Prostate-only, Dose-escalated Radiotherapy Plus Concomitant Androgen Deprivation Therapy in Primary Localized, NCCN High Risk and MMAI Classifier Low or Intermediate-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
- 2
- 主要终点
- Disease-free survival 5 years after treatment
研究概览
简要总结
The aim of this prospective, single-arm phase II study is the individualization of both radiotherapy (RT) and androgen deprivation therapy (ADT) duration for patients with high-risk localized prostate cancer (PCa) according to the National Comprehensive Cancer Network (NCCN) based on multimodal artificial intelligence (MMAI) classification. 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.
详细描述
In Cyprus approximately 800 men are newly diagnosed with PCa every year. Prostate cancer caused 6.1 million disability-adjusted life-years (DALYs) globally in 2016. The socio-economic burden is high since PCa-related life-time costs are approximately 40,000 per patient with early stage disease at initial diagnosis.
This is a prospective, single-center phase II trial. Patient participants will receive treatment for prostate +-seminal vesicles base high-dose-rate brachytherapy (HDR BT) with 15 Gray units (Gy) with minimal dose covering 90% of the prostate (D90) / 1 fraction followed by stereotactic body radiation therapy (SBRT) with 25 Gy in 5 Gy / fraction (daily); of the prostate +- seminal vesicles. Concomittant/adjuvant admission of 12 months ADT.
First: 1 fraction HDR BT including fiducial placement Second: 14 ±2 days gap Third: 5 fractions of SBRT within 5 consecutive weekdays For the HypoPro patients, we expect no significant differences in disease-free survival (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 basis 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 2-3 years) in this highly selected treatment group: NCCN high-risk, prostate-specific membrane antigen (PSMA) positron emission tomography (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-risk according to NCCNv4.2023 criteria (cT3a or Grade group 4-5 or PSA > 20 ng/ml)
- •Signed written informed consent for this study
- •Age >18 years
- •Previously conducted PSMA-PET/CT, mpMRI or PSMA-PET/MR
- •MMAI low-/intermediate-risk
- •ECOG Performance score 0 or 1
- •IPSS Score ≤15
- •Prostate biopsy core with the highest ISUP grade available
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 therapy, ADT 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 anaesthesia)
- •Contraindication to Goserelin
- •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
- •Patients expected to have severe set up problems (e.g. mental condition)
研究组 & 干预措施
Single experimental arm
Prostate +/-seminal vesicles base HDR BT with 15 Gy (D90) / 1 fraction followed by SBRT with 25 Gy in 5 Gy / fraction (daily); of the prostate +- seminal vesicles. Concomittant/adjuvant admission of 12 months ADT.
干预措施: Androgen deprivation therapy (ADT) (Drug)
结局指标
主要结局
Disease-free survival 5 years after treatment
时间窗: Five years
Disease recurrence is defined as PSA failure according to Phoenix, new lesions on PSMA PET and/or MRI imaging or the beginning of any salvage therapy.
次要结局
- GU acute toxicities(During, at 1 and 3 months after RT)
- Testosterone recovery(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))
- Time to local or regional failure, after end of RT(Two and five years after RT)
- Biochemical failure(Two and five years after RT)
- Gastrointestinal (GI) acute toxicities(During, 1 and 3 months after RT)
- Metastatic free survival (MFS) after end of RT(Two and five years after RT)
- GU chronic toxicities(during, 1 and 3 months after RT)
- GI acute toxicities(During, at 1 and 3 months after RT)
- Overall survival (OS)(Assessment at 1, 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54 and 60 months after RT)
- Prostate cancer specific survival (PCSS)(Assessment at 1, 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54 and 60 months after RT)
- Genitourinary (GU) acute toxicities(During, at 1 and 3 months after RT)
- Quality of Life (QoL)(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))
- GI chronic toxicities(Assessment at 6, 9, 12, 18, and 24 months after RT)
- GU chronic toxicities(During, at 1 and 3 months after RT)