- •Note: patients receiving ongoing treatment with enzalutamide will be allowed to join the study
- •Immunotherapy (e.g. sipuleucel-T, ipilimumab)
- •Chemotherapy (e.g. docetaxel, cabazitaxel)
- •Radiopharmaceutical therapy (e.g. radium-223, strontium-89, samarium-153)
- •Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements
- •Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule
- •Severe hepatic impairment (Child-Pugh class C)
- •Severe renal impairment (creatinine clearance =< 30 ml/min)
- •History of prior seizures
- •Central nervous system metastases
- •Symptomatic patients who, in the opinion of the investigator, may benefit from docetaxel-based chemotherapy
研究组 & 干预措施
Treatment (niclosamide, enzalutamide)
Patients receive niclosamide PO TID and enzalutamide PO daily. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Enzalutamide (Drug)
Treatment (niclosamide, enzalutamide)
Patients receive niclosamide PO TID and enzalutamide PO daily. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (niclosamide, enzalutamide)
Patients receive niclosamide PO TID and enzalutamide PO daily. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Niclosamide (Drug)
Treatment (niclosamide, enzalutamide)
Patients receive niclosamide PO TID and enzalutamide PO daily. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
结局指标
主要结局
Recommended phase 2 dose
时间窗: Up to 28 days
Incidence of dose-limiting toxicities, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
时间窗: Up to 28 days
次要结局
- Half-life of niclosamide(0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours and 15 days after the first dose of niclosamide)
- Maximum concentration of niclosamide(0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours and 15 days after the first dose of niclosamide)
- Minimum concentration of niclosamide(0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours and 15 days after the first dose of niclosamide)
- Steady state concentration of niclosamide(0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours and 15 days after the first dose of niclosamide)
- PSA response rate(Baseline to up to 28 days)