Shorter-course versus standard-course radiation with chemotherapy for muscle-invasive bladder cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a randomized phase III trial that compares ultra-hypofractionated stereotactic body radiation therapy (SBRT) to conventional hypofractionated radiation therapy, each given with one of several standard chemotherapy regimens (cisplatin, gemcitabine, or mitomycin-C with 5‑fluorouracil). Patients with cT2–T3, N0, M0 urothelial bladder cancer who have undergone TURBT are randomized to receive either 20 daily hypofractionated RT treatments or a shorter SBRT course, with biospecimen collection for ctDNA and other molecular assays. The primary endpoint is 3-year bladder-intact event-free survival with a non-inferiority margin of 10% (HR < 1.32); secondary endpoints include urinary and bowel toxicity, patient-reported outcomes, EFS, MFS, and overall survival. Exploratory analyses will test ctDNA, tissue-free minimal residual disease, and urine tumor DNA as biomarkers for recurrence and disease detection at progression.

Why it matters

Who can join: the full rules

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 ≥3 cycles of neoadjuvant chemotherapy prior to randomization, this eligibility window from diagnosis (TURBT Path) to enrollment is extended to 240 days before randomization. It remains a 180 day window for all others
* 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

Where it's running

• Fairbanks Memorial Hospital
  Fairbanks, Alaska, United States Recruiting
• Mercy Hospital Fort Smith
  Fort Smith, Arkansas, United States Recruiting
• University of Arkansas for Medical Sciences
  Little Rock, Arkansas, United States Recruiting
• Tower Cancer Research Foundation
  Beverly Hills, California, United States Recruiting
• UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
  Irvine, California, United States Recruiting
• UC San Diego Moores Cancer Center
  La Jolla, California, United States Recruiting

+209 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Principal investigator: Scott E Delacroix — NRG Oncology

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• ctDNA-based monitoring in muscle-invasive bladder cancer

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• Immunotherapy plus radiation to avoid bladder removal after chemo for muscle-invasive bladder cancer

  This phase II test gives pembrolizumab with radiation after chemotherapy to try to help people with muscle-invasive bladder cancer keep their bladders instead of having them removed.

  Recruiting at 171 sites Phase 2 National Cancer Institute (NCI) · Birmingham, Alabama and 181 other locations · NCT07061964

• Combining enfortumab vedotin and pembrolizumab with radiation for muscle invasive bladder cancer

  This study is testing a new combination of a drug and radiation therapy to see if it helps people with muscle invasive bladder cancer who want to avoid surgery.

  Recruiting Phase 1/2 University of California, San Francisco · San Francisco, California · NCT06470282

• Combining futibatinib and durvalumab before bladder cancer surgery for patients who can't use cisplatin

  This study is testing if combining two drugs, futibatinib and durvalumab, before bladder cancer surgery can help patients who can't take cisplatin feel better and improve their chances of recovery.

  Recruiting at 2 sites Phase 2 Ohio State University Comprehensive Cancer Center · Ann Arbor, Michigan and 2 other locations · NCT06263153

• Bladder cancer: test a biomarker-guided plan after neoadjuvant therapy

  This phase 2 study tests a biomarker- and response-guided plan to preserve the bladder in patients with muscle-invasive bladder cancer after neoadjuvant therapy.

  Recruiting Phase 2 Fox Chase Cancer Center · Philadelphia, Pennsylvania · NCT07908979

• Combination treatment for muscle-invasive bladder cancer

  This study is testing a new combination of two medications to see if they can help people with muscle-invasive bladder cancer avoid surgery and improve their treatment outcomes.

  Recruiting at 5 sites Phase 2 Hoosier Cancer Research Network · Duarte, California and 4 other locations · NCT06809140

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.