Bladder CancerHYBRIDNCT01810757

Study of Weekly Radiotherapy for Bladder Cancer

A study testing Standard planning radiotherapy and Adaptive planning radiotherapy in people with Bladder Cancer, run by Institute of Cancer Research, United Kingdom at 11 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Bladder Cancer
What is being tested?: Standard planning radiotherapy and Adaptive planning radiotherapy
Type of treatment: Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 65 participants
Where: 11 sitesUnited Kingdom
Study dates: Apr 2014to Apr 2023
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

Written informed consent
Age ≥18 years
Histologically confirmed invasive bladder carcinoma (T2-T4a N0 M0; any histological sub-type)
Unsuitable for radical cystectomy or daily fractionated radiotherapy for any reason (including performance status, co-morbidity, patient refusal)
Expected survival >6 months
WHO performance status 0-3
Willing to undergo post treatment cystoscopy

Who cannot join

Nodal or metastatic disease
Concurrent malignancy
Previous pelvic radiotherapy
Urinary catheter in-situ
Any other contra-indication to radiotherapy (e.g. inflammatory bowel disease)
Unable to attend for post treatment follow up

Trial locations and contacts

11 sites in 1 country.

City, postcode or hospital

11 sites in 1 country

United Kingdom11 sites

Addenbrooke's Hospital
Cambridge
Velindre Cancer Centre
Cardiff
Ipswich Hospital
Ipswich
St James's University Hospital
Leeds
Guy's & St Thomas's Hospital
London
Royal Marsden NHSFT
London
University College London
London
Clatterbridge Cancer Centre
Metropolitan Borough of Wirral
Norfolk & Norwich University Hospitals NHS Foundation Trust
Norwich
Royal Preston Hospital
Preston
Queens Hospital
Romford

Other trials in United Kingdom

About this study

Official title: A Multicentre Randomised Phase II Study of HYpofractionated Bladder Radiotherapy With or Without Image Guided aDaptive Planning

Background Localised muscle invasive bladder cancer (MIBC) is life-threatening and can cause significant symptoms. Around 50% of patients with MIBC who are referred for radiotherapy are unfit for standard radical treatment (surgery or daily radiotherapy with chemotherapy), but would have a normal life expectancy if their cancer were adequately controlled. Retrospective studies suggest that radiotherapy which is given weekly using fewer fractions and higher doses (hypofractionated), may be an alternative where daily radiotherapy is not an option.

Radiotherapy treatment is planned based on information from a CT scan which shows the position and shape of the bladder. This plan needs to take into account the fact that the bladder's shape and position can change, depending on how full it is and because of where it is in relation to the bowel. A safety margin is therefore added around the bladder on the planned treatment, to reduce the risk of missing any of the bladder with the radiotherapy.

It is now possible to take scans of the bladder's position before each treatment and adjust the position of the treatment plan accordingly to ensure the bladder is fully covered by it. In this study we are also looking at whether it is possible to design a series of treatment plans with different size safety margins and then choose one that fits best for each particular day. This is called 'adaptive radiotherapy'. This technique may enable accurate treatment delivery using smaller safety margins and this might help to reduce side effects.

Aims

In patients with MIBC not suitable for cystectomy or daily radiotherapy we aim to assess:

whether treatment using adaptive planning can be successfully delivered at multiple sites across the UK and results in acceptable levels of toxicity
the local tumour control rate achieved by hypofractionated weekly radiotherapy
the requirement to treat with adaptive planning.

How results will be used Results will provide robust evidence for use of hypofractionated radiotherapy and assess whether this is a plausible and worthwhile treatment in this patient population. The randomised element of the trial will support the implementation of image-guided adaptive radiotherapy for bladder cancer in the UK. HYBRID will provide evidence on the benefits or otherwise of this methodology and inform the development of further trials in this and other patient groups.

Read the detailed description

OBJECTIVES:

Primary To assess whether adaptive radiotherapy techniques when delivered at multiple centres can lead to a reduction in the level of acute non-genitourinary (GU) toxicity experienced by patients with muscle invasive bladder cancer unsuitable for daily radical radiotherapy.

Secondary

Establish the local disease control rates of hypofractionated bladder radiotherapy as measured at 3 months
Assess time to local disease progression
Assess the overall survival time of patients who have received hypofractionated radiotherapy.
Investigate the control rate of presenting symptoms, the effect of hypofractionated treatment on late radiotherapy side effects and patient reported outcomes.
To establish the proportion of fractions benefiting from adaptive planning.

