A Phase II Neoadjuvant Study of Apalutamide, Abiraterone Acetate, Prednisone, Degarelix and Indomethacin in Men With Localized Prostate Cancer Pre-Prostatectomy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Pathologic Complete Response Rate as Assessed From Prostatectomy Specimens Following Neoadjuvant Treatment
研究概览
简要总结
This phase II trial studies how well apalutamide, abiraterone acetate, prednisone, degarelix, and indomethacin work in treating patients with prostate cancer that has spread from where it started to nearby tissue or lymph nodes before surgery. Androgen can cause the growth of tumor cells. Hormone therapy using apalutamide, abiraterone acetate, prednisone, degarelix, and indomethacin may fight prostate cancer by lowering the amount of androgen the body makes and/or blocking the use of androgen by the tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. The rate of the pathologic complete response (pCR) (i.e. no evidence of residual tumor) as assessed on prostatectomy specimens following 3-months (12 weeks) of neoadjuvant apalutamide, abiraterone acetate, degarelix and indomethacin.
SECONDARY OBJECTIVES:
I. To determine the negative margin rate as assessed on prostatectomy specimens following 3-months (12 weeks) of neoadjuvant apalutamide, abiraterone acetate, degarelix and indomethacin.
II. To determine the rate of near pCR (i.e. =< 5 mm of residual tumor) as assessed on prostatectomy specimens following 3-months (12 weeks) of neoadjuvant apalutamide, abiraterone acetate, degarelix and indomethacin.
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
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- •Documented histologically confirmed adenocarcinoma of the prostate
- •Willing to undergo prostatectomy as primary treatment for localized prostate cancer
- •High risk prostate cancer (per National Comprehensive Cancer Network [NCCN] criteria): Gleason score 8-10 or T3a or PSA > 20 ng/mL or very-high risk prostate cancer (per NCCN criteria): T3b-T4
- •Serum testosterone >= 150 ng/dL
- •Able to swallow the study drugs whole
- •Willing to take abiraterone acetate on an empty stomach (no food should be consumed at least two hours before and for one hour after dosing)
- •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
- •Medications known to lower the seizure threshold (see list under prohibited meds) must be discontinued or substituted at least 4 weeks prior to study entry
排除标准
- •Prior local therapy to treat prostate cancer (e.g. radical prostatectomy, radiation therapy, brachytherapy)
- •Prior use of apalutamide, abiraterone acetate or degarelix
- •Prior or ongoing systemic therapy for prostate cancer including, but not limited to:
- •Hormonal therapy (for example [e.g.] leuprolide, goserelin, triptorelin, degarelix)
- •Cytochrome P450 (CYP)-17 inhibitors (e.g. ketoconazole)
- •Antiandrogens (e.g. bicalutamide, nilutamide)
- •Second generation antiandrogens (e.g. enzalutamide, apalutamide)
- •Immunotherapy (e.g. sipuleucel-T, ipilimumab)
- •Chemotherapy (e.g. docetaxel, cabazitaxel)
- •Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study
- •Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule
- •Absolute neutrophil count [ANC] < 1500/mm^3
- •Platelet count < 100,000/mm^3
- •Hemoglobin < 9 g/dL
- •Total bilirubin > 1.5 x upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >= 2.5 x 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
- •Abnormal kidney function (glomerular filtration rate GFR < 45 mL/min)
- •Serum albumin < 3 g/dL
- •Serum potassium < 3.5 mmol/L
- •Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year to randomization, brain arteriovenous malformation, schwannoma, meningioma, or other benign central nervous system [CNS] or meningeal disease which may require treatment with surgery or radiation therapy)
- •Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to randomization
- •History of stroke within the last 5-years
- •History of gastrointestinal (GI) bleed requiring transfusion
- •History of peptic ulcer disease requiring treatment within the last 5-years
- •History of asthma that is nonsteroidal anti-inflammatory drug (NSAID)-induced or with asthma that is classified as 'mild-persistent' or worse (based on symptoms occurring more than 2 days per week)
- •Uncontrolled hypertension
- •Gastrointestinal disorder affecting absorption
- •Active infection (eg, human immunodeficiency virus [HIV] or viral hepatitis)
- •Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/ prednisolone once daily
- •Any condition that in the opinion of the investigator, would preclude participation in this study
- •Child Pugh class B & C
- •Pre-existing viral hepatitis
研究组 & 干预措施
Treatment (neoadjuvant chemotherapy)
Patients receive androgen receptor antagonist ARN-509 and abiraterone acetate PO daily, prednisone PO BID and indomethacin PO TID. Patients also receive degarelix SC on day 1 and every 4 weeks for 3 doses. Treatment continues for up to 12 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo prostatectomy on day 85.
