ChiCTR2400094624 版本V1.0 版本创建时间2024/12/25 11:32:05 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

ChiCTR2400094624 

最近更新日期：

Date of Last Refreshed on：

2024-12-25 11:31:16 

注册时间：

Date of Registration：

2024-12-25 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

新发高瘤负荷mHSPC在ADT联合NHT转化治疗后进行残留病灶全覆盖局部治疗的效果：一项前瞻性单臂临床研究

Public title：

The Effect of Comprehensive Cytoreductive Treatment for Residual Lesions in Newly Diagnosed High-Tumor-Burden Metastatic Hormone-Sensitive Prostate Cancer after Triplet or Doublet Conversion Therapy: A Prospective Single-Arm Clinical Study

注册题目简写：

English Acronym：

研究课题的正式科学名称：

新发高瘤负荷mHSPC在ADT联合NHT转化治疗后进行残留病灶全覆盖局部治疗的效果：一项前瞻性单臂临床研究

Scientific title：

The Effect of Comprehensive Cytoreductive Treatment for Residual Lesions in Newly Diagnosed High-Tumor-Burden Metastatic Hormone-Sensitive Prostate Cancer after Triplet or Doublet Conversion Therapy: A Prospective Single-Arm Clinical Study

研究课题代号(代码)：

Study subject ID：

在二级注册机构或其它机构的注册号：

The registration number of the Partner Registry or other register：

申请注册联系人：

杨斌 

研究负责人：

杨斌 

Applicant：

Bin Yang 

Study leader：

Bin Yang 

申请注册联系人电话：

Applicant telephone：

+86 159 2199 9859

研究负责人电话：

Study leader's telephone：

+86 159 2199 9859

申请注册联系人传真 ：

Applicant Fax：

研究负责人传真：

Study leader's fax：

申请注册联系人电子邮件：

Applicant E-mail：

yangbin710@163.com

研究负责人电子邮件：

Study leader's E-mail：

yangbin710@163.com

申请单位网址(自愿提供)：

Applicant website(voluntary supply)：

研究负责人网址(自愿提供)：

Study leader's website(voluntary supply)：

申请注册联系人通讯地址：

上海市延长中路301号

研究负责人通讯地址：

上海市延长中路301号

Applicant address：

301 Middle Yanchang Road, Jing'an District, Shanghai, China

Study leader's address：

301 Middle Yanchang Road, Jing'an District, Shanghai, China

申请注册联系人邮政编码：

Applicant postcode：

研究负责人邮政编码：

Study leader's postcode：

申请人所在单位：

上海市第十人民医院

Applicant's institution：

Shanghai Tenth People's Hospital

研究负责人所在单位：

上海市第十人民医院

Affiliation of the Leader：

Shanghai Tenth People's Hospital

是否获伦理委员会批准：

是/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

SHSY-IEC-5.0/24KY28/P02

伦理委员会批件附件：

Approved file of Ethical Committee：

 查看附件View

批准本研究的伦理委员会名称：

上海市第十人民医院伦理委员会

Name of the ethic committee：

Ethics Committee of Shanghai Tenth People’s Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

2024-10-21 00:00:00

伦理委员会联系人：

孙奋勇

Contact Name of the ethic committee：

Fenyong Sun

伦理委员会联系地址：

上海市延长中路301号

Contact Address of the ethic committee：

301 Middle Yanchang Road, Jing'an District, Shanghai, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 21 6630 1604

伦理委员会联系人邮箱：

Contact email of the ethic committee：

研究实施负责（组长）单位：

上海市第十人民医院

Primary sponsor：

Shanghai Tenth People's Hospital

研究实施负责（组长）单位地址：

上海市延长中路301号

Primary sponsor's address：

301 Middle Yanchang Road, Jing'an District, Shanghai, China

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

上海

市(区县)：

Country：

China

Province：

Shanghai

City：

单位(医院)：

上海市第十人民医院

具体地址：

上海市延长中路301号

Institution
hospital：

Shanghai Tenth People's Hospital

Address：

301 Middle Yanchang Road, Jing'an District

经费或物资来源：

国家卫生健康委医药卫生科技发展研究中心

Source(s) of funding：

Development Center for Medical Science & Technology National Health Commission of the People's Republic of China

