POLO-Trial. Precise Neoadjuvant Chemoresection of Low-grade NMIBC Guided by Drug Sceens in Patient-derived Or-ganoids. An Open-label, Phase II Trial.
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 28
- 试验地点
- 3
- 主要终点
- Pathological response
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- All
- 接受健康志愿者
- 否
入选标准
- •Signed Informed Consent Form
- •Age ≥ 18 years
- •Primary or recurrent NMIBC suspected to be low-grade or maximum G2 with a negative urine cytology
排除标准
- •Anticoagulation other than acetylsalicylic acid
- •Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol as judged by the investigator
- •Severe infection within 4 weeks prior to the date of the patient's informed consent signature
- •Contraindication for frequent catheterization
- •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
- •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
- •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
- •Vulnerable individual, e.g., individual incapable of judgement or currently incarcerated or oth-erwise institutionalized (prisoner), or refugee
- •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.
研究组 & 干预措施
Epirubicin
Patients in that PDOs show highest response to this drug in-vitro will be treated with Epirubicin.
干预措施: Epirubicin (Drug)
Docetaxel
Patients in that PDOs show highest response to this drug in-vitro will be treated with Docetaxel.
干预措施: Docetaxel (Drug)
Gemcitabine
Patients in that PDOs show highest response to this drug in-vitro will be treated with Gemcitabine.
干预措施: Gemcitabine (Drug)
Mitomycin
Patients in that PDOs show highest response to this drug in-vitro will be treated with Mitomycin.
干预措施: Mitomycin (Drug)
结局指标
主要结局
Pathological response
时间窗: 15 weeks
Rate of patients that show complete pathological response to neoadjuvant chemoresection
次要结局
- Number of patients with recurrence free survival(1 Year)
- Tolerability of instillation(15 weeks)
- Feasibility of drug screen(4 weeks)
- Safety of the study intervention(12 weeks)
- Tolerability of instillation(24 weeks)