Study of Weekly Radiotherapy for Bladder Cancer

NCT ID: NCT01810757

Last Updated: 2026-01-15

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

65 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-04-30

Study Completion Date

2023-04-30

Brief Summary

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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:

1. whether treatment using adaptive planning can be successfully delivered at multiple sites across the UK and results in acceptable levels of toxicity
2. the local tumour control rate achieved by hypofractionated weekly radiotherapy
3. 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.

Detailed Description

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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

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Bladder Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Standard planning

Standard planning radiotherapy

Group Type ACTIVE_COMPARATOR

Standard planning radiotherapy

Intervention Type RADIATION

36 Gray dose given in 6 fractions of 6 Grays over 6 weeks, using one plan per patient.

Adaptive planning

Adaptive planning radiotherapy

Group Type EXPERIMENTAL

Adaptive planning radiotherapy

Intervention Type RADIATION

36 Gray dose given in 6 fractions of 6 Grays over 6 weeks, selecting the best fit from three plans per patient.

Interventions

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Standard planning radiotherapy

36 Gray dose given in 6 fractions of 6 Grays over 6 weeks, using one plan per patient.

Intervention Type RADIATION

Adaptive planning radiotherapy

36 Gray dose given in 6 fractions of 6 Grays over 6 weeks, selecting the best fit from three plans per patient.

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cancer Research UK

OTHER

Sponsor Role collaborator

Institute of Cancer Research, United Kingdom

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Robert Huddart

Role: PRINCIPAL_INVESTIGATOR

Institute of Cancer Research/RMNHSFT

Locations

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Addenbrooke's Hospital

Cambridge, , United Kingdom

Site Status

Velindre Cancer Centre

Cardiff, , United Kingdom

Site Status

Ipswich Hospital

Ipswich, , United Kingdom

Site Status

St James's University Hospital

Leeds, , United Kingdom

Site Status

Guy's & St Thomas's Hospital

London, , United Kingdom

Site Status

Royal Marsden NHSFT

London, , United Kingdom

Site Status

University College London

London, , United Kingdom

Site Status

Clatterbridge Cancer Centre

Metropolitan Borough of Wirral, , United Kingdom

Site Status

Norfolk & Norwich University Hospitals NHS Foundation Trust

Norwich, , United Kingdom

Site Status

Royal Preston Hospital

Preston, , United Kingdom

Site Status

Queens Hospital

Romford, , United Kingdom

Site Status

Countries

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United Kingdom

References

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Farbiszewski R, Ustymowicz J, Dudek H. [Participation of free radicals in the mechanism of brain tissue damage]. Neurol Neurochir Pol. 1993 Sep-Oct;27(5):729-37. Polish.

Reference Type RESULT
PMID: 8114997 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32461298 (View on PubMed)

Other Identifiers

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CRUK/12/055

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

ICR-CTSU/2013/10039

Identifier Type: OTHER

Identifier Source: secondary_id

CCR3973

Identifier Type: -

Identifier Source: org_study_id

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