Neoadjuvant Short-term Intensive Chemoresection Versus Standard Adjuvant Intravesical Instillations in NMIBC

Study Overview
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Brief Summary
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A randomized controlled trial aiming to investigate neoadjuvant, short-term intensive chemoresection with Mitomycin C compared to standard treatment with TURB and adjuvant intravesical instillation therapy in patients with recurrent non-muscle invasive bladder cancer (NMIBC).

Detailed Description
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Background: Bladder cancer is the 11th most common cancer in the world and one of the most costly cancers on a per patient basis, due to the cost of operative procedures, follow-up cystoscopies and instillation therapy. Furthermore there is a risk of progression to invasive and hence deadly cancer why efficient and immediate treatment is crucial. Treatment today consists of surgical removal of tumours (TURB) and adjuvant intravesical treatment. There is a chance; neoadjuvant intravesical treatment with chemotherapy can supersede surgical removal in chemo-sensitive tumours while however some tumours will not respond to intravesical chemotherapy. Currently it is not possible to predict which tumours are chemo-sensitive and which are not. Objectives: To assess the efficacy of neoadjuvant, short-term intensive chemoresection with Mitomycin C compared to standard treatment with TURB and adjuvant intravesical instillation therapy in patients with recurrent non-muscle invasive bladder cancer (NMIBC). To investigate the ability to predict chemo-response in patients with recurrent non-muscle invasive bladder cancer (NMIBC). Methods: A randomised clinical controlled trial will include 120 patients with recurrent NMIBC. The control group of 60 patients will receive standard care with TURB and adjuvant intravesical treatment. The intervention group of 60 patients will be submitted to neoadjuvant short-term intensive chemoresection with three instillations with Mitomycin C per week for two weeks. Remnant tumour tissue will be evaluated by flexible cystoscopy after four weeks. To investigate the ability to predict chemo-response in patients with recurrent NMIBC, a connection between biomarkers of the initial tumour tissue and tumour response will be assessed. Samples of the latest resected tumour prior to inclusion will be collected from all participants treated with neoadjuvant chemoresection and assessed against the tumour response seen in the trial. Perspectives: Validation of biomarkers to predict chemo-response will be an important step to integrate biomarkers in daily clinical practice and to individualize the treatment of NMIBC. In some cases surgery could be avoided while ineffective chemotherapy could be avoided in others.

Official Title
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Neoadjuvant Short-term Intensive Chemoresection Versus Standard Adjuvant Intravesical Instillations in NMIBC

Conditions
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Bladder Cancer

Intervention / Treatment
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* Drug: Mitomycin c


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Known history of urothelial non-invasive Ta-tumour low-grade or high-grade. ≥18 years old Mentally healthy individual The ability to understand Danish orally and in writing Exclusion Criteria: Known history of invasive tumour of the bladder (T1+) Known history of CIS of the bladder Previous BCG-treatment within the last 24 months Previous Mitomycin C-treatment (except single-shot postoperative instillation) Known allergy or intolerance to Mitomycin C Solid tumour with suspicions of invasion Single tumour of more than 2 cm in diameter Suspicion of CIS (positive cytology with high-grade neoplastic cells combined with suspicious cystoscopy for flat lesions). Small bladder volume (less than 100 ml) or incontinence Acute cystitis Pregnancy or breast-feeding Not willing to use secure contraception with regard to men with partners and premenopausal women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized Clinical Trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Neoadjuvant Mitomycin C | Drug: Mitomycin c<br>* Neoadjuvant Mitomycin C<br>* Other names: Mitomycin Medac;|
| Active Comparator: Control<br>Adjuvant Mitomycin C | Drug: Mitomycin c<br>* Neoadjuvant Mitomycin C<br>* Other names: Mitomycin Medac;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year recurrence rate | The primary outcome is the number of patients in need for a TURB or tumour fulguration in the first 2 years following randomization. TURBs included as primary endpoint are the initial TURB in the control group, the prospective TURB in the intervention group for patients without complete chemoresection as well as TURB due to recurrence in both study groups. In case a TURB is recommended, but a subject refuses to undergo surgery, the recommended TURB is also registered. | within 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumour response rate | Number of patients with complete, partial and incomplete tumour response on neoadjuvant, short-term intensive chemoresection with Mitomycin C. | 6 months after complete enrollment | 
| 5-year recurrence rate | The number of patients in need of a TURB or tumour fulguration in the outpatient clinic in the first 5 years following randomization. TURBs included are the initial TURB in the control group, the prospective TURB in the intervention group for patients without complete chemoresection as well as TURB due to recurrence in both study groups. In case a TURB is recommended, but a subject refuses to undergo surgery, the recommended TURB is also registered. | within 5 years | 
| Adverse events | Proportion of patients with adverse events related to neoadjuvant, short-term intensive chemoresection | 6 months after complete enrollment | 
| Biomarkers | Composition of 650 cancer-associated genes expressed on the last resected tumour | within 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mitomycin C, Neoadjuvant