Target disease：

prostate cancer

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 II期临床试验 

Study phase：

2

研究设计：

横断面 

Study design：

Cross-sectional 

研究目的：

主要研究目的包括：明确高瘤负荷mHSPC患者接受转化治疗联合残留病灶全覆盖局部治疗的有效性；探索与转化治疗联合局部治疗的预后相关的影响因素，筛选可通过该治疗方案获得最大生存收益的患者亚群。并通过收集患者初诊和治疗后肿瘤组织/血液样本，探索基于深度二代测序的分子分型，以及病理组学和PSMA-PET/CT影像组学特征和衍生参数对此类前列腺癌患者PSA反应及预后评估的指导意义。  

Objectives of Study：

The main objectives of this study were to clarify the efficacy of conversion therapy combined with local treatment with full coverage of residual lesions in mHSPC patients with high tumor burden; To explore the prognostic factors associated with conversion therapy combined with local therapy, and to screen the patient subgroups that can obtain the greatest survival benefit from this treatment. By collecting tumor tissue/blood samples of patients at initial diagnosis and after treatment, the guiding significance of molecular typing based on deep next-generation sequencing, pathomics and PSMA-PET/CT radiomics features and derived parameters in PSA response and prognosis evaluation of these patients was explored.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

(1) 男性，年龄18周岁及以上，ECOG评分0分； (2) 组织学或细胞学证实的前列腺腺癌（不允许原发性前列腺小细胞癌或印戒细胞癌，但允许有神经内分泌分化≤10%的腺癌），且初诊病理组织可获取； (3) 新诊断前列腺癌（入组前3个月内）； (4) 入组时通过常规影像学技术（CT，MRI和骨扫描）和PSMA-PET/CT评估患者的原发灶和转移灶； (5) 入组前未接受过任何形式的局部治疗，允许入组前接受过ADT或第一代抗雄激素药物（如比卡鲁胺、氟他胺）≤4周； (6) 在接受转化治疗前的6周内接受PSMA-PET/CT检查，由高年资影像科专科医生确定患者处于高瘤负荷阶段：≥4处骨转移灶（其中至少1个骨转移位于盆腔或脊柱以外）或出现内脏转移； (7) 同意接受ADT（GnRHa激动剂或GnRHa拮抗剂）联合NHT的转化治疗（每个治疗周期为28天，共6个治疗周期，联合或不联合6周期多西他赛化疗），具体方案、频率和剂量由研究者决定，如果发生不良事件，根据说明书调整剂量。方案包括： a)ADT+NHT b)ADT+NHT+多西他赛6周期化疗 (8) 同意在转化治疗完成6个周期后的4至6周内接受PSMA-PET/CT的再次评估，且愿意在前列腺癌多学科团队共同评估符合寡残留前列腺癌标准且可耐受进一步减瘤治疗的情况下，进一步接受针对残留病灶的全覆盖局部治疗（cRP和/或PLND±放疗）。对于手术患者，ADT在整个围手术期维持，NHT在手术后2周内停用，NHT将在手术后2周后恢复。 寡残留前列腺癌定义为：在PSMA-PET/CT评估下存在1-3处骨转移灶，允许存在区域淋巴结转移灶（腹主动脉分叉及以下的盆腔范围内的淋巴结转移）。针对寡残留病灶，在局部治疗前均有传统影像学的检查结果，作为治疗后随访时的对比资料。 a) cRP是标准的根治性前列腺精囊切除，可以通过开放手术，腹腔镜手术和机器人手术完成； b) PLND包括：清扫范围至少包括闭孔区域，髂内区域，髂外区域；必要时包括髂总区域和骶前区域（存在可手术的PSMA-PET/CT阳性病灶）； c) 根据前列腺癌多学科团队共同决策，可进行盆腔放疗作为减瘤治疗，包括针对前列腺精囊和区域淋巴结以及盆腔淋巴引流区的放疗； d) 根据前列腺癌多学科团队共同决策，可在PSMA-PET/CT引导下针对转移灶的根治剂量的放疗（包括采用常规分隔和大分割的SBRT等放疗技术）； e) 在接受cRP后有需要盆腔放疗（包括瘤床和盆腔淋巴引流区）的患者，在cRP手术后3至6个月，控尿恢复后，进行盆腔放疗； f) 对于接受放疗的患者，ADT联合NHT在放疗期间维持；放疗的剂量计划和方案，根据不同部位病灶和周围正常组织的耐受水平而变化； g) 整个减瘤治疗的周期不超过10个月。 (9) 患者本人或患者授权的直系亲属已签署临床试验知情同意书。

