A Single Arm Study of 6-Months Neoadjuvant Apalutamide Prior to Radical Prostatectomy in Intermediate Risk Patients to Reduce the Frequency of Pathologic Features That Drive Post-Operative Radiation Therapy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Number of Adverse Surgical Pathology Features at Risk of Pelvic Radiation Therapy
研究概览
简要总结
This phase II trial studies how well apalutamide works in treating patients with prostate cancer before radical prostatectomy. Androgen can cause the growth of prostate cancer cells. Hormone therapy using apalutamide may fight prostate cancer by lowering the amount of androgen the body makes and may make it less likely for patients to receive radiation therapy after surgery.
详细描述
PRIMARY OBJECTIVE:
I. To determine whether 6 months (24 weeks) of neoadjuvant apalutamide prior to prostatectomy for intermediate risk prostate cancer results in a reduction of aggregate pathologic risk features that drive post-operative radiotherapy recommendations from 35% to 15%.
SECONDARY OBJECTIVES:
I. To determine the safety and tolerability of 6 months (24 weeks) neoadjuvant apalutamide followed by radical prostatectomy for intermediate risk prostate cancer.
II. To estimate the frequency of clinical complete responses and "near" complete responses (currently defined as < 6 mm total tumor volume).
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
- •Willing and able to provide written informed consent
- •Histologically confirmed adenocarcinoma of the prostate
- •A minimum of 10 core biopsies have been performed at baseline and available. A prostate biopsy within 6 months from screening is allowed for entry requirements. Biopsies performed within 6-12 months from screening are acceptable if the treating physician would allow treatment without further biopsy. Patients must meet intermediate risk criteria from Gleason score, T stage, and prostate-specific antigen (PSA) value by National Comprehensive Cancer Network (NCCN) criteria: cT2b-T2c or Gleason 7 (3+4 or 4+3) or PSA 10-20 ng/mL. In addition, the Gleason 3+4 or 4+3 must be present
- •Pathology review at MD Anderson Cancer Center. The volume of disease must be high enough for the surgeon to agree to include an extended template pelvic lymph node dissection
- •Serum testosterone > 200 ng/mL
- •Patient and urologist must agree that patient is suitable for prostatectomy
- •No evidence of metastases on imaging. This risk group does not require metastatic studies, but if performed they must be negative (as determined by urologist or radiologist). Suspicious lymph nodes permissible if < 10 mm
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Hemoglobin >= 10.0 g/dL
- •Platelet count >= 100,000 x 10^9/microliter
- •Glomerular filtration rate (GFR) >= 45 mL/min
- •Serum potassium >= 3.5 mmol/L
- •Serum albumin >= 3.0 g/dL
- •Able to swallow the study drug whole as a tablet
- •Serum bilirubin < 1.5 x upper limit of normal (ULN); Note: In subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 x ULN, subject may be eligible
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x ULN
- •Normal coagulation profile and no history of substantial non-iatrogenic bleeding diathesis
- •Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug
排除标准
- •Histological variants in the primary tumor, other than adenocarcinoma; for example: neuroendocrine tumor, small cell or sarcomatoid
- •Serious or uncontrolled co-existent non-malignant disease, including active and uncontrolled infection
- •PSA is > than 20 ng/mL (NOTE: unless other valid PSAs were =< 20 and the treating physician considers a value > 20 related to the biopsy or other non-malignant cause. The treating physician must consider the patient intermediate risk in aggregate)
- •Uncontrolled hypertension. Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive therapy. Note that this is NOT a criterion related to particular blood pressure (BP) results at the time of assessment for eligibility, nor does it apply to acute BP excursions that are related to iatrogenic causes, acute pain or other transient, reversible causes
- •Active or symptomatic viral hepatitis or chronic liver disease
- •Clinically significant heart disease as evidenced by myocardial infarction, arterial thrombotic events in the past 6 months, severe or unstable angina, class III-IV New York Heart Association heart failure
- •Other malignancy, except non-melanoma skin cancer, that is active or has a >= 30% probability of recurrence within 12 months
- •History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug
- •Known history of pituitary and/or adrenal disease (or dysfunction)
- •Prior hormone therapy for prostate cancer including orchiectomy, antiandrogens, ketoconazole, or estrogens (5-alpha reductase inhibitors allowed), or luteinizing hormone-releasing hormone (LHRH) agonists/antagonists
- •Severely compromised immunological state, including being positive for the human immunodeficiency virus (HIV)
- •Patients who are not appropriate surgical candidates for radical prostatectomy based on the evaluation of co-existent medical diseases and competing potential causes of death (such as but not limited to, unstable angina, myocardial infarction within the previous 6 months, or use of ongoing maintenance therapy for life-threatening ventricular arrhythmia, uncontrolled hypertension)
- •History of seizure, seizure disorder, or any condition that may predispose to seizure including, but not limited to underlying brain injury, stroke, primary brain tumors, brain metastases, or alcoholism. Also, history of loss of consciousness or transient ischemic attack within 12 months of enrollment (day 1 visit). Drugs may not be used which are known to decrease the seizure threshold
研究组 & 干预措施
Treatment (apalutamide, radical prostatectomy)
Patients receive apalutamide PO daily for 24 weeks in the absence of disease progression or unacceptable toxicity. Within 2 weeks of completing apalutamide, patients undergo radical prostatectomy.
干预措施: Apalutamide (Drug)
Treatment (apalutamide, radical prostatectomy)
Patients receive apalutamide PO daily for 24 weeks in the absence of disease progression or unacceptable toxicity. Within 2 weeks of completing apalutamide, patients undergo radical prostatectomy.
干预措施: Quality-of-Life Assessment (Other)
Treatment (apalutamide, radical prostatectomy)
Patients receive apalutamide PO daily for 24 weeks in the absence of disease progression or unacceptable toxicity. Within 2 weeks of completing apalutamide, patients undergo radical prostatectomy.
干预措施: Radical Prostatectomy (Procedure)
结局指标
主要结局
Number of Adverse Surgical Pathology Features at Risk of Pelvic Radiation Therapy
时间窗: Assessed at time of surgical specimen microscopic evalution Assessed at time of surgical specimen microscopic evaluation
To determine whether 6 months (24 weeks) of neoadjuvant apalutamide prior to prostatectomy for intermediate risk prostate cancer results in a reduction of surgical pathology features at risk of pelvic RT, defined as pT3a, pT3b stage, N1 and/or positive surgical margin. All patients who receive at least 9 weeks of neoadjuvant therapy of apalutamide and undergo radical prostatectomy will be evaluable for the primary endpoint.
次要结局
- Safety and Tolerability of 6 Months Neoadjuvant Apalutamide Followed by Radical Prostatectomy(From initiation of apalutamide through 30 days post-surgery. For those participants who did not have surgery, we assessed the reported AEs until 30 days after the last dose of apalutamide.)
- Clinical Complete Responses (pT0) and "Near" Complete Responses (<6mm Total Tumor Volume)(Assessed at time of surgical specimen microscopic evaluation)
- Biochemical Recurrence Rate(From surgery through 3-year post-op follow up)