Adjuvant Proton Therapy or IMRT for the Treatment of Bladder Cancer

Study Overview
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Brief Summary
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Invasive urothelial bladder cancer is a common malignancy causing 14,000 deaths annually in the United States. The primary objective of the feasibility/Phase I portion of the study is to establish the feasibility and safety of proton and the safety of IMRT for patients with pure or mixed variant urothelial carcinoma.

Detailed Description
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Invasive urothelial bladder cancer is a common malignancy causing 14,000 deaths annually in the United States. The primary objective of the feasibility/Phase I portion of the study is to establish the feasibility and safety of proton and the safety of IMRT. Safety will be based on acute toxicity. The primary objective of the phase II study is to generate estimates of the local failure rate for intermediate and high risk patients treated with either proton therapy or IMRT. The study, however, is not explicitly designed to compare outcomes of proton therapy and IMRT. Secondary objectives include further evaluation of acute and late toxicity, quality of life and estimation of overall survival.

Official Title
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Feasibility and Phase 1/II Trial of Adjuvant Radiation Therapy for the Treatment of Urothelial Bladder Cancer Using Proton Therapy or IMRT

Conditions
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Urothelial Carcinoma of the Bladder

Intervention / Treatment
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* Radiation: Proton therapy
* Radiation: IMRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pure or mixed variant urothelial carcinoma o Allowable mixed variant subtypes include: squamous differentiation glandular differentiation nested pattern microcystic micropapillary lymphoepthelioma-like plasmacytoid and lymphoma-like sarcomatoid/carcinosarcoma giant cell trophoblastic differentiation clear cell lipid cell undifferentiated Radical cystectomy and pelvic lymph node dissection within the prior 48 weeks Pathologic T3 or higher stage disease, N0-2, M0 (AJCC, 7th Ed., Appendix C) No clinical evidence of residual or recurrent disease based on the following minimum diagnostic work-up within 8 weeks of a patients consent to participate. History and physical examination Chest imaging by x-ray (PA and lateral views) or CT scan (with or without IV contrast); Axial abdominal and pelvic imaging by MRI (preferably with gadolinium) Bone scan Patients with microscopically involved (positive) surgical margins, but no grossly evident residual disease by imaging or physical exam are eligible. The patient is a candidate for definitive external beam radiotherapy; No prior radiotherapy to the region of study; No inflammatory bowel disease, active collagen vascular or connective tissue disorders, and no other medical or social contraindications to radiotherapy, as determined by a participating radiation oncologist; Age ³18 years ECOG performance status: 0-2 Concurrent noninvestigational medications will be permitted Informed consent: Patients must have the ability to understand and be willing to sign the study-specific informed consent indicating their understanding of the investigational nature and the risks of this study before any of the protocol related studies are preformed (this does not include routine laboratory testing or imaging studies required to establish study eligibility); Exclusion Criteria: Unstable renal function in the month prior to registration defined as a creatinine rise of 1 mg/dL Prior partial or complete small bowel obstruction either before or after radical cystectomy Prior radiotherapy to the pelvis; o Prior radiation therapy for a different cancer or disease process is allowed, provided there will be no overlap of radiation therapy fields between the participants prior and current course of radiation therapy, radiotherapy was completed more than four weeks from enrolling in this study. Planned concurrent chemotherapy or other investigational drug to be given with radiation treatments o Prior chemotherapy or investigational drug for bladder cancer or a different cancer is allowed, provided that: The therapy was completed more than two weeks prior to the start of adjuvant pelvic radiation The participant has recovered to Grade 1 toxicity from agents previously administered Subtotal surgical resection with clinically evident residual disease by physical exam or axial imaging. Prior or concurrent second invasive malignancy other than prostate and non-melanoma skin cancers, unless disease free for a minimum of five years. If a patient had a concurrent prostate cancer, then it must have been resected to negative margins. Known severe, active co-morbidity, defined as follows: o Any clinically significant unrelated systemic illness, medical condition, or other factor, which at the discretion of the Principal Investigators, would interfere in the safe and timely completion of study procedures, compromise the patients ability to tolerate the protocol therapy, or is likely to interfere with the study procedures or results.

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

| Intervention/Treatment |
| --- |
|Radiation: Proton therapy|nan|
|Radiation: IMRT|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Applies to Proton only | withion 14 days of estimated date of treatment completion | 
| Number of Participants With Adverse Events | Applies to Both Proton and IMRT | within 90 days of radiation therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Late toxicty | later than 90 days from start of radiation therapy |