Inclusion criteria

(1) Male, aged 18 years and above, ECOG score 0; (2) histologically or cytologically confirmed prostate adenocarcinoma (small-cell or signet-ring cell primary prostate cancer was not allowed, but adenocarcinoma with neuroendocrine differentiation <=10% was allowed), with available pathological tissue at initial diagnosis; (3) newly diagnosed prostate cancer (within 3 months before enrollment); (4) Primary and metastatic lesions were evaluated by conventional imaging techniques (CT, MRI and bone scan) and PSMA-PET/CT at enrollment. (5) Patients had not received any form of local treatment before enrollment, and ADT or first-generation antiandrogen drugs (such as bicalutamide and flutamide) were allowed to be received for <=4 weeks before enrollment; (6) PSMA-PET/CT was performed within 6 weeks before conversion therapy, and the patients were classified as having a high tumor burden as defined by a senior imaging specialist: >=4 bone metastases (at least one bone metastasis outside the pelvis or spine) or visceral metastases; (7) Consent to conversion therapy with ADT (GnRHa agonist or GnRHa antagonist) plus NHT (six 28-day cycles per treatment, with or without six cycles of docetaxel chemotherapy), with protocol, frequency, and dose determined by the investigator, with dose adjustment according to the label in case of adverse events. The programme includes: a) ADT+NHT b) ADT+NHT+ 6 cycles of docetaxel chemotherapy (8) agree to undergo PSMA-PET/CT reassessment within 4 to 6 weeks after the completion of six cycles of conversion therapy, and are willing to be evaluated by a multidisciplinary prostate cancer team if they meet the criteria for minimal residual prostate cancer and can tolerate further cytoreductive therapy; Patients were further treated with full-coverage local treatment (cRP and/or PLND+/- radiotherapy) for residual lesions. For surgical patients, ADT is maintained throughout the perioperative period, NHT is discontinued within 2 weeks after surgery, and NHT will be resumed after 2 weeks after surgery. Minimal residual prostate cancer was defined as the presence of 1-3 bone metastases as assessed by PSMA-PET/CT, and regional lymph node metastases (lymph node metastases in the pelvic area and below the abdominal aortic bifurcation) were allowed. For the oligo-residual lesions, the results of traditional imaging examination were available before local treatment, which were used as comparison data during follow-up after treatment. a) cRP is the standard radical prostatectomy and can be performed by open surgery, laparoscopic surgery and robotic surgery; b) PLND includes: the scope of dissection includes at least the obturator region, internal iliac region, and external iliac region; If necessary, the common iliac region and presacral region (with operable PSMA-PET/CT positive lesions) were included; c) According to the shared decision of the multidisciplinary team of prostate cancer, pelvic radiotherapy can be performed as tumor-reducing treatment, including radiotherapy to the prostate seminal vesicle and regional lymph nodes, and pelvic lymphatic drainage area; d) the definitive dose of PSMA-PET/ CT-guided radiotherapy (including conventionally fractionated and hypofractionated SBRT) for metastatic lesions based on the shared decision of the prostate cancer multidisciplinary team; e) for patients requiring pelvic radiotherapy (including the tumor bed and pelvic lymphatic drainage area) after cRP, pelvic radiotherapy was performed 3 to 6 months after cRP surgery, after recovery of urinary control; f) For patients receiving RT, ADT plus NHT was maintained during RT; The dose plan and protocol of radiotherapy vary according to the tolerance level of different lesions and surrounding normal tissues. g) The entire cycle of cytoreductive therapy should not exceed 10 months. (9) Patients or their authorized immediate family members had signed the informed consent for the clinical trial.

