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低级别 NMIBC 的精确新辅助化疗切片 (POLO)

2026年9月15日 更新者：Hospital Centre Biel/Bienne

在患者衍生类器官中以药物筛选为指导对低级别 NMIBC 进行精确新辅助化学切片：单中心、开放标签、II 期试验

Based on the unmet clinical need to reduce invasiveness of treatment of low grade NMIBC, the investigators conduct this prospective, open label, single arm and single center phase II trial. The investigators aim to use drug screens in PDOs to guide neoadjuvant intravesical instillation therapy with either Epirubicin, Mitomycin C, Gemcitabine or Docetaxel to achieve chemoresection NMIBC.

研究概览

地位

尚未招聘

条件

干预/治疗

详细说明

Bladder cancer is a disease of the elderly patient and related to several interventions and operations. Patients with a low risk non-muscle invasive bladder cancer (NMIBC) are treated by transurethral resection of the bladder tumor (TURBT). Due to the high recurrence rate of approximately 50% within 2 years of diagnosis, patients are followed in outpatient clinic by cystoscopy for at least 5 years.

Beside recurrence of low grade NMIBC to low grade disease, progression to higher grade or stage is infrequent to rare. Therefore, expectant management and actives surveillance seems to be an option for selected patients that are unfit for surgery. Moreover, intravesical chemoresection has been attempted in order to avoid surgery. However, all patients were treated with the same chemotherapeutic agent and anticipated response rates were missed.

At least four different drugs have been used in daily routine and/or clinical trials for instillation therapies in NMIBC. Namely, Epirubicin, Mitomycin C, Gemcitabine and Docetaxel have been investigated and administered.

The molecular landscape of NMIBC is heterogeneous. Not only the mutational pattern but also the transcriptomic characteristics vary between different NMIBC. Although different agents are used on a routine daily bases and in clinical trials, they have not been administered based on the molecular landscape or biological likelihood of response.

The investigators recently developed a pipeline for the generation of patient derived organoids (PDO) in NMIBC. In brief: The bladder cancer is sampled during TURBT. Generation of organoids has been carefully optimized in order to yield high viability from each sample. Beside confirmation of similarities of the molecular landscape between parental NMIBC and subsequent PDO (in approx. 30 samples), the investigators established a standardized protocol to perform drug screens on these PDOs.

In this trial (POLO Trial) the investigators aim to generate PDOs from bladder cancer biopsies that are harvested in the outpatient clinic. Subsequent drug screen in PDOs for Epirubicin, Mitomycin C, Gemcitabine and Docetaxel will identify the most effective agent in this given patient. Prior TURBT, patient will receive 6 intravesical instillations with the identified agent as neoadjuvant treatment in order to perform chemoresection of the tumor. Three months after initial diagnosis, TURBT will be performed as the standard treatment and to confirm response rate of precise chemoresection.

研究类型

介入性

注册 (估计的)

28

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

研究联系人备份

学习地点

  • 瑞士
      • Bern、瑞士、3001
        • Lindenhofspital, Klinik für Urologie
        • 接触：
        • 首席研究员：
          • Bernard Kiss
      • Biel、瑞士、2501

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  1. Signed Informed Consent Form
  2. Age ≥ 18 years
  3. Primary or recurrent NMIBC suspected to be low-grade or maximum G2 with a negative urine cytology

Exclusion Criteria:

  1. Anticoagulation other than acetylsalicylic acid
  2. Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol as judged by the investigator
  3. Severe infection within 4 weeks prior to the date of the patient's informed consent signature
  4. Contraindication for frequent catheterization
  5. Pregnancy or nursing. Female subject of childbearing potential (defined as premenopausal women who have not undergone surgical sterilization and are sexually active with a male part-ner) must have a negative urine pregnancy test at screening
  6. Female subject of childbearing potential who is unwilling to use effective contraception method(s) from the start of the intravesical instillation with the IMP until six months after the last instillation
  7. Male subject who is unwilling to use an effective contraception method from the start of the intravesical instillation with the IMP until four months after the last instillation
  8. Vulnerable individual, e.g., individual incapable of judgement or currently incarcerated or oth-erwise institutionalized (prisoner), or refugee
  9. Concomitant participation in another interventional clinical trial with an active treatment within 4 weeks prior to the date of the patient's informed consent signature and during the current trial.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：非随机化
  • 介入模型：单组作业
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：Epirubicin

Patients in that PDOs show highest response to this drug in-vitro will be treated with Epirubicin.
药品：Epirubicin

In PDOs from patients that show highest response to Epirubicin, this drug will be instilled intravesically once weekly for 6 times.

