Whole-pelvis Hypofractionated Radiotherapy Combined with Dose-escalation to the Prostate and Androgen Deprivation Therapy in Primary Localized, NCCN and MMAI High-risk Prostate Cancer - a Prospective, Single-arm, Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- cumulative GU toxicity
研究概览
简要总结
A prospective, phase II study applying Artificial Intelligence aiming at individualization of Radiotherapy and Androgen Deprivation Therapy duration for patients with Prostate Cancer. All patients will be treated using (i) an increased dose to the prostate (HDR brachytherapy), (ii) twelve months of ADT and (iii) extremely hypofractionated RT to the prostate (5 fractions). This way, patients will receive a prostate-only dose escalation and benefit from shortening of the ADT compared with current guideline recommendations.
详细描述
Prostate cancer (PCa) is the most frequent diagnosed malignancy in male patients in Europe and radiation therapy (RT) is a main treatment option. For primary high-risk localized PCa patients, NCCNv4.2022 guidelines recommend normo- or hypofractionated RT to the prostate and systemic treatment in terms of ADT. The benefit of two different ways to escalate RT is controversially discussed: (i) an RT dose escalation using brachytherapy (1) or focal dose escalated RT (2) or (ii) an elective RT of the pelvic lymph nodes (3). In parallel, recent studies suggest a reduction in treatment fractions in terms of ultra-hypofractionated RT(4).
The aim of this prospective, single-arm phase II study is the individualization of both RT and ADT duration for patients with NCCN high-risk localized PCa based on MMAI. All patients will receive (i) a dose escalation to the prostate via HDR brachytherapy (boost), (ii) twelve months of ADT and (iii) extremely hypofractionated RT to the prostate (5 fractions). This way, patients in the HypoPro trial will receive a prostate-only dose escalation and benefit from shortening of the ADT compared with current guideline recommendations.
For the HypoPro patients, we expect no significant differences in DFS rates compared to the FLAME trial (2) which one arm treated the patients with moderately-hypofractionated RT to the prostate plus dose escalation to the intraprostatic tumor plus 18-24 months of ADT. Secondary endpoints like metastatic free survival, prostate cancer survival and overall survival will depict the oncologic efficacy in this patient cohort. Thus, the results of this study might be used as the fundament for a randomized-controlled trial comparing this dose escalated radiotherapy plus shortened ADT duration with the standard of care (no dose escalated RT, ADT for 1-3 years) in this highly selected treatment group: NCCN high-risk, PSMA PET cN0/cM0 and MMAI low/intermediate-risk. Considering the epidemiological importance of the PCa, these results could have a significant socio-economic impact. In parallel a translational research program will address the identification of novel biomarkers to predict the treatment outcome.
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
- •Histologically confirmed adenocarcinoma of the prostate (histological confirmation can be based on tissue taken at any time, but a re-biopsy should be considered if the biopsy is more than 12 months old)
- •Primary PCa (in PSMA-PET imaging and multiparametric magnetic resonance imaging (mpMRI)
- •High- or very high-risk according to NCCNv1.2023 criteria
- •Signed written informed consent for this study
- •Age >18 years
- •Previously conducted PSMA-PET/CT, mpMRI or PSMA-PET/MR
- •MMAI high-risk
- •ECOG Performance score 0 or 1
- •IPSS Score ≤15
排除标准
- •Prior radiotherapy to the prostate or pelvis
- •Prior radical prostatectomy
- •Prior focal therapy approaches to the prostate
- •Evidence of pelvic nodal disease (cN+) in mpMRI and/or PSMA-PET/CT
- •Evidence of distant metastatic disease (cM+) in mpMRI and/or PSMA-PET/CT
- •Time gap between the beginning of any systemic therapyADT and conduction of PSMA-PET scans is >2 months
- •Evidence of cT4 disease in mpMRI and/or PSMA-PET/CT
- •PSA >50 ng/ml prior to starting of systemic therapy
- •Expected patient survival <5 years
- •Bilateral hip prostheses or any other implants/hardware that would introduce substantial CT artifacts
- •Contraindication to undergo a MRI scan
- •Contraindication to undergo HDR brachytherapy (brachytherapy not feasible due to large prostate volume, prostate anatomy, tumor in distant seminal vesicles and/or unfit for anesthesia)
- •Prostate surgery (TURP or HOLEP) with a significant tissue cavity or prostate surgery (TURP or HOLEP) within the last 6 months prior to randomization
- •Medical conditions likely to make radiotherapy inadvisable e.g. acute inflammatory bowel disease, hemiplegia or paraplegia
