High-Risk Non-Muscle Invasive Bladder CancerPhase 3TRAINNCT07268339
A Phase III Randomised Control Clinical Trial of Radiotherapy With Radiosensitisation Versus Intravesical Bacillus Calmette-Guerin Therapy for High-risk Non-muscle Invasive Bladder Cancer.
A Phase 3 study testing radiotherapy and BCG in people with High-Risk Non-Muscle Invasive Bladder Cancer, run by The Christie NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
In the UK 20,000 people develop urothelial bladder cancer each year with 75-80% having Non-Muscle Invasive Bladder Cancer (NMIBC). The current standard of care for patients with High Risk-NMIBC (HR-NMIBC) is either surgery to remove the tumour (transurethral resection of bladder tumour; TURBT) followed by BCG… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- High-Risk Non-Muscle Invasive Bladder Cancer
- What is being tested?
- radiotherapy and BCG
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 328 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Dec 2025to 1 Dec 2031
- Phase
- Phase 3
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosed with histologically confirmed grade 3 T1 N0 M0 transitional cell carcinoma, OR carcinoma in situ of the bladder (and N0 M0), OR both, with detrusor muscle present in the biopsy specimen if T1 disease (or a repeat resection that does contain muscle that is clear)
- Suitable for BCG treatment
- Suitable for radiotherapy and radiosensitisation according to the schedule of administration outlined in the Radiotherapy Planning Guidance document.
- Life expectancy over 12 months
- ECOG performance status 0 - 2
- Age >=16 years
- Provided written informed consent
Who cannot join
- MDT selected patients with HR-NMIBC who are deemed best suited for primary cystectomy (patients that have had this treatment recommendation but then decline cystectomy remain eligible for TRAIN)
- Previous radiotherapy to the pelvis
- Previous intravesical therapy
- Poor bladder function (IPSS >16)
- A recent or current other cancer. Current non-melanoma skin cancer, cervical carcinoma in situ or localized prostate cancer not requiring current treatment are permissible, as is a history of a separate other malignancy having completed all active treatment ≥2 years previously and without evidence of relapse
- Pre-existing medical conditions that preclude treatment options in either trial arm
Show all 9Show fewer
- Patient currently recruited to another interventional trial or participation within an interventional clinical trial within 3 months of the point of registration within TRAIN.
- Pregnant or breast-feeding
- Not able to use appropriate adequate effective contraception during and for 3 months after the study
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site
The Christie
Manchester, M20 4BX
Ananya Choudhury, Professor, 0845 226 3000, ananya.choudhury@nhs.net
About this study
Official title: TRAIN - A Phase III Randomised Control Clinical Trial of Radiotherapy With Radiosensitisation Versus Intravesical Bacillus Calmette-Guerin Therapy for High-risk Non-muscle Invasive Bladder Cancer.
In the UK 20,000 people develop urothelial bladder cancer each year with 75-80% having Non-Muscle Invasive Bladder Cancer (NMIBC). The current standard of care for patients with High Risk-NMIBC (HR-NMIBC) is either surgery to remove the tumour (transurethral resection of bladder tumour; TURBT) followed by BCG (Bacillus Calmette Guérin, an immunotherapy drug) given directly into the bladder, or surgery to remove the bladder (cystectomy). BCG is given weekly for six weeks followed by maintenance treatment up to 3 years. However, in up to 50% of patients their cancer returns (recurrence) or gets worse (progression) after BCG and 25% stop treatment due to side effects. Globally BCG supply has been restricted in recent years has increased HR-NMIBC recurrence rates and costs. Improved treatments are required, to prevent recurrence, progression and cystectomy, and mitigate the effects of unpredictable supply.
Trimodality treatment (TMT) is maximal TURBT + radiotherapy + a radiosensitiser (gemcitabine, mitomycin C/fluorouracil or carbogen/nicotinamide) and is an equivalent alternative treatment to cystectomy for muscle-invasive bladder cancer (MIBC). TMT is not routinely used for HR-NMIBC. A study found that 54% of HR-NMIBC patients who received TMT did not have recurrence within 5 years. Modern radiotherapy is expected to further improve outcomes and minimise side-effects.
Read more
Patients will be randomised 1:1 to BCG or radiotherapy with radiosensitisation. Patients randomised to the experimental arm will receive 55Gy in 20 fractions. Investigators can then choose from three different options for the radiosensitiser. TRAIN will test if radiotherapy with radiosensitisation improves outcomes for people with HR-NMIBC compared to BCG.
TRAIN will recruit 328 patients with HR-NMIBC following maximal TURBT. All patients will be followed up for a minimum of two years to record their response to treatment.
