Neoadjuvant Androgen Depletion in Combination With Vorinostat Followed by Radical Prostatectomy for Localized Prostate Cancer: Total Androgen-Receptor Gene Expression Targeted Therapy (TARGET)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 15
- 主要终点
- Pathologic Complete Response at the Time of Surgery
研究概览
简要总结
This phase II trial studies how well androgen deprivation therapy and vorinostat followed by radical prostatectomy works in treating patients with prostate cancer that has not spread to other parts of the body. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide, goserelin acetate, and leuprolide acetate, may lessen the amount of androgens made by the body. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving androgen deprivation therapy and vorinostat before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
详细描述
PRIMARY OBJECTIVES:
I. To determine the rate of pathologic complete response in patients with localized prostate cancer treated with androgen depletion therapy (ADT) and oral vorinostat administered for a minimum of 6 weeks and maximum of 8 weeks before radical prostatectomy.
SECONDARY OBJECTIVES:
I. To determine and evaluate pre- and post-treatment levels of prostate-specific antigen (PSA), testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone-dulfate (DHEA-S) in blood.
II. To determine and evaluate pre- and post-treatment levels of testosterone, androstenedione, androstenediol, DHT, DHEA, and DHEA-S in prostate.
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
- 19 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologic documentation of prostatic adenocarcinoma in 3 or more biopsy cores, of which at least 1 core demonstrates > 30% involvement with tumor; confirmation of localized disease by magnetic resonance imaging (MRI) with endorectal probe if available
- •No evidence of distant disease on a:
- •Computed tomography (CT) or MRI of the abdomen and pelvis
- •Radionuclide bone scan (with plain film or MRI confirmation as clinically indicated)
- •Appropriate candidate for radical prostatectomy
- •Adequate cardiac function (evidence of cardiac disease should be evaluated to determine appropriateness of patient as a surgical candidate)
- •Candidates may have a history of deep vein thrombosis, pulmonary embolism, and/or cerebrovascular accident, or require concomitant systemic anticoagulation, if otherwise deemed to be suitable for radical prostatectomy
- •White blood cell (WBC) > 3000/uL
- •Platelets > 150,000/uL
- •Creatinine < 2 mg/dL
- •Serum PSA < 100 ng/mL
- •Bilirubin < 1.5 X ULN (institutional upper limits of normal)
- •Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2 X ULN
- •Karnofsky performance status > 70%
- •Willingness to undergo pretreatment transrectal ultrasound-guided prostate needle biopsy (optional)
- •Willingness to use adequate contraceptive methods during study therapy and for at least 3 months after completion of therapy
- •Ability to understand and willingness to sign a written informed consent document
排除标准
- •Evidence of small-cell, transitional-cell, or neuroendocrine pathologic features
- •Prior hormonal therapy with (e.g. 5-alpha-reductase inhibitors, gonadotropin hormone releasing analogs, steroids, megestrol acetate, or nonstudy-related antiandrogens), chemotherapy, or herbal medications administered with the intent to treat the patient's malignancy
- •Patients on valproic acid (a histone-deacetylase inhibitor) to treat prostate cancer are not eligible
- •History of allergic reactions attributed to compounds of similar chemical or biological composition to vorinostat
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would compromise compliance with study requirements
- •Currently active secondary malignancy (as determined by the treating physician) other than non-melanoma skin cancer
研究组 & 干预措施
Treatment (Antihormone therapy and enzyme inhibitor therapy)
Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician.
干预措施: Bicalutamide (Drug)
Treatment (Antihormone therapy and enzyme inhibitor therapy)
Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician.
干预措施: Goserelin Acetate (Drug)
Treatment (Antihormone therapy and enzyme inhibitor therapy)
Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (Antihormone therapy and enzyme inhibitor therapy)
Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician.
干预措施: Leuprolide Acetate (Drug)
Treatment (Antihormone therapy and enzyme inhibitor therapy)
Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician.
干预措施: Therapeutic Conventional Surgery (Procedure)
Treatment (Antihormone therapy and enzyme inhibitor therapy)
Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician.
干预措施: Vorinostat (Drug)
结局指标
主要结局
Pathologic Complete Response at the Time of Surgery
时间窗: At 12 weeks
The primary endpoint will be pathologic complete response at the time of surgery. This represents the proportion of patients with no evidence of disease in the prostate (ie, the absence of tumor in the posttherapy pathology specimen) at the time of radical prostatectomy. Pathologic complete response at the time of surgery is the primary endpoint for this study. A Simon 2-stage optimal design that differentiates between response probabilities of 0.05 and 0.20 will be used in the analysis of the pathological complete response at 12 weeks (Type I error 10% and power 90%). A maximum of 38 pts were planned for accrual onto this study. If zero or one response was observed, then the trial was to be stopped. The design had power 0.90 for a population response proportion to 0.20 using a one-sided 0.10 size test. pT2 indicates that the cancer is confined to the prostate, while pT3 indicates that there is an extraprostatic extension of the cancer.
次要结局
- Gleason Score(Baseline)
- Levels of DHEA in Blood From Radical Prostatectomy Specimens(Up to 1 year)
- Levels of DHEA-S in Blood From Radical Prostatectomy Specimens(Up to 1 year)
- Levels of DHT in Blood From Radical Prostatectomy Specimens(Up to 1 year)
- Levels of PSA in Blood From Radical Prostatectomy Specimens(Up to 1 year)
- Levels of Testosterone in Blood From Radical Prostatectomy Specimens(Up to 1 year)