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
調査の概要
詳細な説明
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.
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究連絡先
- 名前：Per H Vincent, MScEng, PhD
- 電話番号：+46(0)708239320
- メール：per.vincent@regionstockholm.se
研究連絡先のバックアップ
- 名前：Sara Göransson, PhD
- 電話番号：+46(0)812377000
- メール：sara.goransson@regionstockholm.se
研究場所
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Gothenburg、スウェーデン
- 募集
- Sahlgrenska University Hospital
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コンタクト：
- Johan Stranne, MD, Professor
- 電話番号：+46(0)709558865
- メール：johan.stranne@vgregion.se
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主任研究者：
- Johan Stranne, MD, Professor
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Stockholm、スウェーデン、SE-17176
- 募集
- Karolinska University Hospital
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コンタクト：
- Johan Björklund, MD, PhD
- 電話番号：+46(0)709583113
- メール：johan.bjorklund@regionstockholm.se
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コンタクト：
- Axel Möller, MD, PhD
- 電話番号：+46(0)706271734
- メール：axel.moller@regionstockholm.se
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主任研究者：
- Johan Björklund, MD, PhD
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参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：他の
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：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.
他の名前：
Robot-assisted radical prostatectomy, with or without extirpation of pelvic lymph nodes according to clinician's choice in concordance with local guidelines
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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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)
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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The association between PCAI ImmunoScore and pathologic complete response (pCR)
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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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協力者と研究者
スポンサー
協力者
捜査官
- 主任研究者：Peter N Wiklund, MD, Professor、Region Stockholm represented by Karolinska University Hospital
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 5.1.1-2025-027483
- 2025-520639-17-00 (Ctis)
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