- Being tested
- radiotherapy, BCG
- Keywords
- non-muscle invasive bladder cancer, radiotherapy with radiosensitisation drugs, Bacillus Calmette-Guerin therapy
- Medical subject headings
- Non-Muscle Invasive Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
radiotherapyRadiation
Radiotherapy - 55Gy in 20 fractions treating once daily Monday to Friday over 4 weeks.
BCGOther
BCG protocol of 6 weekly intravesical instillations, followed by 3 weekly instillations at 3, 6, 12, 18, 24, 30, 36 months.
| Study group | Role | What they receive |
|---|---|---|
| Control Arm: BCG | Active comparator | This arm is standard of care for this patient group. A standard protocol of 6 weekly intravesical installations, followed by 3 weekly instillations at approximately 3, 6, 12, 18, 24, 30 months and 36 months (depending on toxicity). Stock is taken and given per local hospital guildlines. Receives: Other: BCG |
| Experimental Arm: Radiotherapy with Radiosentiser drugs. | Experimental | Patients randomised to the radiotherapy arm will receive a hypofractionated schedule of external beam radiotherapy with a regimen of 55Gy in 20 fractions given once daily Monday to Friday over 4 weeks. Radiotherapy will be delivered with a conventional or 3D conformal technique with an empty bladder. It will be administered concurrently with a radiosensitiser (detailed below) selected by the treating physician according to local institutional practice.
Radiosensitiser will be selected as one option from the following:
* Gemcitabine 75-100mg/m2 administered once a week during a four-week radiotherapy course. Cycle 1 will be given on the first radiotherapy day, to a planned total of 4 cycles. 2-4 hours prior to radiotherapy
* 5-FU and Mitomycin C - Fluorouracil 500mg/m2 Days 1-5 and 16-20 via continuous infusion. Mitomycin C 12mg/m2 Day 1 via intravenous infusion
* Carbogen and nicotinamide (CON) - 2% CO2 and 98% O2 Carbogen will be delivered through a closed breathing system with Receives: Radiation: radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare event-free survival between BCG and radiotherapy with radiosensitisation.
Event-free survival is defined as recurrence of CIS or high-risk non-muscle invasive papillary tumour, continued presence of HR NMIBC even after treatment completion, progression to muscle-invasive disease, distant metastatic bladder cancer, cystectomy (for any reason) or death from any cause.
Measured: From baseline to at least 96 weeks after initial of treatment.
Secondary outcomes (10)
To determine the difference between BCG and radiotherapy in terms of patient-reported symptoms.
Patient-reported outcomes will be assessed via questionnaires, including the RTOG (late bladder and intestinal toxicity) questionnaire.
Measured: From baseline to at least 96 weeks post treatment.
To evaluate each component of the primary outcome comparing between BCG and radiotherapy with radiosensitisation.
The following event outcomes will be analyzed using the Cox proportional hazards model to estimate hazard ratios, and Kaplan-Meier analysis will be used to estimate event rates.
- Recurrence-free survival (RFS) defined as time from randomisation to recurrence of non-muscle invasive papillary tumour. Patients are censored at the last follow-up if event free.
- Progression-free survival (PFS) defined as time from randomisation to progression to muscle-invasive disease. Patients are censored at the last follow-up if event free.
- Metastasis-free survival (MFS) defined as time from randomisation to progression to distant metastatic bladder cancer. Patients are censored at the last follow-up if event free.
- Cystectomy-free survival (CFS) defined as time from randomisation to cystectomy. Patients are censored at the last follow-up if event free
- Overall survival (OS) defined as time from randomisation to death due to any cause. Patients are censored at the last follow-up if event free
Measured: From baseline to at least 96 weeks post treatment.
To establish the tolerability and safety of radiotherapy.
MedDRA coded adverse events graded using CTCAE v5.0.
Measured: From baseline to at least end of 4 week treatment.
To determine the difference in cancer specific survival between groups.
Cancer specific survival defined as time from randomisation to death from cancer. Patients who die of a cause other than the cancer under study or who are lost to follow-up are censored at death or the last date on which they were known to be alive.
Measured: From baseline to at least 96 weeks post treatment.
To determine the difference in treatment fidelity between the groups.
Treatment fidelity defined as how well each group implemented treatment as intended. Summary statistics will be presented for any treatment delays, missed treatment, those not starting treatment, and those who completed treatment, by group.
Measured: From baseline to at least 96 weeks post treatment.
To determine the cost-effectiveness of radiotherapy with radiosensitisation compared to BCG.
- Within trial analysis. Total costs and QALYs for radiotherapy with radiosensitisation compared to BCG during the trial period.
- Economic modelling. Total costs and QALYs for radiotherapy with radiosensitisation compared to BCG extrapolated beyond the trial period.
Measured: From Baseline to at least 96 weeks post treatment.
To determine the difference between BCG and radiotherapy in terms of patient-reported symptoms.
Patient-reported outcomes will be assessed via questionnaires, including the EQ-5D questionnaire.
