Clinical trial NCT03348969: Neoadjuvant Short-term Intensive Chemoresection Versus Standard Adjuvant Intravesical Instillations in NMIBC
Official title: Neoadjuvant Short-term Intensive Chemoresection Versus Standard Adjuvant Intravesical Instillations in NMIBC
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Bladder Cancer
Keywords: Mitomycin C
Neoadjuvant
Lead sponsor: Aarhus University Hospital
Sponsor class: OTHER
First posted: 2017-11-21
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized Clinical Trial
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 2-year recurrence rate
timeFrame: within 2 years
Secondary outcomes:
measure: Tumour response rate
timeFrame: 6 months after complete enrollment
measure: 5-year recurrence rate
timeFrame: within 5 years
measure: Adverse events
timeFrame: 6 months after complete enrollment
measure: Biomarkers
timeFrame: within 2 years
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
Study officials:
affiliation: Aarhus University Hospital
name: Jørgen Bjerggaard Jensen, MD
role: PRINCIPAL_INVESTIGATOR
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