Study of Weekly Radiotherapy for Bladder Cancer

Study Overview
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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: 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.

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

Conditions
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Bladder Cancer

Intervention / Treatment
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* Radiation: Standard planning radiotherapy
* Radiation: Adaptive planning radiotherapy


Participation Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard planning<br>Standard planning radiotherapy | Radiation: Standard planning radiotherapy<br>* 36 Gray dose given in 6 fractions of 6 Grays over 6 weeks, using one plan per patient.<br>|
| Experimental: Adaptive planning<br>Adaptive planning radiotherapy | Radiation: Adaptive planning radiotherapy<br>* 36 Gray dose given in 6 fractions of 6 Grays over 6 weeks, selecting the best fit from three plans per patient.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients experiencing severe acute non-genitourinary side effects following radiotherapy. | Acute CTC non-genitourinary toxicity grade 3 or higher. | 12 weeks from start of radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local control | Presence of cancer in the bladder 3 months after treatment | 3 months |