干预措施: Abiraterone Acetate (Drug)
Treatment (neoadjuvant chemotherapy)
Patients receive androgen receptor antagonist ARN-509 and abiraterone acetate PO daily, prednisone PO BID and indomethacin PO TID. Patients also receive degarelix SC on day 1 and every 4 weeks for 3 doses. Treatment continues for up to 12 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo prostatectomy on day 85.
干预措施: Apalutamide (Drug)
Treatment (neoadjuvant chemotherapy)
Patients receive androgen receptor antagonist ARN-509 and abiraterone acetate PO daily, prednisone PO BID and indomethacin PO TID. Patients also receive degarelix SC on day 1 and every 4 weeks for 3 doses. Treatment continues for up to 12 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo prostatectomy on day 85.
干预措施: Degarelix (Drug)
Treatment (neoadjuvant chemotherapy)
Patients receive androgen receptor antagonist ARN-509 and abiraterone acetate PO daily, prednisone PO BID and indomethacin PO TID. Patients also receive degarelix SC on day 1 and every 4 weeks for 3 doses. Treatment continues for up to 12 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo prostatectomy on day 85.
干预措施: Indomethacin (Drug)
Treatment (neoadjuvant chemotherapy)
Patients receive androgen receptor antagonist ARN-509 and abiraterone acetate PO daily, prednisone PO BID and indomethacin PO TID. Patients also receive degarelix SC on day 1 and every 4 weeks for 3 doses. Treatment continues for up to 12 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo prostatectomy on day 85.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (neoadjuvant chemotherapy)
Patients receive androgen receptor antagonist ARN-509 and abiraterone acetate PO daily, prednisone PO BID and indomethacin PO TID. Patients also receive degarelix SC on day 1 and every 4 weeks for 3 doses. Treatment continues for up to 12 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo prostatectomy on day 85.
干预措施: Prednisone (Drug)
结局指标
主要结局
Pathologic Complete Response Rate as Assessed From Prostatectomy Specimens Following Neoadjuvant Treatment
时间窗: At 3 months
Pathologic complete response is defined as no evidence of cancer on fully submitted prostatectomy specimens using standard surgical pathology assessments (i.e. H\&E assessment will be used for the purpose of defining pathologic complete response per protocol) at 3 months.
次要结局
- Number of Participants Without Biochemical Failure at 2 Years(At 2 years)
- The Proportion of Men Who Receive Adjuvant Radiation Therapy(Up to 1 year post prostatectomy)
- Number of Patients With a Negative Margin After 3 Months of Treatment(At 3 months)
- Number of Patients With a Near Pathologic Complete Response After 3 Months of Treatment(At 3 months)
- Number of Patients With Pathologic T3 Disease After 3 Months of Treatment.(At 3 months)
- Overall Survival (OS)(At 2 years)
- Apoptotic Index (i.e. Percentage of Tumor Cells Undergoing Apoptosis)(At 3 months)
- Number of Patients With no Nodal Metastases After 3 Months of Treatment.(At 3 months)
研究者
Michael Schweizer
Associate Professor, Division of Medical Oncology
University of Washington