Phase II Trial of Definitive Radiotherapy With Leuprolide and Enzalutamide in High Risk Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Acute Treatment-related Toxicity
研究概览
简要总结
This phase II trial studies the safety of giving enzalutamide with leuprolide acetate before and after radiation therapy and to see how well it works in treating patients with prostate cancer that is at high risk of returning. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Most types of prostate cancer also need testosterone to grow and spread. After radiation therapy, patients often receive treatments to reduce testosterone to prevent the cancer from returning. Leuprolide acetate works by reducing the amount of testosterone that the body makes. Enzalutamide is a stronger treatment that may block testosterone from reaching cancer cells. Adding enzalutamide to treatment with leuprolide acetate after radiation therapy may help prevent high-risk prostate cancer from returning and improve patient survival.
详细描述
PRIMARY OBJECTIVES:
I. To determine the feasibility and safety of the combination of enzalutamide and leuprolide acetate (leuprolide) in patients undergoing definitive radiation therapy for high-risk prostate cancer or with pelvic nodal involvement.
II. To determine the prostate-specific antigen (PSA) complete response rate with the combination of enzalutamide and leuprolide (PSA-complete response (CR) as determined by PSA nadir =< 0.3) in patients undergoing radiation therapy for high-risk prostate cancer or pelvic nodal involvement.
SECONDARY OBJECTIVES:
I. To determine time to biochemical failure as determined by the American Society for Radiation Oncology (ASTRO) Phoenix definition of nadir + 2 ng/mL, local progression, regional progression, and distant metastases.
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
- •Histologically confirmed diagnosis of adenocarcinoma of the prostate within 180 days prior to registration at very high risk of recurrence as determined by 2 or more of the following combinations:
- •Gleason score 8-10
- •≥33% core involvement OR any patient with pelvic lymph node involvement ≥1cm as determined by pelvic CT or MRI imaging will meet eligibility criteria for enrollment.
- •Standard staging exams for patients with high-risk prostate cancer including bone scan or NaF Positron Emission Tomography (PET) /CT scan, and pelvic and prostate MRI.
- •No distant metastases (M0) on bone scan or NaF PET/CT within 90 days prior to registration. Equivocal bone scan findings are allowed if the physician determines that distant metastases are unlikely based on clinical judgment.
- •Zubrod Performance Status 0-2 within 60 days prior to enrollment.
- •Complete blood count (CBC) with differential obtained within 30 days prior to registration on study, with adequate bone marrow function defined as follows:
- •Absolute neutrophil count (ANC) ≥1,800 cells/mm3
- •Platelets ≥100,000 cells/mm3
- •Hemoglobin ≥8.0 g/dl (The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable)
- •Serum creatinine <2.0 mg/dl and creatinine clearance >40 mL/min within 30 days prior to registration
- •Bilirubin <1.5 x ULN and Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) <2 × ULN within 21 days prior to registration
- •Patients, even if surgically sterilized (i.e., status post vasectomy), who:
- •Agree to practice effective barrier contraception during the entire study treatment period and for 4 months (120 days) after the last dose of study drug, or
- •Agree to completely abstain from intercourse
- •Patient must be able to provide study-specific informed consent prior to study entry.
排除标准
- •Definite evidence of metastatic disease
- •Prior radical prostatectomy or bilateral orchiectomy for any reason
- •Prior invasive malignancy (except non-melanoma skin cancer) unless disease-free or not requiring systemic therapy for a minimum of 3 years.
- •Prior systemic chemotherapy for prostate cancer (Note that prior chemotherapy for a different cancer is allowed).
- •Prior radiotherapy, including brachytherapy, to the region of the prostate that would result in overlap of radiation therapy fields.
- •Previous hormonal therapy such as LHRH agonists (e.g. goserelin, leuprolide), anti-androgens (e.g. flutamide, bicalutamide), estrogens (e.g. DES), or surgical castration (orchiectomy)
- •Known hypersensitivity to enzalutamide or related compounds
- •History of adrenal insufficiency
- •Patients who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
- •Prior allergic reaction to the drugs involved in this protocol.
- •Cushing's syndrome
- •Severe chronic renal disease (serum creatinine >2.0 mg/dl and confirmed by creatinine clearance <40 mL/minute)
- •Chronic liver disease (bilirubin >1.5x ULN, ALT or AST >2x ULN)
- •Active/Uncontrolled Viral Hepatitis
- •Chronic treatment with glucocorticoids within one year.
