Prostate Androgen Response Investigation Using a Stratification BIOmarker; Predicting Prostate Cancer Downstaging by Neoadjuvant Darolutamide With PCAI ImmunoScore (PARIS-BIO)
PARIS-BIO - Prostate Androgen Response Investigation Using a Stratification BIOmarker; Predicting Prostate Cancer Downstaging by Neoadjuvant Darolutamide With PCAI ImmunoScore in a Non-randomised Open Label Prospective Trial
研究概览
详细说明
High-risk prostate cancer patients are at risk for recurrence after local therapy. The presence of micro-metastatic disease, undetectable by conventional imaging, likely contributes to the poor prognosis. Neoadjuvant hormonal therapy, particularly with the advent of ARPIs like Darolutamide, has shown promise, but patient selection remains crucial for optimizing outcomes. This Phase II, single-arm, open-label trial investigates the predictive value of the PCAI ImmunoScore, a gene expression signature derived from diagnostic biopsies.
100 participants with high-risk prostate cancer scheduled for radical prostatectomy will be enrolled. They will receive Darolutamide (600 mg twice daily) for a period of 90 to 120 days. MRI imaging will be performed between day 90 and 120 prior to surgery. Radical prostatectomy is performed within the same window.
The primary analysis compares the pre-treatment biomarker score with the pathological response (Minimal Residual Disease) observed in the surgical specimen. Secondary analyses include MRI response, PSA kinetics, and patient-reported functional outcomes.
研究类型
注册 (估计的)
阶段
- 阶段2
联系人和位置
学习联系方式
- 姓名：Per H Vincent, MScEng, PhD
- 电话号码：+46(0)708239320
- 邮箱：per.vincent@regionstockholm.se
研究联系人备份
- 姓名：Sara Göransson, PhD
- 电话号码：+46(0)812377000
- 邮箱：sara.goransson@regionstockholm.se
学习地点
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Gothenburg、瑞典
- 招聘中
- Sahlgrenska University Hospital
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接触：
- Johan Stranne, MD, Professor
- 电话号码：+46(0)709558865
- 邮箱：johan.stranne@vgregion.se
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首席研究员：
- Johan Stranne, MD, Professor
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Stockholm、瑞典、SE-17176
- 招聘中
- Karolinska University Hospital
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接触：
- Johan Björklund, MD, PhD
- 电话号码：+46(0)709583113
- 邮箱：johan.bjorklund@regionstockholm.se
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接触：
- Axel Möller, MD, PhD
- 电话号码：+46(0)706271734
- 邮箱：axel.moller@regionstockholm.se
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首席研究员：
- Johan Björklund, MD, PhD
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参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
Inclusion Criteria:
- Biopsy-confirmed high-risk prostate cancer defined as: Global ISUP score > 3 with any MRI PI-RADS score OR Global ISUP score = 3 with MRI PI-RADS score = 5
- Candidate for radical prostatectomy
- Clinical prostate MRI not older than 3 months at screening
- ECOG performance status score of 0 or 1
- Able to receive Darolutamide for 90-120 days
- Signed informed consent form
- Willingness to use contraception if sexually active
Exclusion Criteria:
- Metastatic (M1) or node-positive (N2) disease
- Prior treatment with androgen receptor antagonists
- Prior treatment with gonadotropin-releasing hormone (GnRH)
- History of prior systemic or local therapy for prostate cancer (including radiation and focal therapy)
- Major surgery <4 weeks prior to inclusion
学习计划
研究是如何设计的？
设计细节
- 主要用途：其他
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：Neoadjuvant Darolutamide
All participants receive Darolutamide 600 mg orally twice daily for 90-120 days prior to radical prostatectomy
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Neoadjuvant Darolutamide alone (without ADT) 2x300 mg orally twice daily is given to all study subjects for 90-120 days prior to prostatectomy.
其他名称：
Robot-assisted radical prostatectomy, with or without extirpation of pelvic lymph nodes according to clinician's choice in concordance with local guidelines
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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The association between the pre-treatment probability of treatment response given by PCAI ImmunoScore and the occurrence of minimal residual disease (MRD)
大体时间：MRD is ascertained shortly after radical prostatectomy (day 90-120). PCAI ImmunoScore will be ascertained after bulk sequencing of all samples, tentatively 1 year after surgery of the 100th study subject. The association will be calculated thereafter.
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The primary outcome is the association between the pre-treatment PCAI ImmunoScore and the occurrence of minimal residual disease (MRD) after 90-120 days of neoadjuvant Darolutamide treatment.
MRD is defined as < 0.05 cm3 residual tumour on final pathology after prostatectomy.
