Chemoablation Or Bladder Resection With Adjuvant Chemotherapy in Recurrent Non-Muscle Invasive Bladder Cancer

NCT ID: NCT06781879

Last Updated: 2025-10-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 272 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-01
• Study Completion Date: 2032-02-01

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

Conditions

Non-Muscle Invasive Bladder Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chemoablation

Patients will undergo dose dense chemoablation with MMC three times per week for two weeks (six instillations in total) followed by flexible cystoscopy eight weeks later. If no tumour can be identified (complete response), patients will receive monthly MMC maintenance instillations for 6 months (six instillations in total) and then continue in the outpatient follow-up programme, according to European guidelines. If tumour regression is observed without complete response or there is no response, a TURBT or outpatient biopsy and tumour fulguration will be performed followed by adjuvant BCG with induction therapy and 1 year maintenance (6 weekly instillations as induction followed by 3 weekly instillations as maintenance at 3, 6, and 12 months or 4, 8 and 12 months as is standard for site ).

Group Type: EXPERIMENTAL

Mitomycin c

Intervention Type: DRUG

Chemoablation

Control

Patients will have TURBT or outpatient biopsy and tumour fulguration performed, followed by standard intravesical instillation therapy according to tumour histology: MMC once a week for six weeks with a monthly maintenance instillation for six months in low-grade tumours. For high-grade tumours BCG will be utilised once a week for six weeks followed by 1-year maintenance consisting of one weekly instillation for three weeks after 3, 6, and 12 months or 4, 8 and 12 months as is standard for site.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Mitomycin c

Chemoablation

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

medac GmbH

INDUSTRY

Sponsor Role: collaborator

Danish Cancer Society

OTHER

Sponsor Role: collaborator

Jakob Kristian Jakobsen

OTHER

Sponsor Role: lead

Responsible Party

Jakob Kristian Jakobsen

Senior consultant and acting head of urological research unit

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Aalborg University Hospital

Aalborg, , Denmark

Site Status: NOT_YET_RECRUITING

Aarhus University Hospital

Aarhus N, , Denmark

Site Status: RECRUITING

Herlev and Gentofte Hospital

Herlev, , Denmark

Site Status: RECRUITING

Zealand University Hospital, Roskilde

Roskilde, , Denmark

Site Status: RECRUITING

Landspítali University Hospital

Reykjavik, , Iceland

Site Status: NOT_YET_RECRUITING

Haukeland University Hospital

Bergen, , Norway

Site Status: NOT_YET_RECRUITING

Vestfold Hospital Trust

Tønsberg, , Norway

Site Status: NOT_YET_RECRUITING

NU Hospital Group

Uddevalla, , Sweden

Site Status: NOT_YET_RECRUITING

Countries

Denmark; Iceland; Norway; Sweden

Central Contacts

Pernille Kingo, PhD, Dr

Role: CONTACT

pernking@rm.dk

0045 78 45 00 00

Vibeke Morrison, Rn, Msc Nurs

Role: CONTACT

vimorr@rm.dk

Facility Contacts

Knud Fabrin, MD

Role: primary

knf@rn.dk

Pernille Skjold Kingo Assosiate prof., Senior consultant, PhD

Role: primary

perkin@rm.dk

+45 30915600

Ann K Bersang, MD

Role: primary

ann.kortbaek.bersang@regionh.dk

Juan L Vásquez, PhD

Role: primary

Julv@regionsjaelland.dk

Sigurður Guðjónsson, PhD

Role: primary

sigugud@landspitali.is

Gigja Gudbrandsdottir, PhD

Role: primary

gigja.gudbrandsdottir@helse-bergen.no

Erik S Haug, MD

Role: primary

Erik.haug@siv.no

Suleiman Abuhasanein, MD

Role: primary

suleiman.abuhasanein@vgregion.se

Other Identifiers

COBRA NMIBC

Identifier Type: -

Identifier Source: org_study_id