- •History of seizure including febrile seizure or any condition that may predispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization). Also, current or prior treatment with antiepileptic medications for the treatment of seizures or history of loss of consciousness or transient ischemic attack within 12 months prior to randomization.
- •Clinically significant cardiovascular disease including:
- •Myocardial infarction within 6 months prior to screening
- •Uncontrolled angina within 3 months prior to screening
- •Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multigated acquisition (MUGA) scan performed within 3 months results in a left ventricular ejection fraction that is ≥45%;
- •History of clinically significant ventricular arrhythmias (e.g. ventricular tachycardia, ventricular fibrillation, torsades de pointes);
- •History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place;
- •Uncontrolled hypertension as indicated by a resting systolic blood pressure >170 mm Hg or diastolic blood pressure >105 mm Hg at screening. Patients with initially elevated systolic blood pressure >170 mm Hg or diastolic blood pressure >105 mm Hg are eligible if they undergo medical management and are re-screened.
研究组 & 干预措施
Combination Therapy: Enzalutamide, Leuprolide, Radiotherapy
Participants will receive Enzalutamide: 160 mg per day, to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months as well as a single Leuprolide 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months.
Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.
干预措施: Enzalutamide (Drug)
Combination Therapy: Enzalutamide, Leuprolide, Radiotherapy
Participants will receive Enzalutamide: 160 mg per day, to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months as well as a single Leuprolide 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months.
Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.
干预措施: Leuprolide (Drug)
Combination Therapy: Enzalutamide, Leuprolide, Radiotherapy
Participants will receive Enzalutamide: 160 mg per day, to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months as well as a single Leuprolide 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months.
Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.
干预措施: Intensity-Modulated Radiation Therapy (Radiation)
结局指标
主要结局
Percentage of Participants With Acute Treatment-related Toxicity
时间窗: From start of treatment to 90 days after completion of radiotherapy, approximately 6 months total
Percentage of participants with acute, treatment-related toxicity defined as \<=90 days within the completion of radiotherapy, for any treatment-related grade 3 or higher adverse events as classified by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Proportion of Patients Achieving a Prostate Specific Antigen-Complete Response (PSA-CR)
时间窗: Up to 127 days
A PSA measurement will be obtained at 120-127 days after initiation of androgen deprivation therapy. The proportion of patients achieving a PSA-CR (PSA nadir \<=0.3) at 120-127 days will be determined.
Percentage of Participants With Late Treatment-related Toxicity
时间窗: From 90 days after completion of radiotherapy until end of study, approximately 30 months total
Percentage of participants with late, treatment-related, toxicity is defined as any toxicity occurring \>= 90 days from completion of radiotherapy for any grade 3 or higher treatment-related adverse events as classified by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
次要结局
- Overall Median Change in Fasting Glucose Levels During Treatment(Up to 24 months)
- Overall Median Change in EuroQol Group Five Dimensional Questionnaire (EQ-5D) During Treatment(Up to 24 months)
- Overall Median Change in EuroQol Group Visual Analog Scale (EQ-VAS) During Treatment(Up to 24 months)
- Median Time to Clinical Progression(Up to 36 months)
- Overall Median Change in Hemoglobin A1c (HbA1c) Levels During Treatment(Up to 24 months)
- Median Time to Biochemical Failure(Up to 36 months)
- Overall Median Change in Score on the Expanded Prostate Cancer Index Composite (EPIC) During Treatment(Up to 24 months)
- Overall Median Change in Patient-Reported Outcomes Measurement Information System (PROMIS) - Fatigue Scores During Treatment(Up to 24 months)
- Median Time to Local Failure(Up to 36 months)
- Number of Participants With Regional or Distant Metastases Over Time(Up to 36 months)
- Overall Median Change in Fasting Insulin Levels During Treatment(Up to 24 months)
- Overall Median Change in Lipid Levels During Treatment(Up to 24 months)
- Overall Median Change in Total Cholesterol Levels During Treatment(Up to 24 months)
- Overall Median Change in High-Density Lipoprotein (HDL) Cholesterol Levels During Treatment(Up to 24 months)
- Overall Median Change in Low-Density Lipoprotein (LDL) Cholesterol Levels During Treatment(Up to 24 months)