Measured: From baseline to at least 96 weeks post treatment.
To determine the difference between BCG and radiotherapy in terms of patient-reported symptoms.
Patient-reported outcomes will be assessed via questionnaires, including the IPSS questionnaire.
Measured: From baseline to at least 96 weeks post treatment.
To determine the difference between BCG and radiotherapy in terms of patient-reported symptoms.
Patient-reported outcomes will be assessed via questionnaires, including the QLQ-C30 questionnaire.
Measured: From baseline to at least 96 weeks post treatment.
To determine the difference between BCG and radiotherapy in terms of patient-reported symptoms.
Patient-reported outcomes will be assessed via questionnaires, including the QLQ-NMIBC24 questionnaire.
Measured: From baseline to at least 96 weeks post treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2025
- Study start1 Dec 2025 (estimated)
- Primary completion1 Dec 2031 (estimated)
- Study completion1 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High-Risk 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Model Description
- Masking
- None (open label)
- Enrolment
- 328 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Christie NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07268339
- Sponsor's protocol ID
- CFTsp223
- Acronym
- TRAIN
- Status last verified
- Nov 2025
- First submitted
- 24 Sep 2025
- Last updated
- 5 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data will be made available, including data dictionaries, for approved data-sharing requests. Individual participant data will be shared that underlie the results reported in this article, after de-identification and normalisation of information (text, tables, figures, and appendices). The study protocol and statistical analysis plan will also be available.
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TRAIN - A Phase III Randomised Control Clinical Trial of Radiotherapy With Radiosensitisation Versus Intravesical Bacillus Calmette-Guerin Therapy for High-risk Non-muscle Invasive Bladder Cancer.
- ClinicalTrials.gov ID
- NCT07268339
- Acronym / sponsor ID
- TRAIN / CFTsp223
- Keywords
- non-muscle invasive bladder cancer, radiotherapy with radiosensitisation drugs, Bacillus Calmette-Guerin therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 328 participants (estimated)
- Lead sponsor
- The Christie NHS Foundation TrustUniversity, hospital or other
- Study start
- 1 Dec 2025 (estimated)
- Primary completion
- 1 Dec 2031 (estimated)
- Study completion
- 1 Dec 2031 (estimated)
- First posted
- 5 Dec 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.
In the UK 20,000 people develop urothelial bladder cancer each year with 75-80% having Non-Muscle Invasive Bladder Cancer (NMIBC). The current standard of care for patients with High Risk-NMIBC (HR-NMIBC) is either surgery to remove the tumour (transurethral resection of bladder tumour; TURBT) followed by BCG (Bacillus Calmette Guérin, an immunotherapy drug) given directly into the bladder, or surgery to remove the bladder (cystectomy). BCG is given weekly for six weeks followed by maintenance treatment up to 3 years. However, in up to 50% of patients their cancer returns (recurrence) or gets worse (progression) after BCG and 25% stop treatment due to side effects. Globally BCG supply has been restricted in recent years has increased HR-NMIBC recurrence rates and costs. Improved treatments are required, to prevent recurrence, progression and cystectomy, and mitigate the effects of unpredictable supply.
Trimodality treatment (TMT) is maximal TURBT + radiotherapy + a radiosensitiser (gemcitabine, mitomycin C/fluorouracil or carbogen/nicotinamide) and is an equivalent alternative treatment to cystectomy for muscle-invasive bladder cancer (MIBC). TMT is not routinely used for HR-NMIBC. A study found that 54% of HR-NMIBC patients who received TMT did not have recurrence within 5 years. Modern radiotherapy is expected to further improve outcomes and minimise side-effects.
Patients will be randomised 1:1 to BCG or radiotherapy with radiosensitisation. Patients randomised to the experimental arm will receive 55Gy in 20 fractions. Investigators can then choose from three different options for the radiosensitiser. TRAIN will test if radiotherapy with radiosensitisation improves outcomes for people with HR-NMIBC compared to BCG.
