Enfortumab Vedotin with Concurrent Radiation Therapy for the Treatment of Locally Advanced Bladder Cancer, CONSOLIDATE Trial

Inclusion Criteria

• PRIOR TO CORE ENROLLMENT: Pathologically confirmed diagnosis of urothelial carcinoma of the bladder including patients with T4N0 and T1-4N2 3 disease. Patients with mixed urothelial carcinoma of bladder will also be included
• PRIOR TO CORE ENROLLMENT: Be ≥ 18 years of age on the day of signing informed consent
• PRIOR TO CORE ENROLLMENT: Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * NOTE: If subject is unable to walk due to paralysis, but is mobile in a wheelchair, subject is ambulatory for the purpose of assessing their performance status
• PRIOR TO CORE ENROLLMENT: Hemoglobin ≥ 9 g/dL
• PRIOR TO CORE ENROLLMENT: Platelet count ≥ 100 x 10^9 g/dL
• PRIOR TO CORE ENROLLMENT: Creatinine clearance (CrCl) ≥ 30 mL/min as estimated per institutional standards (glomerular filtration rate [GFR] can also be used instead of CrCl)
• PRIOR TO CORE ENROLLMENT: Absolute neutrophil count (ANC) ≥ 1500/mm^3
• PRIOR TO CORE ENROLLMENT: Male patients must consistently use highly effective methods of birth control starting at screening and continue throughout study period and for at least 6 months after radiation completion
• PRIOR TO CORE ENROLLMENT: Female patients must consistently use highly effective methods of birth control starting at screening and continue throughout the study period and for at least 6 months after radiation completion
• FOLLOWING CORE ENROLLMENT: Candidate for definitive local therapy to active disease per the discretion of the treating physicians

Exclusion Criteria

• PRIOR TO CORE ENROLLMENT: Has a diagnosis of active scleroderma, lupus, ulcerative colitis, or other rheumatologic disease which in the opinion of the treating radiation oncologist precludes safe radiation therapy
• PRIOR TO CORE ENROLLMENT: Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial as determined by the treating physician and/or member of the study team
• PRIOR TO CORE ENROLLMENT: Distant metastatic disease beyond lymph node metastases, which by the discretion of the treating physician cannot be treated definitively in a radiation field
• PRIOR TO CORE ENROLLMENT: Has history of prior pelvic radiation therapy
• PRIOR TO CORE ENROLLMENT: Has ongoing clinically significant toxicity (grade 2 or higher with exception of alopecia) associated with prior systemic therapy
• PRIOR TO CORE ENROLLMENT: History of uncontrolled diabetes mellitus within 3 months of enrollment. Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) ≥ 8% or HbA1c between 7 and < 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained
• PRIOR TO CORE ENROLLMENT: Has estimated life expectancy of less than 12 weeks
• PRIOR TO CORE ENROLLMENT: Has preexisting sensory or motor neuropathy grade ≥ 2
• PRIOR TO CORE ENROLLMENT: Patients receiving ongoing systemic intravenous antimicrobial treatment for active infection at time of randomization
• PRIOR TO CORE ENROLLMENT: Patients have a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as hepatitis C virus ribonucleic acid [HCV RNA] [qualitative] is detected) infection. No testing for hepatitis B and hepatitis C is required unless mandated by local health authority
• PRIOR TO CORE ENROLLMENT: Has a known history of human immunodeficiency virus (HIV) infection. Testing is not required unless mandated by the local health authority
• PRIOR TO CORE ENROLLMENT: Has conditions requiring high doses of steroids (> 10 mg/day of prednisone or equivalent) or other immunosuppressive medications are excluded. Inhaled or topical steroids are permitted in the absence of active autoimmune disease. Physiologic replacement doses of corticosteroids are permitted for subjects with adrenal insufficiency
• PRIOR TO CORE ENROLLMENT: Has a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
• PRIOR TO CORE ENROLLMENT: Has received a prior allogeneic stem cell or solid organ transplant
• PRIOR TO CORE ENROLLMENT: Has active tuberculosis
• FOLLOWING CORE ENROLLMENT: Is pregnant or expecting to conceive within the projected duration of the trial at the screening visit * Female subject of childbearing potential should have a negative urine or serum pregnancy within 6 weeks prior to study registration up to the first fraction of radiation * Note: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required