Phase Ib Trial of Enzalutamide in Combination With Radiation Therapy and LHRH Agonist Therapy in the Management of Intermediate and High-Risk Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Acute toxicities, monitored using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 criteria
研究概览
简要总结
This phase I trial studies the side effects and best way to give enzalutamide, radiation therapy, and hormone therapy in treating patients with intermediate or high-risk prostate cancer. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as enzalutamide, may lessen the amount of androgens made by the body. Radiation therapy uses high energy x rays to kill tumor cells. Giving enzalutamide, radiation therapy, and hormone therapy may be an effective treatment for prostate cancer.
详细描述
PRIMARY OBJECTIVE:
1) To assess the safety of the combination of neoadjuvant and concurrent enzalutamide with an luteinizing-hormone-releasing hormone (LHRH) agonist and radiation therapy.
SECONDARY OBJECTIVES:
- To determine the efficacy of the combination of enzalutamide with an LHRH agonist and radiation therapy using prostate specific antigen (PSA) kinetics.
- To determine the efficacy of the combination of enzalutamide with an LHRH agonist and radiation therapy using PSA nadir.
- To describe patient-reported outcomes including: Expanded Prostate Cancer Index Composite (EPIC), American Urological Association (AUA) Symptom Index, PROstate magnetic resonance (MR) Imaging Study (PROMIS) Fatigue Scale.
OUTLINE:
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
- •Prostate adenocarcinoma without distant metastatic disease with either Gleason score ≥ 7, PSA ≥ 10 ng/ml, or T2b or greater disease
- •Performance Status: ECOG 0-1
- •Hematologic (minimal values):
- •Absolute neutrophil count > 1,500/mm3
- •Hemoglobin > 8.0 g/dl
- •Platelet count > 100,000/mm3
- •Hepatic function
- •Total bilirubin < Upper limit of normal (ULN)(except for Gilbert's disease)
- •AST (SGOT) < 1.5 x ULN
- •ALT (SGPT) < 1.5 x ULN
- •Creatinine < 1.5 x ULN
- •Men of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.
排除标准
- •Patients with a history of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, brain arteriovenous malformation or the use of concomitant medications that may lower the seizure threshold
- •History of urological surgery or procedures predisposing to GU complications after radiation (will be determined by radiation oncologist)
- •History of diverticulitis, rectal bleeding or other lower GI diseases predisposing to GI complications after radiation (will be determined by radiation oncologist)
- •History of prior chemotherapy or pelvic irradiation,
- •History of prior invasive malignant cancer(s) within the last 5 years except adequately treated or controlled basal cell or squamous cell carcinoma of the skin.
- •Documented distant metastatic disease. NOTE: pelvic lymphadenopathy is NOT excluded.
- •Prior radical prostatectomy or cryosurgery for prostate cancer or bilateral orchiectomy.
- •No experimental medications within 30 days of study entry
- •Patients currently taking the following medications:
- •CYP2C8 inhibitors (e.g. Gemfibrozil)
- •CYP2C8 inducers (e.g. rifampin)
- •CYP3A4 inhibitors (itraconazole)
- •CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine)
研究组 & 干预措施
Treatment (enzalutamide, radiation therapy, hormone therapy)
Patients receive enzalutamide PO QD for 6 months. Beginning 2 weeks after start of enzalutamide, patients receive LHRH agonist therapy with goserelin acetate SC or leuprolide acetate IM or SC for 6 months (intermediate risk patients) or 24 months (high risk patients) post-radiation therapy. Beginning 8 weeks after the start of LHRH therapy, patients undergo either IMRT or VMAT daily five days a week for 8 weeks.
干预措施: Enzalutamide (Drug)
Treatment (enzalutamide, radiation therapy, hormone therapy)
Patients receive enzalutamide PO QD for 6 months. Beginning 2 weeks after start of enzalutamide, patients receive LHRH agonist therapy with goserelin acetate SC or leuprolide acetate IM or SC for 6 months (intermediate risk patients) or 24 months (high risk patients) post-radiation therapy. Beginning 8 weeks after the start of LHRH therapy, patients undergo either IMRT or VMAT daily five days a week for 8 weeks.
干预措施: Goserelin acetate (Drug)
Treatment (enzalutamide, radiation therapy, hormone therapy)
Patients receive enzalutamide PO QD for 6 months. Beginning 2 weeks after start of enzalutamide, patients receive LHRH agonist therapy with goserelin acetate SC or leuprolide acetate IM or SC for 6 months (intermediate risk patients) or 24 months (high risk patients) post-radiation therapy. Beginning 8 weeks after the start of LHRH therapy, patients undergo either IMRT or VMAT daily five days a week for 8 weeks.
干预措施: Leuprolide acetate (Drug)
Treatment (enzalutamide, radiation therapy, hormone therapy)
Patients receive enzalutamide PO QD for 6 months. Beginning 2 weeks after start of enzalutamide, patients receive LHRH agonist therapy with goserelin acetate SC or leuprolide acetate IM or SC for 6 months (intermediate risk patients) or 24 months (high risk patients) post-radiation therapy. Beginning 8 weeks after the start of LHRH therapy, patients undergo either IMRT or VMAT daily five days a week for 8 weeks.
干预措施: Radiation therapy (Radiation)
结局指标
主要结局
Acute toxicities, monitored using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 criteria
时间窗: Up to 1 month post completion of enzalutamide
An exact 2-sided binomial 90% confidence interval will be computed and reported. Toxicity will be monitored and if there is greater than 10% incidence of grade 3 or higher gastrointestinal (GI)/genitourinary (GU)/fatigue lasting more than 7 days despite optimal treatment, the trial will be re-evaluated.
次要结局
- Change in PSA levels(Baseline up to 6 months)
- Quality of life (QoL), measured using the EPIC, AUA symptom index, and the PROMIS Fatigue Scale(Baseline up to 1 year)