TRAIN will recruit 328 patients with HR-NMIBC following maximal TURBT. All patients will be followed up for a minimum of two years to record their response to treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Model Description
| Arm | Type | Receives |
|---|---|---|
| Control Arm: BCG | Active comparator | Other: BCGThis arm is standard of care for this patient group. A standard protocol of 6 weekly intravesical installations, followed by 3 weekly instillations at approximately 3, 6, 12, 18, 24, 30 months and 36 months (depending on toxicity). Stock is taken and given per local hospital guildlines. |
| Experimental Arm: Radiotherapy with Radiosentiser drugs. | Experimental | Radiation: radiotherapyPatients randomised to the radiotherapy arm will receive a hypofractionated schedule of external beam radiotherapy with a regimen of 55Gy in 20 fractions given once daily Monday to Friday over 4 weeks. Radiotherapy will be delivered with a conventional or 3D conformal technique with an empty bladder. It will be administered concurrently with a radiosensitiser (detailed below) selected by the treating physician according to local institutional practice. Radiosensitiser will be selected as one option from the following: * Gemcitabine 75-100mg/m2 administered once a week during a four-week radiotherapy course. Cycle 1 will be given on the first radiotherapy day, to a planned total of 4 cycles. 2-4 hours prior to radiotherapy * 5-FU and Mitomycin C - Fluorouracil 500mg/m2 Days 1-5 and 16-20 via continuous infusion. Mitomycin C 12mg/m2 Day 1 via intravenous infusion * Carbogen and nicotinamide (CON) - 2% CO2 and 98% O2 Carbogen will be delivered through a closed breathing system with |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Diagnosed with histologically confirmed grade 3 T1 N0 M0 transitional cell carcinoma, OR carcinoma in situ of the bladder (and N0 M0), OR both, with detrusor muscle present in the biopsy specimen if T1 disease (or a repeat resection that does contain muscle that is clear)
- Suitable for BCG treatment
- Suitable for radiotherapy and radiosensitisation according to the schedule of administration outlined in the Radiotherapy Planning Guidance document.
- Life expectancy over 12 months
- ECOG performance status 0 - 2
Key exclusion criteria (9 listed)
- MDT selected patients with HR-NMIBC who are deemed best suited for primary cystectomy (patients that have had this treatment recommendation but then decline cystectomy remain eligible for TRAIN)
- Previous radiotherapy to the pelvis
- Previous intravesical therapy
- Poor bladder function (IPSS >16)
- A recent or current other cancer. Current non-melanoma skin cancer, cervical carcinoma in situ or localized prostate cancer not requiring current treatment are permissible, as is a history of a separate other malignancy having completed all active treatment ≥2 years previously and without evidence of relapse
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 |
|---|---|---|
| radiotherapyRadiotherapy - 55Gy in 20 fractions treating once daily Monday to Friday over 4 weeks. | Radiation | Experimental Arm: Radiotherapy with Radiosentiser drugs. |
| BCGBCG protocol of 6 weekly intravesical instillations, followed by 3 weekly instillations at 3, 6, 12, 18, 24, 30, 36 months. | Other | Control Arm: BCG |
Primary outcome
To compare event-free survival between BCG and radiotherapy with radiosensitisation.
Time frame: From baseline to at least 96 weeks after initial of treatment.
Event-free survival is defined as recurrence of CIS or high-risk non-muscle invasive papillary tumour, continued presence of HR NMIBC even after treatment completion, progression to muscle-invasive disease, distant metastatic bladder cancer, cystectomy (for any reason) or death from any cause.
10 secondary outcomes
To determine the difference between BCG and radiotherapy in terms of patient-reported symptoms.
Time frame: From baseline to at least 96 weeks post treatment.
To evaluate each component of the primary outcome comparing between BCG and radiotherapy with radiosensitisation.
Time frame: From baseline to at least 96 weeks post treatment.
To establish the tolerability and safety of radiotherapy.
Time frame: From baseline to at least end of 4 week treatment.
To determine the difference in cancer specific survival between groups.
Time frame: From baseline to at least 96 weeks post treatment.
To determine the difference in treatment fidelity between the groups.
Time frame: From baseline to at least 96 weeks post treatment.
To determine the cost-effectiveness of radiotherapy with radiosensitisation compared to BCG.
Time frame: From Baseline to at least 96 weeks post treatment.
To determine the difference between BCG and radiotherapy in terms of patient-reported symptoms.
Time frame: From baseline to at least 96 weeks post treatment.
To determine the difference between BCG and radiotherapy in terms of patient-reported symptoms.
Time frame: From baseline to at least 96 weeks post treatment.
To determine the difference between BCG and radiotherapy in terms of patient-reported symptoms.
Time frame: From baseline to at least 96 weeks post treatment.
To determine the difference between BCG and radiotherapy in terms of patient-reported symptoms.
Time frame: From baseline to at least 96 weeks post treatment.
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 5 Dec 2025.
- The TRAIN trial website.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Individual participant data will be made available, including data dictionaries, for approved data-sharing requests. Individual participant data will be shared that underlie the results reported in this article, after de-identification and normalisation of information (text, tables, figures, and appendices). The study protocol and statistical analysis plan will also be available.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing radiotherapy and BCG in people with High-Risk Non-Muscle Invasive Bladder Cancer, run by The Christie NHS Foundation Trust at 1 site in United Kingdom.
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 7 inclusion and 9 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: opening soon, as of the sponsor's last update on 5 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Amber B Cole (023 8120 5154, train@soton.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To compare event-free survival between BCG and radiotherapy with radiosensitisation. (time frame: From baseline to at least 96 weeks after initial of treatment.). 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 5 Dec 2025.