Non-Muscle Invasive Bladder CancerPhase 4COBRA-NMIBCNCT06781879
Chemoablation Or Bladder Resection With Adjuvant Chemotherapy in Recurrent Non-Muscle Invasive Bladder Cancer
A Phase 4 study testing Mitomycin c in people with Non-Muscle Invasive Bladder Cancer, run by Jakob Kristian Jakobsen at 8 sites in 4 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Muscle Invasive Bladder Cancer
- What is being tested?
- Mitomycin c
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 272 participants
- Where
- 8 sitesin 4 countries
- Study dates
- 1 Jun 2025to 1 Feb 2032
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
8 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
Vibeke Morrison, Rn, Msc Nurs contact
8 sites in 4 countries
Denmark4 sites, 4 recruiting
- Not yet recruiting
Aalborg University Hospital
Aalborg
Knud Fabrin, MD, knf@rn.dk
- Recruiting
Aarhus University Hospital
Aarhus N, 8200
Pernille Skjold Kingo Assosiate prof., Senior consultant, PhD, +45 30915600, perkin@rm.dk
- Recruiting
Herlev and Gentofte Hospital
Herlev
Ann K Bersang, MD, ann.kortbaek.bersang@regionh.dk
- Recruiting
Zealand University Hospital, Roskilde
Roskilde
Juan L Vásquez, PhD, Julv@regionsjaelland.dk
Norway2 sites, 2 recruiting
- Not yet recruiting
Haukeland University Hospital
Bergen
Gigja Gudbrandsdottir, PhD, gigja.gudbrandsdottir@helse-bergen.no
- Not yet recruiting
Vestfold Hospital Trust
Tønsberg
Erik S Haug, MD, Erik.haug@siv.no
Iceland1 site, 1 recruiting
- Not yet recruiting
Landspítali University Hospital
Reykjavik
Sigurður Guðjónsson, PhD, sigugud@landspitali.is
Sweden1 site, 1 recruiting
- Not yet recruiting
NU Hospital Group
Uddevalla
Suleiman Abuhasanein, MD, suleiman.abuhasanein@vgregion.se
About this study
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.
Read more
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
- Being tested
- Mitomycin c
- Keywords
- Recurrence, Ta low.grade, Chemoablation
- Medical subject headings
- Non-Muscle Invasive Bladder Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mitomycin cDrug
Chemoablation
| Study group | Role | What they receive |
|---|---|---|
| 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 ). Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years
Secondary outcomes (8)
Five-year RFS
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.
Measured: 5 years
Number of patients in need of a TURBT or tumour fulguration in the outpatient clinic in the first two years following randomisation
need for TURBT/fulgaration
Measured: 2 years
Number of tumours at first recurrence based on the following intervals: 1, 2-7, > 8
tumour number
Measured: 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
number of TURBTs
Measured: 5 years
Five-year progression free survival
(progression defined as progression to T1-tumour, T2+-tumour, or cystectomy irrespectively of indication)
Measured: 5 years
Five-year overall survival
survival
Measured: 5 years
Number of patients completing assigned intervention
completing assigned intervention
Measured: 2 years
Serious adverse events related to MMC treatment during neoadjuvant or adjuvant therapy
SAE's
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2025
- Study start1 Jun 2025
- Primary completion1 Feb 2029 (estimated)
- Study completion1 Feb 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Muscle Invasive Bladder CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- international multicenter RCT
- Masking
- None (open label)
- Enrolment
- 272 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jakob Kristian Jakobsen
- Sponsor type
- University, hospital or other
- Collaborators
- medac GmbH, Danish Cancer Society
- Responsible party
- Sponsor-investigator, Jakob Kristian Jakobsen, Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06781879
- Sponsor's protocol ID
- COBRA NMIBC
- Acronym
- COBRA-NMIBC
- Status last verified
- Sep 2025
- First submitted
- 14 Jan 2025
- Last updated
- 3 Oct 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chemoablation Or Bladder Resection With Adjuvant Chemotherapy in Recurrent Non-Muscle Invasive Bladder Cancer
- ClinicalTrials.gov ID
- NCT06781879
- Acronym / sponsor ID
- COBRA-NMIBC / COBRA NMIBC
- Conditions
- Non-Muscle Invasive Bladder Cancer
- Keywords
- Recurrence, Ta low.grade, Chemoablation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 272 participants (estimated)
- Lead sponsor
- Jakob Kristian JakobsenUniversity, hospital or other
- Collaborators
- medac GmbH, Danish Cancer Society
- Study start
- 1 Jun 2025 (actual)
- Primary completion
- 1 Feb 2029 (estimated)
- Study completion
- 1 Feb 2032 (estimated)
- First posted
- 17 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- international multicenter RCT
| Arm | Type | Receives |
|---|---|---|
| Chemoablation | Experimental | Drug: Mitomycin cPatients 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 ). |
| 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mitomycin cChemoablation | Drug | Chemoablation |
Primary outcome
Two-year Recurrence Free Survival
Time frame: 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.
8 secondary outcomes
Five-year RFS
Time frame: 5 years
Number of patients in need of a TURBT or tumour fulguration in the outpatient clinic in the first two years following randomisation
Time frame: 2 years
Number of tumours at first recurrence based on the following intervals: 1, 2-7, > 8
Time frame: 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
Time frame: 5 years
Five-year progression free survival
Time frame: 5 years
Five-year overall survival
Time frame: 5 years
Number of patients completing assigned intervention
Time frame: 2 years
Serious adverse events related to MMC treatment during neoadjuvant or adjuvant therapy
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2025.
- Individual participant dataSharing planned: No
Related trials for Non-Muscle Invasive Bladder Cancer
Not yet recruitingObservational study
Outcomes for IR and High Risk (HR) Non-muscle Invasive Bladder Cancer (NMIBC) and ctDNA-based Biomarkers for Response and Recurrence in Muscle Invasive Bladder Cancer (MIBC)
NMIBC, MIBC
Active, not recruitingPhase 2
Testing the Addition of an Anti-cancer Drug, Pembrolizumab, to the Usual Intravesical Chemotherapy Treatment (Gemcitabine) for the Treatment of BCG-Unresponsive Non-muscle Invasive Bladder Cancer
Bladder Flat Urothelial Carcinoma In Situ, Non-Muscle Invasive Bladder Urothelial Carcinoma
RecruitingPhase 2
A Phase II Trial of Bicalutamide in Patients Receiving Intravesical BCG for Non-muscle Invasive Bladder Cancer
Non-Muscle Invasive Bladder Cancer
Active, not recruitingPhase 3
Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Bacillus Calmette-Guerin (BCG) in High-Risk Non-Muscle Invasive Bladder Cancer (HR NMIBC) (MK-3475-676/KEYNOTE-676)
High-risk Non-muscle Invasive Bladder Cancer
Not yet recruitingPhase 2
Antibody-Drug Conjugate Plus Immunotherapy Versus Immunotherapy Plus Chemotherapy for Extensive Transurethrally Unresectable Very-High-Risk Non-Muscle-Invasive Bladder Cancer
Bladder (Urothelial, Transitional Cell) Cancer, Antibody-drug Conjugates
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Vibeke Morrison, Rn, Msc Nurs contact
8 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Mitomycin c in people with Non-Muscle Invasive Bladder Cancer, run by Jakob Kristian Jakobsen at 8 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Denmark, Norway, Iceland, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Pernille Kingo, PhD, Dr (0045 78 45 00 00, pernking@rm.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Two-year Recurrence Free Survival (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2025.