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NCT Number: NCT01810757

Study of Weekly Radiotherapy for Bladder Cancer

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.

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Key information

Conditions

Bladder Cancer Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Male Urogenital Diseases Neoplasms Neoplasms by Site Urinary Bladder Diseases Urinary Bladder Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Addenbrooke's Hospital, Cambridge, United Kingdom

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Standard planning radiotherapy

Radiation

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

Adaptive planning radiotherapy

Radiation

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

Primary outcomes

  1. 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

Secondary outcomes

  1. Local Disease Control Rate

    Time frame: 3 months

    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.

  2. Time to Local Disease Progression

    Time frame: Event-free survival estimates at 12 months and 24 months are reported.

    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.

  3. Overall Survival

    Time frame: Event-free survival estimates at 12 months and 24months are reported.

    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.

  4. The Control Rate of Presenting Symptoms

    Time frame: 3 months from the completion of radiotherapy

    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.

  5. The Proportion of Fractions Benefiting From Adaptive Planning

    Time frame: End of treatment, treatment is given over 6 weeks

    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.

Sponsors and collaborators

Lead sponsor

Institute of Cancer Research, United Kingdom

Other

Collaborators

  • Cancer Research UK

Registry information

Official study title

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

Acronym: HYBRID

Important dates

Study start
2014
Primary completion
2016
Study completion
2023
First posted
Mar 14, 2013
Registry last updated
Jan 15, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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