Conventionally Fractionated Adaptive Radiation Therapy of Bladder Cancer an Individualized Approach

Study Overview
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Brief Summary
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This is a single-arm, prospective, Phase II, multi-center clinical trial designed to demonstrate that adaptive radiotherapy for muscle invasive bladder cancer will translate into a decreased rate of acute gastrointestinal toxicity compared with the historically reported rate for non-adaptive intensity modulated radiation therapy (IMRT).

Official Title
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Daily Online Adaptive Radiation Therapy of Bladder Cancer for Reduction of Intestinal Toxicity: A Prospective Trial Using an Individualized Approach and Conventional Fractionation (ARTIA-Vesica)

Conditions
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Muscle-Invasive Bladder Carcinoma

Intervention / Treatment
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* Device: Varian Ethos Adaptive Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven bladder cancer Urothelial carcinoma Age ≥ 18 years Stage T1b-T4AN0M0 TUR-B and PET-CT or CT of thorax/abdomen/pelvis within 8 weeks prior to inclusion Suitable for radiotherapy ECOG/WHO performance status 0-2 Written informed consent For Cohort B, participant's must have normal organ and marrow function as defined below: leukocytes ≥2,500/mcL absolute neutrophil count ≥1,500/mcL platelets ≥100,000/mcL hemoglobin ≥9 g/dL total bilirubin ≤ 1,5 ULN AST(SGOT)/ALT(SGPT) ≤3 × ULN alkaline phosphatase ≤2.5 × ULN creatinine clearance <25 ml/min We recommend avoiding cisplatin for participants with creatinine clearance <50 ml/min. INR and aPTT £1.5 ULN Exclusion Criteria: Prior pelvic radiation therapy Inability to comply with the protocol Presence of a hip prothesis Grade 2 or greater baseline diarrhea Uncontrolled inflammatory bowel disease (ulcerative colitis or Crohn's disease)

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daily Adaptive External Beam Radiation Therapy<br>Daily adaptive radiation therapy delivered with Varian Ethos treatment system. | Device: Varian Ethos Adaptive Radiation Therapy<br>* Daily adaptive external beam radiation therapy delivered on Varian Ethos treatment system.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early Rate CTCAE GI Toxicity | Change of the peak early rate of external beam radiation therapy treatment-related (CTCAE) grade 2+ diarrhea | Start of radiotherapy to 3 months after end of radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All Early CTCAE Treatment Related Toxicities | All early adaptive radiation therapy treatment related CTCAE grade 2 and above toxicity | From start of radiotherapy through 3 months after end of radiotherapy | 
| All Late CTCAE Treatment Related Toxicities | All late CTCAE adaptive radiation therapy treatment related toxicity grade 2 and above | From 3 months after end of radiotherapy through 2 years follow-up | 
| Patient Reported Outcomes (PRO) | Collection of NCI PRO-CTCAE questionnaire | Baseline through 2 year follow-up | 
| EORTC Quality of Life Assessment | Collection of EORTC QLQ C30 | Baseline through 2 year follow-up | 
| EuroQol Quality of Life Assessment | Collection EQ-5D-5L questionnaires | Baseline through 2 year follow-up | 
| Local Progression Free Survival | Local progression free survival | From time of inclusion to local progression, assessed up to 24 months post treatment | 
| Local Control | Local control (freedom from local progression) | At 12 and 24 months | 
| Progression Free Survival | Progression free survival (from time of inclusion to disease progression) | From time of inclusion to disease progression, assessed up to 24 months post treatment | 
| Overall Survival | Overall survival | From time of inclusion to death from any cause, assessed up to 24 months post treatment | 
| Disease Free Survival | Disease Free Survival | From time of inclusion to death from bladder cancer, assessed up to 24 months post treatment | 
| Treatment Related Hospitalization | Hospitalization due to adaptive radiation therapy treatment related toxicity | From of start of radiation therapy through 2 year follow-up | 
| Workflow Feasibility | Record percentage of fractions delivered with adaptive radiation therapy vs traditional IGRT | From start of radiation therapy through end of external beam treatment (approximately 6 weeks) |