Quimiorressecção neoadjuvante precisa de NMIBC de baixo grau (POLO)
Quimiorressecção neoadjuvante precisa de NMIBC de baixo grau guiada por triagens de drogas em organoides derivados de pacientes: um ensaio de centro único, aberto, de fase II
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.
Visão geral do estudo
Status
Intervenção / Tratamento
Descrição detalhada
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.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 2
Contactos e Locais
Contato de estudo
- Nome: Roland Seiler, Prof.
- Número de telefone: +41 32 324 32 06
- E-mail: urologie@szb-chb.ch
Estude backup de contato
- Nome: Martina Schneider
- Número de telefone: +41 323243217
- E-mail: martina.schneider@szb-chb.ch
Locais de estudo
-
-
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Bern, Suíça, 3001
- Lindenhofspital, Klinik für Urologie
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Contato:
- Bernard Kiss
- Número de telefone: +41 31 300 38 88
- E-mail: bernhard.kiss@hin.ch
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Investigador principal:
- Bernard Kiss
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Biel, Suíça, 2501
- Spitalzentrum Biel, Klinik für Urologie
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Contato:
- Martina Schneider
- Número de telefone: +41 323243217
- E-mail: martina.schneider@szb-chb.ch
-
Contato:
- Roland Seiler, Prof.
- Número de telefone: +41 32 324 32 06
- E-mail: Roland.Seiler-Blarer@szb-chb.ch
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- Signed Informed Consent Form
- Age ≥ 18 years
- Primary or recurrent NMIBC suspected to be low-grade or maximum G2 with a negative urine cytology
Exclusion Criteria:
- 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.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Epirubicin
Patients in that PDOs show highest response to this drug in-vitro will be treated with 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. |
|
Experimental: Mitomycin
Patients in that PDOs show highest response to this drug in-vitro will be treated with 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 |
|
Experimental: Gemcitabine
Patients in that PDOs show highest response to this drug in-vitro will be treated with 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. |
|
Experimental: Docetaxel
Patients in that PDOs show highest response to this drug in-vitro will be treated with 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. |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Pathological response
Prazo: 15 weeks
|
Rate of patients that show complete pathological response to neoadjuvant chemoresection |
15 weeks
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Feasibility of drug screen
Prazo: 4 weeks
|
Rate of patients in which drug screen in patient derived organoids was successful |
4 weeks
|
|
Safety of the study intervention
Prazo: 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
Prazo: 1 Year
|
Recurrence after neoadjuvant chemoresection and transurethral resection of the bladder tumor |
1 Year
|
|
Tolerability of instillation
Prazo: 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
Prazo: 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
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Cadeira de estudo: Roland Seiler, Prof., Spitalzentrum Biel
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças urogenitais
- Neoplasias urogenitais
- Neoplasias por local
- Neoplasias
- Doenças Urogenitais Masculinas
- Doenças Urológicas
- Doenças Urogenitais Femininas
- Doenças urogenitais femininas e complicações na gravidez
- Neoplasias por Tipo Histológico
- Neoplasias Glandulares e Epiteliais
- Neoplasias Urológicas
- Carcinoma
- Doenças da Bexiga Urinária
- Neoplasias Não Musculares Invasivas da Bexiga
- Neoplasias da Bexiga Urinária
- Produtos químicos orgânicos
- Compostos heterocíclicos, 1 anel
- Compostos heterocíclicos
- Compostos heterocíclicos, 2 anel
- Compostos heterocíclicos, anel fundido
- Hidrocarbonetos
- Cicloparaffinas
- Hidrocarbonetos, aliciclicos
- Hidrocarbonetos, cíclicos
- Terpenos
- Carboidratos
- Hidrocarbonetos aromáticos policíclicos
- Hidrocarbonetos, aromáticos
- Compostos policíclicos
- Glicosídeos
- Indoles
- Taxóides
- Ciclodecanos
- Diterpenos
- Desoxicitidina
- Citidina
- Nucleosídeos de pirimidina
- Pirimidinas
- Antraciclinas
- Nafthacenos
- Aminoglicosídeos
- Daunorubicina
- Quinonas
- Azirines
- Mitomicinas
- Indolequinonas
- Doxorrubicina
- Docetaxel
- Gemcitabina
- Mitomicina
- Epirrubicina
Outros números de identificação do estudo
- SZB-URO-26-001
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
After completion of the trial for the primary endpoint, deidentified data will be shared to other researches upon request.
Prazo de Compartilhamento de IPD
After completion of the trial to the primary endpoint.
Tipo de informação de suporte de compartilhamento de IPD
- PROTOCOLO DE ESTUDO
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