The following clinical trials represent a selection of key studies currently recruiting patients with bladder cancer for inclusion in investigations of new therapies and new regimens of existing treatments for the disease. Each clinical trial description includes the NLM Identifier to be used as a reference with ClinicalTrials.gov. This information can help oncology practice managers and providers direct eligible patients to one of these clinical trials.
1 Perioperative Pembrolizumab with RC + PLND versus Perioperative Enfortumab Vedotin with RC + PLND versus RC + PLND Alone in Muscle-Invasive Bladder Cancer
The purpose of this phase 3 clinical trial is to evaluate perioperative pembrolizumab (Keytruda) or perioperative enfortumab vedotin (Padcev) with radical cystectomy and pelvic lymph node dissection (RC + PLND) versus RC + PLND alone in patients with cisplatin-ineligible muscle-invasive bladder cancer. Patients aged ≥18 years with histologically confirmed muscle-invasive bladder cancer with predominant urothelial histology, clinically nonmetastatic bladder cancer, have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2, and who are ineligible for treatment with cisplatin may be eligible for enrollment if other criteria are met. Eligible patients will receive intravenous (IV) pembrolizumab 200 mg given on day 1 of each 21-day cycle or IV enfortumab vedotin 1.25 mg/kg given on days 1 and 8 of each 21-day cycle with RC + PLND, or RC + PLND alone.
The primary outcome measure is pathologic complete response (pCR) rate in all patients and those with PD-L1 expression within 3 months, and event-free survival (EFS) in all patients and those with PD-L1 expression within 5.5 years. Secondary outcome measures are overall survival (OS), disease-free survival (DFS), pathologic downstaging, and the number of adverse events and discontinuations in patients due to adverse events in all patients and those with PD-L1 expression. This study expects to enroll 836 participants throughout the United States and internationally. For more information, contact
2 Pembrolizumab After Surgery for Localized Muscle-Invasive Bladder Cancer and Locally Advanced Urothelial Cancer
The purpose of this randomized phase 3 clinical trial is to study the efficacy of pembrolizumab in patients with muscle-invasive bladder cancer or locally advanced urothelial cancer versus observation only in these patients. Patients aged ≥18 years with histologically confirmed muscle-invasive urothelial carcinoma of the bladder, urethra, upper tract, or lymph node positive disease, who have gone through transurethral resection or radical cystectomy with no residual cancer or metastatic disease; and have an ECOG performance status of ≤2; and those who have had no previous treatment with PD-1 or PD-L1 agents may be eligible if other criteria are met. Eligible patients will be randomized to receive IV pembrolizumab given over 30 minutes on day 1 repeating every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity or observation only.
The primary outcome measures are OS and DFS within 5 years. The secondary outcome measures are OS and DFS in PD-L1−positive and −negative patients within 5 years. Patients will be compared on global quality of life as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) questionnaire, urinary symptoms, patient-reported adverse events and side effects, and quality-adjusted life-years between the pembrolizumab arm and observation arms. This study expects to enroll 739 patients throughout the United States and Guam. For more information, contact Marissa Mallek at the National Cancer Institute at
3 Nivolumab plus Bempegaldesleukin versus Nivolumab Alone versus Standard of Care for Bladder Cancer
The purpose of this randomized phase 3 clinical trial is to determine whether nivolumab (Opdivo) plus bempegaldesleukin (Bempeg) or nivolumab alone, before and after cystectomy, is more effective than surgery alone in patients with cisplatin-ineligible muscle-invasive bladder cancer. Patients aged ≥18 years with stage II-IVa muscle-invasive bladder cancer diagnosed by transurethral resection of bladder tumor, who are deemed eligible for radical cystectomy, have an ECOG performance status of 0 or 1, and who are deemed ineligible to receive cisplatin treatment may be eligible if other criteria are met. Eligible patients will be randomized to receive neoadjuvant nivolumab plus bempegaldesleukin followed by adjuvant nivolumab plus bempegaldesleukin after radical cystectomy; neoadjuvant nivolumab followed by adjuvant nivolumab alone after surgery; or radical cystectomy alone without neoadjuvant or adjuvant therapy.
Primary outcome measures include pCR rate in neoadjuvant nivolumab combination versus standard of care in all randomized patients and EFS in neoadjuvant and adjuvant nivolumab combination after surgery versus standard of care. Secondary outcome measures include OS, incidence of serious adverse events leading to discontinuation, incidence of immune-mediated adverse events, and incidence of laboratory abnormalities. This study expects to enroll 540 patients throughout the United States and internationally. For more information, contact the recruiting sites directly or e-mail
4 Nivolumab plus Bacillus Calmette-Guérin Combination in High-Risk Nonmuscle-Invasive Bladder Cancer
The purpose of this randomized, double-blind, phase 3 clinical trial is to assess the safety and efficacy of nivolumab plus Bacillus Calmette-Guérin (BCG) versus BCG alone in patients with high-risk nonmuscle-invasive bladder cancer. Patients aged ≥18 years with predominant histologic urothelial carcinoma and histologically confirmed persistent or recurrent high-risk nonmuscle-invasive urothelial carcinoma, who have had recurrent disease ≤24 months since last BCG dose that is not classified as BCG unresponsive, and who have an ECOG performance status ≤2 may be eligible if other criteria are met. Eligible patients will be randomized to receive nivolumab on specific days with intravesical BCG or placebo plus intravesical BCG.
The primary outcome measure is EFS within 3 years. Secondary outcome measures include worsening-free survival, OS, complete response rate, duration of response, incidence of adverse events leading to discontinuation, incidence of immune-medicated adverse events, and incidence of deaths. This study plans to enroll 700 patients throughout the United States and internationally. For more information, contact the recruiting sites directly or e-mail