Vanderbilt Clinical Trials

Conditions

• Muscle Invasive Bladder Urothelial Carcinoma
• Stage II Bladder Cancer AJCC v8
• Stage IIIA Bladder Cancer AJCC v8

Eligibility

Eligible Ages

Over 18 Years

Eligible Sex

All

Accepts Healthy Volunteers

No

Criteria

Inclusion Criteria:

- Histologically proven, cT2-T3,N0M0 urothelial carcinoma of the bladder prior to
randomization.

- Note: Patients with mixed urothelial carcinoma will be eligible for the trial,
but the presence of small cell carcinoma will make a patient ineligible

- Must undergo a transurethral resection of bladder tumor (TURBT) prior to
randomization. Patients may have either completely or partially resected tumors as
long as the treating urologist attempted maximal resection

- Must undergo radiological staging prior to randomization. Imaging of chest, abdomen,
and pelvis must be performed using CT or MRI (with or without contrast is
acceptable). Patients must not have evidence of T4 or node positive disease.
Fluorodeoxyglucose (FDG) PET imaging is acceptable for radiological staging

- If any lymph nodes ≥ 1.0 cm in shortest cross-sectional diameter are noted on
imaging (CT / MRI of abdomen and pelvis), then the patient must have had a biopsy of
the enlarged lymph node showing no tumor involvement prior to randomization

- No diffuse carcinoma in situ (CIS) based on cystoscopy and biopsy

- No definitive clinical or radiologic evidence of metastatic disease

- Must not have had urothelial carcinoma or histological variant at any site outside
of the urinary bladder within 24 months prior to registration except Ta/T1/Carcinoma
in situ (CIS) of the upper urinary tract including renal pelvis and ureter if the
patient had undergone complete nephroureterectomy

- Age ≥ 18

- Zubrod performance status of ≤ 2

- Not pregnant and not nursing

- Negative urine or serum pregnancy test (in persons of childbearing potential)
within 14 days prior to registration. Childbearing potential is defined as any
person who has experienced menarche and who has not undergone surgical
sterilization (hysterectomy or bilateral oophorectomy) or who is not
postmenopausal

- Absolute neutrophil count (ANC) ≥ 1,500 cells/mm^3

- Platelets ≥ 100,000 cells/mm^3

- Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve
hemoglobin [Hgb]) ≥ 8.0 g/dl is acceptable)

- Creatinine clearance (CrCL) of ≥ 30 mL/min by the Cockcroft-Gault formula

- Total bilirubin ≤ 2 x institutional upper limit of normal (ULN)

- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 3 x
institutional ULN

- All adverse events associated with any prior therapy must have resolved to Common
Terminology Criteria for Adverse Events (CTCAE) grade ≤ 3 prior to randomization

- For patients who have completed neoadjuvant therapy, they are eligible if the
pre-neoadjuvant therapy diagnosis (TURBT path) is within 180 days before
randomization

- Must not have had prior pelvic radiation

- New York Heart Association Functional Classification II or better (NYHA Functional
Classification III/IV are not eligible) (Note: Patients with known history or
current symptoms of cardiac disease, or history of treatment with cardiotoxic
agents, should have a clinical risk assessment of cardiac function using the New
York Heart Association Functional Classification.)

- No active infection requiring IV antibiotics

- Patients with hydronephrosis are eligible if they have unilateral hydronephrosis and
kidney function meet criteria specified

Recruiting Locations

Study Contact

Detailed Description

PRIMARY OBJECTIVE: I. Demonstrate non-inferiority of ultra-hypofractionated (stereotactic body radiation therapy [SBRT]) compared to hypofractionated radiation therapy (RT) with a 10% non-inferiority margin (from 50% to 40%) in the rate of bladder-intact event-free survival (BI-EFS) at 3 years (corresponding to a hazard ratio < 1.32). SECONDARY OBJECTIVES: I. Compare the rates of urinary and bowel toxicity, patient-reported outcomes (PRO), event-free survival (EFS), metastasis-free survival (MFS), and overall survival (OS) between the two treatment arms. II. Compare and evaluate symptomatic adverse events and quality of life measures that are most meaningful to patients. III. Evaluate circulating tumor deoxyribonucleic acid (ctDNA) as a biomarker to determine whether it is predictive of disease recurrence and as a secondary outcome variable. EXPLORATORY OBJECTIVES: I. Evaluate ctDNA, tissue-free minimal residual disease (tfMRD) and urine tumor DNA (utDNA) as biomarkers for predicting recurrence. II. Evaluate tfMRD, obtained at the time of progression, to determine if it captures the presence of disease. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive hypofractionated radiation therapy (RT) once daily (QD), Monday to Friday, for 20 treatments in the absence of disease progression or unacceptable toxicity. Patients also receive one of 3 systemic chemotherapy regimens per treating physician's choice: 1) cisplatin intravenously (IV) weekly for 4 weeks; 2) gemcitabine IV on days 1, 4, 8, 11, 15, 18, 22 and 25 or weekly for 4 weeks; or 3) mitomycin-C IV on day 1 and fluorouracil (5 FU), over 120 hours on days 1-5 and 22-26. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) scan and/or magnetic resonance imaging (MRI) or fluorodeoxyglucose (FDG) positron emission tomography (PET) throughout the study. In addition, patients may undergo optional blood and urine sample collection throughout the study, as well as an optional biopsy during cystoscopy during follow up. ARM II: Patients receive ultra-hypofractionated RT QD, no more than twice weekly, for 5 treatments in the absence of disease progression or unacceptable toxicity. Patients also receive one of 3 systemic chemotherapy regimens per treating physician's choice: 1) cisplatin IV weekly for 4 weeks; 2) gemcitabine IV on days 1, 4, 8, 11, 15, 18, 22 and 25 or weekly for 4 weeks; or 3) mitomycin-C IV on day 1 and 5 FU, over 120 hours on days 1-5 and 22-26. Treatment given in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan and/or MRI or FDG PET throughout the study. In addition, patients may undergo optional blood and urine sample collection throughout the study, as well as an optional biopsy during cystoscopy during follow up. After completion of study treatment, patients are followed up at week 16, every 3 months for 3 years then every 6 months to year 5.