Non-Muscle Invasive Bladder Cancer
Conditions
Keywords
Recurrence, Ta low.grade, Chemoablation
Brief summary
The investigartors will conduct a randomized, multinational study with the aim to assess if the efficacy of a dose dense chemoablation with Mitomycin C (MMC) with adjuvant BCG in non-responding patients is superior regarding long term effect compared to standard treatment with trans urethral resection of bladder tumors (TURBT) and adjuvant intravesical instillation therapy in patients with recurrent Ta LG tumors. The study is a natural follow-up study following the pivotal NICSA trial supported by the Danish Cancer Society that has lead to the initial change in the European guidelines. In order to not only be comparable to current standard, but also to improve clinical outcome and furthermore confirm the previous findings, the investigators here suggest to implement at patient tailored approach through a new multicenter RCT. The investigators hypothesize that chemoablation with MMC in patients with recurrent Ta LG tumors will result in a permanent low recurrence rate in patients with complete response, whereas patients without complete response can be selected for adjuvant BCG which theoretically is more efficient in this select patient group. This will potentially result in a more favorable long term recurrence free survival (RFS) rate compared to the current standard regimen where all patients are treated with TURBT and adjuvant instillation therapy. The incidence of bladder cancer in Denmark is almost 2,000 per year. Of these, 75% have non-muscle invasive bladder cancer (NMIBC). The yearly recurrence rate of NMIBC is approximately 35% and the disease is therefore one of the most costly cancers to manage on a per patient basis, due to the cost of operative procedures, follow-up cystoscopies and instillation therapies
Interventions
DRUGMitomycin c
Chemoablation
Sponsors
medac GmbH
Danish Cancer Society
Jakob Kristian Jakobsen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
international multicenter RCT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Tumour recurrence after previous urothelial tumour of Ta low-grade * Tumours smaller than 2 cm in diameter * Negative urine cytology (optional) * ≥18 years of age * Ability to understand and comprehend the provided written and oral information * Has provided written consent
Exclusion criteria
* Known history of invasive tumour of the bladder (T1+) * Known history of CIS of the bladder * Previous MMC or BCG-treatment except for single instillations following previous TURBTs * Known allergy or intolerance to MMC * Solid tumour with suspicions of invasion * Tumour in the bladder neck or urethra * Suspicion of CIS (positive cytology with high-grade neoplastic cells combined with suspicious flat lesions seen at cystoscopy) * Small bladder volume (less than 100 ml) or incontinence * Prior radiation therapy to the pelvic area, as radiation affects the bladder function and instillation therapy is a suboptimal treatment for this patient group * Acute cystitis * Pregnancy or breast-feeding * Averse to using secure contraception with regard to men with partners and premenopausal women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Two-year Recurrence Free Survival | 2 years | This is defined as event of first recurrence following treatment but not including the recurrence diagnosed at the time of inclusion or persisting tumour following chemoablation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients in need of a TURBT or tumour fulguration in the outpatient clinic in the first two years following randomisation | 2 years | need for TURBT/fulgaration |
| Number of tumours at first recurrence based on the following intervals: 1, 2-7, > 8 | 5 years | tumour number |
| Number of TURBTs per patient in the first two and five years of follow-up based on the following intervals: 1, 2-5, 5-10 and multiple | 5 years | number of TURBTs |
| Five-year RFS | 5 years | This is defined as event of first recurrence following treatment but not including the recurrence diagnosed at the time of inclusion or persisting tumour following chemoablation. |
| Five-year overall survival | 5 years | survival |
| Number of patients completing assigned intervention | 2 years | completing assigned intervention |
| Serious adverse events related to MMC treatment during neoadjuvant or adjuvant therapy | 2 years | SAE's |
| Five-year progression free survival | 5 years | (progression defined as progression to T1-tumour, T2+-tumour, or cystectomy irrespectively of indication) |
Countries
Denmark, Iceland, Norway, Sweden
Contacts
Primary ContactPernille Kingo, PhD, Dr
Backup ContactVibeke Morrison, Rn, Msc Nurs
Outcome results
None listed