A Prospective Study Based on Spatial Multi-Omics for Predicting the Efficacy of Androgen Deprivation Therapy Combined With Second-Generation Novel Endocrine Therapeutic Agents in Metastatic Hormone-Sensitive Prostate Cancer.
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Biochemical Progression-Free Survival (bPFS)
研究概览
简要总结
This study plans to enroll patients with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) and conduct a prospective, single-center, observational study. By performing whole-exome sequencing (WES), Xenium spatial transcriptomics, and PhenoCycler-Fusion spatial single-cell proteomics (PCF analysis) on tumor tissue samples, we aim to comprehensively delineate the molecular landscape of patients with different spatial multi-omic profiles in the real-world setting. We will investigate the associations between these molecular features and differential treatment responses to various therapeutic regimens, and further construct predictive models of treatment response. Ultimately, this will enable precise evaluation of treatment outcomes across distinct molecular subtypes and provide evidence to support individualized precision diagnostics and therapeutics for patients with mHSPC.
详细描述
1、Baseline sample collection: Tumor tissues will be collected via prostate biopsy from enrolled patients. The specimens will be tripartite: one aliquot for standard histopathology, one for WES, and one for spatial multi-omic profiling (Xenium and PhenoCycler-Fusion).2、Follow-up: Patients will be assessed every 3 months during therapy, with CBC, biochemistry, sex hormones, and serum PSA. Prostate mpMRI will be repeated every 3 months. PSA testing frequency may be modified if PSA progression occurs. Follow-up continues until CRPC development or death.3、（1）Primary: Build a prognostic model integrating Xenium, WES, and PCF data.（2）Secondary: bPFS and OS.（3）Progression: PSA rise to ≥0.2 ng/mL confirmed on repeat testing after prior undetectable levels.
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 85 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Age > 18 years and < 85 years.
- •Histopathologically confirmed prostate adenocarcinoma, ductal adenocarcinoma, or intraductal carcinoma.
- •Imaging evidence of definite distant metastases (according to RECIST criteria).
- •Pre-biopsy PSA ≥ 20 ng/mL or Gleason score ≥ 4+
- •No prior hormonal therapy or other systemic anti-tumor regimens.
- •ECOG performance status 0-2, with an estimated life expectancy > 6 months.
- •Adequate organ function.h. Ability and willingness to provide written informed consent, and capability to comply with the study visit schedule.
排除标准
- •Histopathological diagnosis of neuroendocrine or small cell prostate cancer.
- •No definite distant metastases detected on imaging.
- •Prior history of anti-tumor therapy (including neoadjuvant, adjuvant, or other treatments).
- •Submitted biopsy samples fail to meet quality control requirements.
- •Concurrent severe endocrine or metabolic disorders, or other severe digestive system diseases.
- •Concurrent chronic hepatitis, cirrhosis, chronic nephritis, renal insufficiency, or other relevant conditions.
- •History of immunodeficiency or organ transplantation.
- •History of other concurrent malignancies.
- •Concurrent enrollment in other clinical trials.
- •Other conditions that the investigator deems unsuitable for study enrollment.
研究组 & 干预措施
Newly diagnosed mHSPC patients who meet the inclusion criteria
Eligible patients will be enrolled after providing written informed consent. Individualized therapy (ADT plus abiraterone or other ARPIs) will be prescribed by the investigators according to each patient's financial situation, drug availability, and clinical needs, with regular follow-ups performed following routine real-world practice
干预措施: ADT plus abiraterone or other ARPIs（apalutamide, enzalutamide, rezvilutamide, darolutamide) (Drug)
结局指标
主要结局
Biochemical Progression-Free Survival (bPFS)
时间窗: From treatment initiation until biochemical progression or last follow-up, assessed every 3 months (±1 month) for up to 24 months.
Time from initiation of ADT plus ARPI therapy to biochemical progression or death from any cause, whichever occurs first. Biochemical progression is defined as a PSA rise to ≥0.2 ng/mL after having reached an undetectable level, confirmed by a second measurement at least 2 weeks apart. Participants without an event will be censored at the date of last follow-up.
Overall Survival (OS)
时间窗: From treatment initiation until death or last follow-up, assessed up to 24 months.
Time from treatment initiation to death from any cause. Participants alive or lost to follow-up will be censored at the date last known alive.
次要结局
- Mutation Frequency of Key Genes Assessed by Whole-Exome Sequencing (WES)(Baseline (at enrollment, from biopsy tissue).)
- Spatial Gene Expression Signatures Measured by Xenium Platform(Baseline (at enrollment).)
- Spatial Protein Marker Expression Measured by PhenoCycler-Fusion (PCF)(Baseline (at enrollment).)
- Area Under the Receiver Operating Characteristic Curve (AUC) of the Multi-omics Prediction Model for 6-Month Undetectable PSA（ PSA <0.2 ng/mL ）(Baseline data used to predict outcome at 6 months after treatment initiation.)
研究者
Sheng Tai
the chief of the ward
Anhui Medical University