Establishing a Neo-Adjuvant Platform for Developing Targeted Agents: Androgen Deprivation Therapy Prior to Prostatectomy for Patients With Intermediate and High Risk Prostate Cancer
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- To assess between the time to determine the time of the maximal change in prostate cancer cell proliferation (Ki-67) and apoptosis rates (cleaved caspase-3)
研究概览
简要总结
Degarelix is an approved drug that is used to treat prostate cancer by lowering testosterone levels in the body.
Degarelix is commonly given with radiation for prostate cancer, but less frequently with surgery since there has been no proven benefit with this approach.
The investigators do not expect the patient to benefit directly from treatment with degarelix since their prostate will be removed shortly after the drug is given. Instead, the investigators hope to learn about how degarelix and other treatment that lowers your testosterone effects prostate cancer cells and use this information to develop better treatments in the future.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Histologic confirmation of prostatic adenocarcinoma by MSKCC inclusive of the following:
- •3 or more positive biopsy cores or equivalent tumor specimen as confirmed by pathologist
- •At least 2 cores containing ≥3 mm of tissue with carcinoma or equivalent tumor specimen as confirmed by pathologist
- •A primary tumor Gleason score ≥ 7
- •Adequate primary biopsy tissue or equivalent tumor specimen as confirmed by pathologist available for protocol required analysis (i.e. bladder or TURP specimen)
- •Planning to have or have had a radical prostatectomy (RP) at MSKCC
- •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 RP
- •Karnofsky performance status >70% (Appendix A)
- •Sexually active fertile subjects, and their partners, must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 3 months after the dose of study drug(s) for Cohorts 1 , 2 and 4, and for 3 months after the surgery for Cohort 3
- •For cohorts 1,2 and 4 only:, non-castrate testosterone level (>100 ng/dL)
- •For cohort 3 only:, 1-6 months of androgen deprivation therapy (gonadotropin hormone releasing analogs with or without an anti-androgen) prior to prostatectomy with a castrate testosterone level of <50 ng/dL within 1 month prior to prostatectomy.
排除标准
- •Histologic variants in the primary tumor (histologic variants other than adenocarcinoma)
- •Current or prior chemotherapy
- •The use of the 5-alpha-reductase inhibitor dutasteride must be discontinued within 4 weeks of degarelix injection for Cohort 1, 2 and 4, and within 4 weeks of surgery for Cohort
- •Saw palmetto administered with the intent to treat the patient's malignancy within 1 week of degarelix injection for Cohorts 1, 2 and 4, and for within 1 week of surgery for Cohort 3
- •Current or prior radiation therapy to the prostate
- •Active infection or intercurrent illness
- •Concomitant therapy with any other experimental drug
- •For cohorts 1, 2 and 4 only:, current or prior hormonal therapy (e.g., gonadotropin hormone releasing analogs, megestrol acetate, or antiandrogens) are exclusionary
研究组 & 干预措施
treated patients with androgen deprivation
Patients already treated with androgen deprivation are assigned to Cohort 3 and maintained on current androgen deprivation therapy until they undergo or have already undergone RP at MSKCC. Will include patients who have already undergone hormonal therapy (of any duration between 1 and 6 months) prior to prostatectomy.
干预措施: androgen deprivation therapy (Drug)
Untreated patients degarelix injection occur at days 14±1
Treatment will consist of a single 240 mg injection of degarelix 14±1 day before radical prostatectomy
干预措施: degarelix injection (Drug)
Untreated patients degarelix injection occur at days 4± 1
Treatment will consist of a single 240 mg injection of degarelix 4 ± 1 day before radical prostatectomy
干预措施: degarelix injection (Drug)
Untreated patients degarelix injection occur at days and 7± 1.
Treatment will consist of a single 240 mg injection of degarelix 7±1 day before radical prostatectomy
干预措施: degarelix injection (Drug)
结局指标
主要结局
To assess between the time to determine the time of the maximal change in prostate cancer cell proliferation (Ki-67) and apoptosis rates (cleaved caspase-3)
时间窗: 2 years
The primary endpoint is the change in the rate of proliferation (Ki-67) and the rate of apoptosis (cleaved caspase-3), as evaluated by IHC in anatomically matched tumor foci from the pre-treatment diagnostic biopsy and the RP specimen. The levels in pre-treatment biopsy serve as the baseline. Ki-67 is a widely accepted nuclear marker for cell proliferation. Cleaved caspase-3 has been shown to be a reliable marker of apoptosis and correlate with results from other apoptosis markers such as cleaved PARP-1 and TUNEL assay.
Percent Change in Prostate Cancer Cell Proliferation (Ki-67 Levels)
时间窗: Baseline and up to 2 years
The primary endpoint is the change in the rate of proliferation (Ki-67), as evaluated by IHC in anatomically matched tumor foci from the pre-treatment diagnostic biopsy and the RP specimen. The levels in pre-treatment biopsy serve as the baseline. Ki-67 is a widely accepted nuclear marker for cell proliferation.
次要结局
- To explore the association between PTEN status and maximal changes in prostate cancer proliferation and apoptosis rates in patients treated with androgen deprivation therapy(2 years)
- To explore the association between PI3K pathway (pAKT and pS6) and prostate cancer proliferation and apoptosis rates after treatment with androgen deprivation therapy in relation to other markers of prostate cancer (ERG, AR and NCOA2).(2 years)
- To discover novel biomarkers and correlates of response(2 years)
- Median Percentage of Cells From Biopsy and Surgery That Are Positive For Ki-67(up to 2 years)
- Record Participant Biomarker Results and Correlates of Response(Up to 14+/- days)