The study endpoint MRD will be dichotomized into responder (if MRD is met) or non-responder (if MRD is not met) as input for the statistical data analysis.
This classification (ground truth) will be tested in AUROC analysis against the calculated PCAI ImmunoScore-based probability p (0<p<1) of Darolutamide response.
PCAI ImmunScore is calculated from RNA sequencing of tumor material from diagnostic (pre-treatment) biopsies.
The collection of RNA and calculation of PCAI ImmunoScore will take place after the recruitment period.
Sequencing will be performed in bulk once all samples have been collected.
The objective is to assess the predictive value of the pre-treatment genomic biomarker for pathological response.
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MRD is ascertained shortly after radical prostatectomy (day 90-120). PCAI ImmunoScore will be ascertained after bulk sequencing of all samples, tentatively 1 year after surgery of the 100th study subject. The association will be calculated thereafter.
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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The association between PCAI ImmunoScore and pathologic complete response (pCR)
大体时间：pCR is ascertained shortly after radical prostatectomy (day 90-120). PCAI ImmunoScore will be ascertained after bulk sequencing of all samples, tentatively 1 year after surgery of the 100th study subject. The association will be calculated thereafter.
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The study endpoint pCR is defined as no residual tumour visible at final pathology and will be dichotomized into responder (if pCR is met) or non-responder (if pCR is not met) as input for the statistical data analysis.
This classification (ground truth) will be tested in AUROC analysis against the calculated PCAI ImmunoScore-based probability p (0<p<1) (baseline model) of Darolutamide response.
The extended model including the additional covariates will be tested equivalent to the baseline model.
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pCR is ascertained shortly after radical prostatectomy (day 90-120). PCAI ImmunoScore will be ascertained after bulk sequencing of all samples, tentatively 1 year after surgery of the 100th study subject. The association will be calculated thereafter.
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Pathological T-stage (pT-stage)
大体时间：Pathological T-stage will be ascertained shortly after radical prostatectomy (day 90-120)
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Staging of the tumor at final pathology
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Pathological T-stage will be ascertained shortly after radical prostatectomy (day 90-120)
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Residual tumor size
大体时间：At the time of radical prostatectomy (day 90-120)
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Measurement of the largest cross-sectional dimensions (mm) of residual tumor
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At the time of radical prostatectomy (day 90-120)
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PSA Kinetics
大体时间：Baseline, Day 30, Day 60, Day 90, and within 4 weeks after surgery
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Change in blood PSA concentration (ng/ml) during treatment
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Baseline, Day 30, Day 60, Day 90, and within 4 weeks after surgery
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Hormonal side effects
大体时间：From baseline up to 12 months post-surgery
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Incidence and severity of adverse events assessed by CTCAE v5.0 and patient-reported quality-of-life using the 26-question questionnaire Expanded Prostate cancer Index Composite (EPIC-26), where lower scores indicate worse outcome
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From baseline up to 12 months post-surgery
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Patient-reported urinary continence
大体时间：Pre-surgery (day 80-119), 3 months post-surgery, 12 months post-surgery
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Assessment of pre-and post-treatment urinary function using the Swedish national questionnaires (electronic patient-reported outcome measurements -ePROM "Symtom- och biverkningsenkät" that all patients undergoing prostate cancer treatment in Sweden routinely are invited to answer), where urinary continence is assessed using the question "How many protective pads do you use daily due to urine leakage?" The reply alternatives are: None Fewer than 1 per day About 1 per day About 2 per day About 3-4 per day About 5 or more per day |
Pre-surgery (day 80-119), 3 months post-surgery, 12 months post-surgery
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Patient-reported erectile function
大体时间：Pre-surgery (day 80-119), 3 months post-surgery, 12 months post-surgery
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Assessment of pre-and post-treatment erectile function using the Swedish national questionnaires (electronic patient-reported outcome measurements -ePROM "Symtom- och biverkningsenkät" that all patients undergoing prostate cancer treatment in Sweden routinely are invited to answer), where erectile function is assessed using the question "How would you describe your erection?" The reply alternatives are: No noticeable filling or firmness Some filling, but not sufficient for full function Moderate firmness Full firmness |
Pre-surgery (day 80-119), 3 months post-surgery, 12 months post-surgery
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MRI tumor response
大体时间：Pre-surgery (day 90-120)
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Change in tumor size and Extraprostatic Extension (EPE) score (Likert scale 1-5) on MRI compared to baseline MRI
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Pre-surgery (day 90-120)
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合作者和调查者
合作者
调查人员
- 首席研究员：Peter N Wiklund, MD, Professor、Region Stockholm represented by Karolinska University Hospital
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- 5.1.1-2025-027483
- 2025-520639-17-00 (克蒂斯)
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
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