External Beam Radiotherapy for Muscle Invasive Bladder Cancer

Study Overview
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Brief Summary
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In this phase 1 trial, the investigators will prospectively evaluate 3 different external beam radiotherapy (EBRT) schedules. In every schedule, the whole bladder will be treated to 40 Gray (Gy) in 20 fractions, 5 fractions/week, 4 weeks in total. Based on the summation of abnormalities seen on pre- (initial tumor region) and post transurethral resection zone of fibrosis Diffusion weighted-magnetic resonance imaging (MRI) images the tumor region is delineated and defined as a gross tumor volume (GTV). The GTV will be treated using a simultaneous integrated boost (SIB): without extending the 4-weeks treatment period, 3 different dose levels will be implemented in order to increase the biological equivalent dose (BED), as muscle invasive bladder cancer has been shown to be dose-sensitive.

Detailed Description
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3 different dose levels will be implemented in order to increase the biological equivalent dose (BED), as muscle invasive bladder cancer has been shown to be dose-sensitive. Level 1: 57.6 Gray (Gy) (20 x 2.88 Gy, 5 fractions/week, 4 weeks); BED: 61 Gy. Level 2: 60 Gy (20 x 3.00 Gy, 5 fractions/week, 4 weeks); BED: 64 Gy Level 3: 62.4 Gy (20 x 3.12Gy, 5 fractions/week, 4 weeks); BED: 67 Gy. Fiducials will be implanted at the edges of the postoperative bed during the second transurethral resection of the bladder to improve visualization of the gross tumor volume (GTV) during external beam radiotherapy (EBRT) and consequently improve treatment delivery accuracy. In order to further improve the treatment accuracy, 5 planning Computed Tomographies and plans, with different bladder fillings will be made upfront in our study. During treatment the plan corresponding best with bladder filling at time of EBRT will be selected and delivered.

Official Title
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Muscle Invasive Bladder Cancer: External Beam Radiotherapy as an Alternative for Cystectomy

Conditions
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Toxicity

Intervention / Treatment
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* Radiation: external beam radiotherapy (EBRT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histological proven diagnosis of muscle invasive bladder cancer stage <T3b tumours with pathological lymph nodes after extended pelvic lymph node dissection World Health Organisation performance state 0-2 signed informed consent Exclusion Criteria: contra-indication for Diffusion-Weighted-Magnetic resonance imaging

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All patients receive pelvic EBRT to the lymph nodes located along the common, internal, and external iliac artery; obturator fossa; and presacral nodes.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: external beam radiotherapy: Dose level 1<br>57.6 Gray (Gy) (20 x 2.88 Gy, 5 fractions/week, 4 weeks) | Radiation: external beam radiotherapy (EBRT)<br>* EBRT: 3 dose escalation levels<br>|
| Experimental: external beam radiotherapy: dose level 2<br>60 Gy (20 x 3.00 Gy, 5 fractions/week, 4 weeks) | Radiation: external beam radiotherapy (EBRT)<br>* EBRT: 3 dose escalation levels<br>|
| Experimental: external beam radiotherapy: dose level 3<br>62.4 Gy (20 x 3.12Gy, 5 fractions/week, 4 weeks) | Radiation: external beam radiotherapy (EBRT)<br>* EBRT: 3 dose escalation levels<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by Radiation Therapy Oncology Group toxicity scale |  | 3 months after radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants free from local relapse assessed on cystoscopy and Magnetic Resonance Imaging |  | 12 months after radiotherapy |