OUTLINE: This is a multicentre randomised Phase II study in patients with muscle invasive bladder who are not suitable for cystectomy or daily radiotherapy.

All patients will be planned to receive six 6Gray (Gy) fractions of image guided radiotherapy delivered weekly (total dose: 36Gy) and will be randomised to standard or adaptive planning.

Participants allocated to the standard planning group will have one radiotherapy plan generated and this will be used to deliver all 6 treatments, with a cone beam CT scan prior to treatment delivery which can be used by the local investigator to adjust treatment delivery according to local practice.

Participants allocated to adaptive planning will have three radiotherapy plans generated; small, medium and large. A cone beam CT taken prior to each treatment delivery will be used to select the most appropriate plan of the day.

Patients are followed up in terms of the trial up to 24 months, after this time only basic routine follow-up data will be collected.

PROJECTED ACCURAL: The aim is to recruit 62 participants, 31 to each treatment allocation.

Conditions: Bladder Cancer
Being tested: Standard planning radiotherapy, Adaptive planning radiotherapy
Medical subject headings: Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Standard planning radiotherapyRadiation
36 Gray dose given in 6 fractions of 6 Grays over 6 weeks, using one plan per patient.
Adaptive planning radiotherapyRadiation
36 Gray dose given in 6 fractions of 6 Grays over 6 weeks, selecting the best fit from three plans per patient.

Study groups in NCT01810757
Study group	Role	What they receive
Standard planning	Active comparator	Standard planning radiotherapy Receives: Radiation: Standard planning radiotherapy
Adaptive planning	Experimental	Adaptive planning radiotherapy Receives: Radiation: Adaptive planning radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

Proportion of Patients Experiencing Severe Acute Non-genitourinary Side Effects Following Radiotherapy.
Non-GU CTCAE G3+ treatment-related toxicity occurring within the first 3 months of radiotherapy completing
Measured: 12 weeks from completion of radiotherapy

Secondary outcomes (5)

Local Disease Control Rate
Presence of cancer in the bladder 3 months after treatment. Presented as the proportion of all patients regardless of treatment allocation (standard and adaptive combined) having evidence of residual tumour.
Measured: 3 months
Time to Local Disease Progression
From randomisation to a maximum follow-up of 30 months. It was pre-planned in the SAP to combine the two treatment arms together because there is insufficient statistical power to detect clinically meaningful differences.
Measured: Event-free survival estimates at 12 months and 24 months are reported.
Overall Survival
From randomisation to maximum follow-up of 56 months. It was pre-planned in the SAP to combine the two treatment arms together because there is insufficient statistical power to detect clinically meaningful differences.
Measured: Event-free survival estimates at 12 months and 24months are reported.
The Control Rate of Presenting Symptoms
Assessed by looking at change in symptom scores from pre to post radiotherapy. The number of patients with post-radiotherapy scores lower than their baseline score have been used to calculate the control rate of presenting symptoms and is presented separately for the two randomisation groups.
Measured: 3 months from the completion of radiotherapy
The Proportion of Fractions Benefiting From Adaptive Planning
Assessed by the number of small or large plans being selected rather than the medium plan for patients in the adaptive planning group. The denominator will be the total number of fractions received in the adaptive planning group.
Measured: End of treatment, treatment is given over 6 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2014Apr 2023

First posted14 Mar 2013 (estimated)
Study startApr 2014
Primary completionAug 2016
Study completionApr 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Bladder CancerStudies of the same condition, open and under way.
More trials run by Institute of Cancer Research, United KingdomThe sponsor's other registered studies.
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 N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 65 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01810757
Sponsor's protocol ID: CCR3973
Other IDs: CRUK/12/055, ICR-CTSU/2013/10039
Acronym: HYBRID
Status last verified: Dec 2025
First submitted: 8 Mar 2013
Last updated: 15 Jan 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Huddart R, Hafeez S, Lewis R, McNair H, Syndikus I, Henry A, Staffurth J, Dewan M, Vassallo-Bonner C, Moinuddin SA, Birtle A, Horan G, Rimmer Y, Venkitaraman R, Khoo V, Mitra A, Hughes S, Gibbs S, Kapur G, Baker A, Hansen VN, Patel E, Hall E; HYBRID Investigators. Clinical Outcomes of a Randomized Trial of Adaptive Plan-of-the-Day Treatment in Patients Receiving Ultra-hypofractionated Weekly Radiation Therapy for Bladder Cancer. Int J Radiat Oncol Biol Phys. 2021 Jun 1;110(2):412-424. doi: 10.1016/j.ijrobp.2020.11.068. Epub 2020 Dec 11.
PubMed 33316362
Hafeez S, Patel E, Webster A, Warren-Oseni K, Hansen V, McNair H, Miles E, Lewis R, Hall E, Huddart R. Protocol for hypofractionated adaptive radiotherapy to the bladder within a multicentre phase II randomised trial: radiotherapy planning and delivery guidance. BMJ Open. 2020 May 26;10(5):e037134. doi: 10.1136/bmjopen-2020-037134.
PubMed 32461298