- •Previous malignancy within the last 2 years (except basal cell carcinoma or squamous cell carcinoma of the skin), or if previous malignancy is expected to significantly compromise 5 year survival
- •Any other contraindication to external beam radiotherapy (EBRT) to the pelvis
- •Participation in any other interventional clinical trial within the last 30 days before the start of this trial
- •Simultaneous participation in other interventional trials which could interfere with this trial; simultaneous participation in registry and diagnostic trials is allowed
- •Patient without legal capacity who is unable to understand the nature, significance and consequences of the trial
- •Known or persistent abuse of medication, drugs or alcohol
研究组 & 干预措施
Single experimental arm
RT prostate (HDR brachytherapy): 15 Gy (D90) in 1 fraction HDR RT prostate
EBRT elective pelvis (Ultra-hypofractionated RT - UHF): 25 Gy in 5 Gy per fraction
Technique: IMRT/IGRT/HDR brachytherapy
Duration: 6 fractions, 3 weeks
Androgen deprivation therapy (ADT) - Goserelin: all patients receive ADT; luteinising-hormone-releasing hormone agonists or antagonists for 24 months
Follow-up (FU) per patient: minimum FU time is 5 years (60 months), the study ends when the last enrolled patients reaches 60 months of FU time
Further FU: by the end of this clinical trial it will be decided whether further FU is necessary, amendment to this clinical trial protocol will be done in appropriate time
干预措施: Androgen Deprivation Therapy (ADT) - Goserelin (Drug)
Single experimental arm
RT prostate (HDR brachytherapy): 15 Gy (D90) in 1 fraction HDR RT prostate
EBRT elective pelvis (Ultra-hypofractionated RT - UHF): 25 Gy in 5 Gy per fraction
Technique: IMRT/IGRT/HDR brachytherapy
Duration: 6 fractions, 3 weeks
Androgen deprivation therapy (ADT) - Goserelin: all patients receive ADT; luteinising-hormone-releasing hormone agonists or antagonists for 24 months
Follow-up (FU) per patient: minimum FU time is 5 years (60 months), the study ends when the last enrolled patients reaches 60 months of FU time
Further FU: by the end of this clinical trial it will be decided whether further FU is necessary, amendment to this clinical trial protocol will be done in appropriate time
干预措施: High-Dose-Rate Interstitial Brachytherapy (HDR BRT) (Radiation)
Single experimental arm
RT prostate (HDR brachytherapy): 15 Gy (D90) in 1 fraction HDR RT prostate
EBRT elective pelvis (Ultra-hypofractionated RT - UHF): 25 Gy in 5 Gy per fraction
Technique: IMRT/IGRT/HDR brachytherapy
Duration: 6 fractions, 3 weeks
Androgen deprivation therapy (ADT) - Goserelin: all patients receive ADT; luteinising-hormone-releasing hormone agonists or antagonists for 24 months
Follow-up (FU) per patient: minimum FU time is 5 years (60 months), the study ends when the last enrolled patients reaches 60 months of FU time
Further FU: by the end of this clinical trial it will be decided whether further FU is necessary, amendment to this clinical trial protocol will be done in appropriate time
干预措施: radiotherapy (Radiation)
结局指标
主要结局
cumulative GU toxicity
时间窗: two years
Primary endpoint is cumulative GU toxicity according to RTOG grading after minimum FU time of two years.
次要结局
- Time to local or regional failure(two and five years after RT)
- MMAI classifier(5-year and 10-year risk prediction of distant metastasis and 10-year risk of prostate-specific mortality.)
- Testosterone(assessment at 6,9,12,18 and 24 months after randomization (± 14 days for each visit) and at 30, 36, 42, 48, 54, 60 months after Ultra-hypofractionated RT - UHF (± 1 month)
- Metastatic free survival (MFS)(two and five years after RT)
- Overall Survival (OS)(1, 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54 and 60 months after RT)
- Prostate cancer specific survival (PCSS)(1, 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54 and 60 months after RT)
- Biochemical failure(two and five years after RT)
- Quality of Life (QoL)(Assessments at 6, 9,12, 18, and 24 months after randomization (± 14 days for each visit) and at 30, 36, 42, 48, 54, 60 months after Ultra-hypofractionated RT - UHF (± 1 month))
- QoL(Assessments at 6, 9,12, 18, and 24 months after randomization (± 14 days for each visit) and at 30, 36, 42, 48, 54, 60 months after Ultra-hypofractionated RT - UHF (± 1 month))
- Genitourinary (GU) acute toxicities(during, 1 and 3 months after RT)
- GU acute toxicities(during, 1 and 3 months after RT)
- GU chronic toxicities(6, 9, 12, 18 and 24 months after RT)
- Gastrointestinal (GI) acute toxicities(during, 1 and 3 months after RT)
- GI acute toxicities(during, 1 and 3 months after RT)
- GI chronic toxicities(6, 9, 12, 18 and 24 months after RT)
- Dose contrainsts(during, 1 and 3 months after RT)