An Open-Label, Parallel, Phase II Study of Single-Agent Oral ESK981 in Men With Castrate-Resistant Prostate Cancer (CRPC)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 2
- 主要终点
- PSA Decline of >= 50% (PSA50) From Baseline
研究概览
简要总结
This phase II trials studies the side effects and how well ESK981 works in treating patients with castration-resistant prostate cancer that has spread to other places in the body. ESK981 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. To determine the PSA >= 50% response rate (PSA50) from baseline using the Prostate Cancer Working Group 3 (PCWG3) criteria to pan-VEGFR/TIE2 tyrosine kinase inhibitor CEP-11981 (ESK981) as a single agent in men with castration-resistant prostate cancer (CRPC) who have progressed on enzalutamide (an oral androgen-receptor inhibitor) and/or abiraterone acetate (an androgen synthesis inhibitor).
II. To assess the safety and tolerability of ESK981 as a single agent.
SECONDARY OBJECTIVES:
I. To determine the time to PSA response to ESK981 in metastatic CRPC patients. II. To determine the duration of PSA response to ESK981 in metastatic CRPC patients.
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 Group (ECOG) performance status =< 1
- •Patient must have evidence of castrate resistant prostate cancer as evidenced by a confirmed rising PSA (per PCWG3 criteria) and a castrate serum testosterone level (i.e. =< 50 mg/dL)
- •Documented histologically confirmed adenocarcinoma of the prostate
- •Metastatic prostate cancer (M1) as documented by appropriate medical imaging (i.e. computed tomography [CT]-scan, positron emission tomography [PET] scan or bone scan)
- •Treatment failure of either abiraterone and/or enzalutamide as evidenced by a confirmed rising PSA (per PCWG3 criteria) and a castrate serum testosterone level (i.e. =< 50 mg/dL) while receiving treatment with either abiraterone and/or enzalutamide
- •Willingness to use contraception by a method that is deemed effective by the Investigator throughout the treatment period and for at least 30 days following the last dose of therapy
- •Willingness and ability to comply with study procedures and follow-up examination
- •Able to swallow and retain oral medication
排除标准
- •Current systemic therapy (other than a gonadotrophin releasing hormone [GnRH] agonist/antagonist) for CRPC including:
- •CYP-17 inhibitors (e.g. ketoconazole, abiraterone)
- •Antiandrogens (e.g. bicalutamide, nilutamide)
- •Second generation antiandrogens (e.g. enzalutamide, ARN-509, Galeterone)
- •Immunotherapy (e.g. sipuleucel-T, ipilimumab)
- •Chemotherapy (e.g. docetaxel, cabazitaxel)
- •Greater than 2 lines of prior systemic therapy for CRPC
- •Prior chemotherapy (e.g. docetaxel, cabazitaxel) for CRPC; prior docetaxel administered in the castrate-sensitive space is allowed
- •Prior radiopharmaceutical therapy (e.g. radium-223, strontium-89, samarium-153, etc.) within the past year
- •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
- •Absolute neutrophil count (ANC) less than 1500/mm^3
- •Platelet count less than 100000/mm^3
- •Hemoglobin less than 9 g/dL
- •Bilirubin greater than 1.5 times the upper limit of normal (ULN)
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2.0 times the ULN in the absence of known hepatic metastases, or ALT or AST greater than 3.0 times the ULN in the presence of known hepatic metastases
- •The patient has a serum creatinine value greater than 1.5 mg/dL
- •The patient has active brain metastases
- •The patient is currently on warfarin or heparin therapy
- •The patient has any pre-existing coagulopathy, recent hemoptysis, gross hematuria, or gastrointestinal bleeding, and a history of a clinically significant cardiovascular or cerebrovascular event within 12 months prior to study entry
- •The patient has uncontrolled hypertension defined as a blood pressure measurement greater than 150 mm Hg systolic or 90 mm Hg diastolic with medication
- •The patient has received any investigational drug within the past 4 weeks
- •The patient has previously been enrolled in the study or received ESK981
- •The patient has known hypersensitivity to gelatin or lactose monohydrate
- •The patient has taken a medication known to be a potent inducer of CYP1A2, CYP2C8, or CYP3A4 within 4 weeks prior to the first dose of study drug
- •The patient has taken a medication known to be a potent inhibitor of CYP1A2, CYP2C8, or CYP3A4 within 2 weeks prior to the first dose of study drug
研究组 & 干预措施
Treatment ESK981
Patients receive pan-VEGFR/TIE2 (Vascular Endothelial Growth Factor Receptor/angopoeitin receptor2) tyrosine kinase inhibitor CEP-11981 PO QD for 5 days (Monday-Friday). Treatment repeats for up to 8 weeks in the absence of disease progression or unacceptable toxicity. If treatment is successful after 8 weeks, patients may receive up to 6 months of pan-VEGFR/TIE2 tyrosine kinase inhibitor CEP-11981.
干预措施: ESK981 (Drug)
结局指标
主要结局
PSA Decline of >= 50% (PSA50) From Baseline
时间窗: Up to 1 year
PSA decline of \>= 50% (PSA50) from baseline using Prostate Cancer Working Group 3 (PCWG3) definition with point estimate and (1-sided Wilson type 90% lower) confidence interval (CI) estimates.
次要结局
- Duration of PSA Response (RD)(From start of PSA50 until PSA progression, assessed up to 1 year)
- PSA Progression Free Survival (PFS)(Date that a 25% or greater increase and an absolute increase of 2.0 ng/mL or more from the nadir is documented and confirmed by a second value obtained 3 or more weeks later, assessed up to 1 year)
- Time to PSA Response(From treatment start until the first documented occurrence of PSA50, assessed up to 1 year)
研究者
Elisabeth Heath
Principal Investigator
Barbara Ann Karmanos Cancer Institute