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

NCT06781879 | Recruiting Phase 4 DMC

• 1 other identifier: COBRA NMIBC
• Study Type: interventional
• Target: 272
• Locations: 4 countries
• Sites: 8

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

Keywords

Recurrence; Ta low.grade; Chemoablation

Outcome Measures

Primary Outcomes (1)

• Two-year Recurrence Free Survival

  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.

  2 years

Secondary Outcomes (8)

• Five-year RFS

  5 years

• Number of patients in need of a TURBT or tumour fulguration in the outpatient clinic in the first two years following randomisation

  2 years

• Number of tumours at first recurrence based on the following intervals: 1, 2-7, > 8

  5 years

• 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

• Five-year progression free survival

  5 years

Study Arms (2)

Chemoablation

EXPERIMENTAL

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 ).

Drug: Mitomycin c

Control

NO INTERVENTION

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.

Interventions

Mitomycin c DRUG

Chemoablation

Chemoablation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jakob Kristian Jakobsen: lead
• medac GmbH: collaborator
• Danish Cancer Society: collaborator

Study Sites (8)

Aalborg University Hospital

Aalborg, Denmark

NOT YET RECRUITING

Aarhus University Hospital

Aarhus N, 8200, Denmark

RECRUITING

Herlev and Gentofte Hospital

Herlev, Denmark

RECRUITING

Zealand University Hospital, Roskilde

Roskilde, Denmark

RECRUITING

Landspítali University Hospital

Reykjavik, Iceland

NOT YET RECRUITING

Haukeland University Hospital

Bergen, Norway

NOT YET RECRUITING

Vestfold Hospital Trust

Tønsberg, Norway

NOT YET RECRUITING

NU Hospital Group

Uddevalla, Sweden

NOT YET RECRUITING

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms; Recurrence

Interventions

Mitomycin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Pernille Kingo, PhD, Dr

CONTACT

0045 78 45 00 00; pernking@rm.dk

Vibeke Morrison, Rn, Msc Nurs

CONTACT

vimorr@rm.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior consultant and acting head of urological research unit

Model Details: international multicenter RCT

Study Record Dates

• First Submitted: January 14, 2025
• First Posted: January 17, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2032
• Last Updated: October 3, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1); DK (4); IC (1); NO (2)