Epirubicin will be used as a concentrate for injection/instillation 2 mg/ml in total 50mg per vial. Prior to use, the concentrate for injection is diluted with 25ml of 0.9% saline solution to obtain the final Solution with 1mg/ml of Epirubicin.
实验性的：Mitomycin

Patients in that PDOs show highest response to this drug in-vitro will be treated with Mitomycin.
药品：Mitomycin

In PDOs from patients that show highest response to Mitomycin, this drug will be instilled intravesically once weekly for 6 times.

Mitomycin C will be used as 20mg dry powder. Prior to use, the powder will be dissolved in 50ml of 0.9% saline solution according to the manufacturer instructions
实验性的：Gemcitabine

Patients in that PDOs show highest response to this drug in-vitro will be treated with Gemcitabine.
药品：Gemcitabine

In PDOs from patients that show highest response to Gemcitabine, this drug will be instilled intravesically once weekly for 6 times.

Gemcitabine will be used as 2000 mg/50ml. For intravesical application, 1000mg of gemcitabine (corresponding to 25ml) will be diluted in 25ml 0.9% saline solution, to obtain the gemcitabine concentration of 1000mg/50ml used for instillation.
实验性的：Docetaxel

Patients in that PDOs show highest response to this drug in-vitro will be treated with Docetaxel.
药品：Docetaxel

In PDOs from patients that show highest response to Docetaxel, this drug will be instilled intravesically once weekly for 6 times.

Docetaxel will be used as 140mg/7ml solution. For intravesical application, 48.825ml of saline will be added to 1.875ml Docetaxel solution (according 37.5mg of Docetaxel). The concentration of this solution is 0.74mg/ml by a total volume of the instillation solution of 50,7.

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Pathological response
大体时间：15 weeks

Rate of patients that show complete pathological response to neoadjuvant chemoresection
15 weeks

次要结果测量

结果测量
措施说明
大体时间
Feasibility of drug screen
大体时间：4 weeks

Rate of patients in which drug screen in patient derived organoids was successful
4 weeks
Safety of the study intervention
大体时间：12 weeks

Incidence, severity and type of Adverse Events of Special Interest (AESIs) which are defined as adverse events related to chemotherapeutic intravesical instillation. AESIs include dysuria, urinary tract infections, and complications due to catheterism for intravesical instillation such as urethral irritation and haematuria
12 weeks
Number of patients with recurrence free survival
大体时间：1 Year

Recurrence after neoadjuvant chemoresection and transurethral resection of the bladder tumor
1 Year
Tolerability of instillation
大体时间：24 weeks

Quality of life measured with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). It corresponds to a functional Scales & Global Health Status; a higher score indicates a better outcome (a higher level of functioning or a better quality of life). The score minimum is 0 and maximum 100.
24 weeks
Tolerability of instillation
大体时间：24 weeks

The quality of life is completed with a Symptom & Concern Scale specific for NMIBC called European Organisation for Research and Treatment of Cancer 24-Item Non-Muscle-Invasive Bladder Cancer Module (EORTC QLQ-NMIBC24).

This Symptom & Concern Scale has also a minimum score of 0 and a maximum of 100. A higher score indicates a worse outcome (a greater burden of symptoms or high symptomatology).
24 weeks

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Hospital Centre Biel/Bienne

合作者

Lindenhofgruppe AG
Fond'action contre le cancer
Spitalzentrum Biel

调查人员

  • 学习椅：Roland Seiler, Prof.、Spitalzentrum Biel

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

2026年12月1日

初级完成 (估计的)

2030年11月30日

研究完成 (估计的)

2031年11月30日

研究注册日期

首次提交

2024年1月17日

首先提交符合 QC 标准的

2024年1月25日

首次发布 (实际的)

2024年1月26日

研究记录更新

最后更新发布 (实际的)

2026年9月18日

上次提交的符合 QC 标准的更新

2026年9月15日

最后验证

2026年9月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • SZB-URO-26-001

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

是的

IPD 计划说明

After completion of the trial for the primary endpoint, deidentified data will be shared to other researches upon request.

IPD 共享时间框架

After completion of the trial to the primary endpoint.

IPD 共享支持信息类型

  • 研究方案

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

在美国制造并从美国出口的产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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