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 2/3
Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study
Muscle Invasive Bladder Urothelial Carcinoma, Muscle Invasive Renal Pelvis Urothelial Carcinoma
RecruitingPhase 3
A Clinical Trial of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) and Pembrolizumab (MK-3475A) in Participants With Bladder Cancer (MK-2870-055)
Bladder Cancer
Active, not recruitingPhase 2/3
A Study of CTX-009 in Combination With Paclitaxel in Adult Patients With Unresectable Advanced, Metastatic or Recurrent Biliary Tract Cancers (COMPANION-002)
Biliary Tract Cancer, Cholangiocarcinoma
Recruiting
Effect of Cyclic Sighing Breathing Exercise on CRBD, Pain, and Sleep Quality in Patients Undergoing TUR
Transurethral Resection of Bladder Tumor, Transurethral Resection of the Prostate (TURP)
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma

All Bladder Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicentre Randomised Phase II Study of HYpofractionated Bladder Radiotherapy With or Without Image Guided aDaptive Planning
ClinicalTrials.gov ID: NCT01810757
Acronym / sponsor ID: HYBRID / CCR3973
Conditions: Bladder Cancer
Study type: Interventional
Recruitment status: Completed
Enrolment: 65 participants (actual)
Lead sponsor: Institute of Cancer Research, United KingdomUniversity, hospital or other
Collaborators: Cancer Research UK
Study start: Apr 2014 (actual)
Primary completion: Aug 2016 (actual)
Study completion: Apr 2023 (actual)
First posted: 14 Mar 2013 (estimated)
Results: Posted 15 Jan 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Aims

In patients with MIBC not suitable for cystectomy or daily radiotherapy we aim to assess:

whether treatment using adaptive planning can be successfully delivered at multiple sites across the UK and results in acceptable levels of toxicity
the local tumour control rate achieved by hypofractionated weekly radiotherapy
the requirement to treat with adaptive planning.

Detailed description

OBJECTIVES:

Secondary

Establish the local disease control rates of hypofractionated bladder radiotherapy as measured at 3 months
Assess time to local disease progression
Assess the overall survival time of patients who have received hypofractionated radiotherapy.
Investigate the control rate of presenting symptoms, the effect of hypofractionated treatment on late radiotherapy side effects and patient reported outcomes.
To establish the proportion of fractions benefiting from adaptive planning.

OUTLINE: This is a multicentre randomised Phase II study in patients with muscle invasive bladder who are not suitable for cystectomy or daily radiotherapy.

All patients will be planned to receive six 6Gray (Gy) fractions of image guided radiotherapy delivered weekly (total dose: 36Gy) and will be randomised to standard or adaptive planning.

Patients are followed up in terms of the trial up to 24 months, after this time only basic routine follow-up data will be collected.

PROJECTED ACCURAL: The aim is to recruit 62 participants, 31 to each treatment allocation.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Standard planning	Active comparator	Radiation: Standard planning radiotherapyStandard planning radiotherapy
Adaptive planning	Experimental	Radiation: Adaptive planning radiotherapyAdaptive planning radiotherapy

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Written informed consent
Age ≥18 years
Histologically confirmed invasive bladder carcinoma (T2-T4a N0 M0; any histological sub-type)
Unsuitable for radical cystectomy or daily fractionated radiotherapy for any reason (including performance status, co-morbidity, patient refusal)
Expected survival >6 months

Key exclusion criteria (6 listed)

Nodal or metastatic disease
Concurrent malignancy
Previous pelvic radiotherapy
Urinary catheter in-situ
Any other contra-indication to radiotherapy (e.g. inflammatory bowel disease)

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
Standard planning radiotherapy36 Gray dose given in 6 fractions of 6 Grays over 6 weeks, using one plan per patient.	Radiation	Standard planning
Adaptive planning radiotherapy36 Gray dose given in 6 fractions of 6 Grays over 6 weeks, selecting the best fit from three plans per patient.	Radiation	Adaptive planning