排除标准：

(1)预期寿命小于1年； (2)具有严重精神疾病或者有其他原因导致无法配合规范治疗或随访； (3)患有其他肿瘤性疾病； (4)对促性腺素释放素（GnRH）类似物严重过敏； (5)接受免疫抑制治疗或有免疫缺陷疾病； (6)严重的肝功能损害（Child-Pugh C级）； (7)严重的肾功能损伤需要长期行透析治疗； (8)严重的骨髓抑制、重度中性粒细胞减少症； (9)不能耐受手术或放疗； (10)自入组前30天至本研究完成期间参与其他的临床研究。

Exclusion criteria：

(1) life expectancy less than 1 year; (2) Unable to cooperate with standard treatment or follow-up due to severe mental illness or other reasons; (3) patients with other neoplastic diseases; (4) severe allergy to gonadotropin-releasing hormone (GnRH) analogues; (5) patients with immunosuppressive therapy or immunodeficiency diseases; (6) severe liver function impairment (Child-Pugh grade C); (7) Severe renal dysfunction requiring long-term dialysis; (8) severe bone marrow suppression and severe neutropenia; (9) patients could not tolerate surgery or radiotherapy; (10) Participating in other clinical studies from 30 days before enrollment until the completion of the study.

研究实施时间：

Study execute time：

从 From 2025-01-01 00:00:00至 To 2026-10-31 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2025-01-01 00:00:00 至 To 2026-10-31 00:00:00  

干预措施：

Interventions：

组别：

试验组

样本量：

60

Group：

Experimental Group

Sample size：

干预措施：

针对ADT联合NHT治疗后PSMA PET识别的残留病灶的全覆盖局部治疗（包括cRP，PLND以及放疗）

干预措施代码：

Intervention：

Comprehensive cytoreductive treatment (including cRP, PLND, and radiotherapy) for residual disease identified by PSMA PET after ADT plus NHT

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 上海 

市(区县)：

  

Country：

China 

Province：

Shanghai 

City：

 

单位(医院)：

上海市第十人民医院 

单位级别：

三甲 

Institution
hospital：

Shanghai Tenth People’s Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

影像学无进展生存

指标类型：

主要指标

Outcome：

radiographic progression-free survival, rPFS

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

病理完全缓解率

指标类型：

次要指标

Outcome：

pathological complete response rate, pCR rate

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

至PSA进展时间

指标类型：

次要指标

Outcome：

time to PSA progression

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

总生存

指标类型：

次要指标

Outcome：

overall survival, OS

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

转化治疗6个周期完成后，经前列腺癌多学科团队共同评估，符合寡残留前列腺癌且可实施全覆盖局部治疗的患者比例

指标类型：

次要指标

Outcome：

After the completion of 6 cycles of conversion therapy, the proportion of patients with oligo-residual prostate cancer who could be treated with comprehensive cytoreductive treatment as assessed by the multidisciplinary team of prostate cancer

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

转化治疗6个周期完成后，达到PSA50/PSA90以及PSA下降至≤0.2ng/ml的患者百分比。PSA50和PSA90缓解率分别是较初诊治疗前降低超过50%和90%的患者百分比

指标类型：

次要指标

Outcome：

The percentage of patients achieving PSA50/PSA90 and PSA reduction to ≤0.2ng/ml after 6 cycles of conversion therapy. The PSA50 and PSA90 response rates were the percentages of patients who had a reduction of more than 50% and 90%, respectively, from the time before initial treatment

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

前列腺癌组织

组织：

Sample Name：

Prostate Cancer tissue

Tissue：

人体标本去向

 使用后销毁  

说明

Fate of sample：

Destruction after use  

Note：

征募研究对象情况：

Recruiting status：

正在进行

Recruiting

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age - 岁 years

性别：

男性

Gender：

Male

随机方法（请说明由何人用什么方法产生随机序列）：

无

Randomization Procedure (please state who generates the random number sequence and by what method)：

None

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：

无

Blinding：

None

试验完成后的统计结果（上传文件）：

Calculated Results after
the Study Completed(upload file)：

是否共享原始数据：

IPD sharing

Yes

共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：

本研究将在试验完成后的6个月内公开原始数据, 可以向研究者邮件索取试验原始数据。

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：

The original data will be publicly available within 6 months after the completion of the trial. The original data can be requested by email from the investigators.

数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：

有纸质病历档案和电子病例记录表，并根据病例记录表的项目采用Excel软件建立相应的数据库录入程序，设定录入时的逻辑审查限定条件，对病例数据库进行运行和管理，进而实现本临床试验数据的采集和管理。

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：

The medical reports of each participant will be completely collected and recorded in the database established in EXCEL softare, so that the data can be easily reached and managed.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

暂未确定/Not yet

注册人：

Name of Registration：

  2024-12-25 11:31:16