Primary outcome

Proportion of Patients Experiencing Severe Acute Non-genitourinary Side Effects Following Radiotherapy.
Time frame: 12 weeks from completion of radiotherapy
Non-GU CTCAE G3+ treatment-related toxicity occurring within the first 3 months of radiotherapy completing

5 secondary outcomes

Local Disease Control Rate
Time frame: 3 months
Time to Local Disease Progression
Time frame: Event-free survival estimates at 12 months and 24 months are reported.
Overall Survival
Time frame: Event-free survival estimates at 12 months and 24months are reported.
The Control Rate of Presenting Symptoms
Time frame: 3 months from the completion of radiotherapy
The Proportion of Fractions Benefiting From Adaptive Planning
Time frame: End of treatment, treatment is given over 6 weeks

Results and safety

Results posted to the registry on 15 Jan 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Standard Planning	32	32
Adaptive Planning	33	33

Primary outcome: Proportion of Patients Experiencing Severe Acute Non-genitourinary Side Effects Following Radiotherapy.

Time frame: 12 weeks from completion of radiotherapy. Count of participants. Unit: Participants

Measure	Standard Planning n = 30	Adaptive Planning n = 33
Value	4	2

Population analysed: Evaluable patient population: This population contains all randomised patients who have received at least one fraction of radiotherapy and are evaluable for the primary endpoint of acute toxicity (i.e. toxicity reported up to 3 months post radiotherapy). Patients had been reviewed for evaluability by the independent Trial steering committee (TSC) blinded to planning method and the TSC's view on evaluability for the primary endpoint has been used to define the evaluable patient population.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse event data was collected up to 24 months.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Standard Planning	11 of 32 (34.4%)	32 of 32 (100%)	Not reported
Adaptive Planning	9 of 33 (27.3%)	33 of 33 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 33316362Huddart R, Hafeez S, Lewis R, McNair H, Syndikus I, Henry A, Staffurth J, Dewan M, Vassallo-Bonner C, Moinuddin SA, Birtle A, Horan G, Rimmer Y, Venkitaraman R, Khoo V, Mitra A, Hughes S, Gibbs S, Kapur G, Baker A, Hansen VN, Patel E, Hall E; HYBRID Investigators. Clinical Outcomes of a Randomized Trial of Adaptive Plan-of-the-Day Treatment in Patients Receiving Ultra-hypofractionated Weekly Radiation Therapy for Bladder Cancer. Int J Radiat Oncol Biol Phys. 2021 Jun 1;110(2):412-424. doi: 10.1016/j.ijrobp.2020.11.068. Epub 2020 Dec 11.
Derived from this study: PubMed 32461298Hafeez S, Patel E, Webster A, Warren-Oseni K, Hansen V, McNair H, Miles E, Lewis R, Hall E, Huddart R. Protocol for hypofractionated adaptive radiotherapy to the bladder within a multicentre phase II randomised trial: radiotherapy planning and delivery guidance. BMJ Open. 2020 May 26;10(5):e037134. doi: 10.1136/bmjopen-2020-037134.

Related trials for Bladder Cancer

RecruitingPhase 2/3
Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study
Muscle Invasive Bladder Urothelial Carcinoma, Muscle Invasive Renal Pelvis Urothelial Carcinoma
RecruitingPhase 3
A Clinical Trial of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) and Pembrolizumab (MK-3475A) in Participants With Bladder Cancer (MK-2870-055)
Bladder Cancer
Active, not recruitingPhase 2/3
A Study of CTX-009 in Combination With Paclitaxel in Adult Patients With Unresectable Advanced, Metastatic or Recurrent Biliary Tract Cancers (COMPANION-002)
Biliary Tract Cancer, Cholangiocarcinoma
Recruiting
Effect of Cyclic Sighing Breathing Exercise on CRBD, Pain, and Sleep Quality in Patients Undergoing TUR
Transurethral Resection of Bladder Tumor, Transurethral Resection of the Prostate (TURP)
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma

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. This study is not recruiting at the moment.

Robert Huddart principal investigator

Institute of Cancer Research/RMNHSFT

11 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Standard planning radiotherapy and Adaptive planning radiotherapy in people with Bladder Cancer, run by Institute of Cancer Research, United Kingdom at 11 sites 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 6 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: finished, as of the sponsor's last update on 15 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites 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.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Patients Experiencing Severe Acute Non-genitourinary Side Effects Following Radiotherapy. (time frame: 12 weeks from completion of radiotherapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01810757, which also lists 2 linked publications.

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 15 Jan 2026.