A Phase 3 interventional study of Pembrolizumab and Nivolumab in Locally Advanced Bladder Urothelial Carcinoma, Locally Advanced Renal Pelvis Urothelial Carcinoma and Locally Advanced Ureter Urothelial Carcinoma, sponsored by Alliance for Clinical Trials in Oncology. Active, not recruiting at 377 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-03-20.
Sponsored by Alliance for Clinical Trials in Oncology · Phase 3, Interventional, and Treatment
This phase III trial compares survival in urothelial cancer patients who stop immune checkpoint inhibitor treatment after being treated for about a year to those patients who continue treatment with immune checkpoint inhibitors. Immunotherapy with monoclonal antibodies, such as avelumab, durvalumab, pembrolizumab, atezolizumab, and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Stopping immune checkpoint inhibitors early may still make the tumor shrink and patients may have similar survival rates as the patients who continue treatment. Stopping treatment early may also lead to fewer treatment-related side effects, an improvement in mental health, and a lower cost burden to patients.
PRIMARY OBJECTIVE:
I. To compare overall survival (OS).
SECONDARY OBJECTIVES:
I. To compare progression free survival (PFS) by (Response Evaluation Criteria in Solid Tumors) RECIST 1.1 criteria.
II. To compare PFS by immune-related (ir)RECIST criteria. III. To determine treatment-free interval (TFI) after immune checkpoint inhibitor (ICI) discontinuation. (Arm B) IV. To determine the rate of response by RECIST 1.1 criteria after ICI rechallenge. (Arm B) V. To assess adverse events in each study arm by Common Terminology Criteria for Adverse Events (CTCAE) 5.0.
OUTLINE: Patient are randomized to 1 of 2 arms.
ARM A (CONTINUATION OF ICI TREATMENT): Patients receive either pembrolizumab intravenously (IV) over 30 minutes on day 1, nivolumab IV over 30 minutes on days 1 and 15, atezolizumab IV over 30-60 minutes on day 1, durvalumab IV over 60 minutes on days 1 and 15, or avelumab IV over 60 minutes on days 1 and 15. Cycles repeat every 21 or 42 days for pembrolizumab, every 21 days for atezolizumab, and 28 days for nivolumab, durvalumab, and avelumab in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, starting new treatment or withdrawn consent, patients are followed up at 4 weeks, and then every 6 months for 5 years following registration.
ARM B (DISCONTINUATION OF ICI TREATMENT): Patients receiving ICI treatment will discontinue ICI treatment within 1 cycle length after randomization. Cycle length is determined by the ICI regimen the patient is receiving at randomization. At disease progression patients may restart the same ICI treatment they were receiving upon randomization at physician discretion.
After completion of study treatment, patients are followed up at 4 weeks, and then every 6 months for 5 years following registration.
716 studies on the registry are indexed under Carcinoma, Transitional Cell; 201 are open to participants now.
This study's enrollment of 3 is below the median of 49 across 549 interventional studies indexed under Carcinoma, Transitional Cell.
Browse Carcinoma, Transitional Cell studies →Alliance for Clinical Trials in Oncology is the lead sponsor of 499 studies on the registry; 27 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 6 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
Documentation of disease
No history of tuberculosis, active hepatitis B (HBV) or hepatitis C (HCV), or uncontrolled human immunodeficiency virus (HIV)
No current immunosuppressive medication exceeding 10 mg/day of prednisone or its equivalent
* Patients with pre-existing or treatment-emergent autoimmune or inflammatory disorders which do not require systemic immunosuppressive treatment exceeding 10 mg/day of prednisone or its equivalent may be included
REGISTRATION ELIGIBILITY CRITERIA:
No history of tuberculosis, active hepatitis B (HBV) or hepatitis C (HCV), or uncontrolled human immunodeficiency virus (HIV)
CONTINUATION OF ICI TREATMENT: Patients receive either pembrolizumab intravenously (IV) over 30 minutes on day 1, nivolumab IV over 30 minutes on days 1 and 15, atezolizumab IV over 30-60 minutes on day 1, durvalumab IV over 60 minutes on days 1 and 15, or avelumab IV over 60 minutes on days 1 and 15. Cycles repeat every 21 or 42 days for pembrolizumab, every 21 days for atezolizumab, and 28 days for nivolumab, durvalumab, and avelumab in the absence of disease progression or unacceptable toxicity.
Drug: Pembrolizumab · Drug: Nivolumab · Drug: Atezolizumab · Drug: Durvalumab · Drug: Avelumab
DISCONTINUATION OF ICI TREATMENT: Patients receiving ICI treatment will discontinue ICI treatment within 1 cycle length after randomization. Cycle length is determined by the ICI regimen the patient is receiving at randomization. At disease progression patients may restart the same ICI treatment they were receiving upon randomization at physician discretion.
Drug: Pembrolizumab · Drug: Nivolumab · Drug: Atezolizumab · Drug: Durvalumab · Drug: Avelumab
Given IV
Given IV
Given IV
Given IV
Given IV
Overall Survival (OS) Rate at 12 Months
OS is the length of time patients are alive after registering to receive protocol treatment. Patients who are lost to follow-up or are not known to be deceased at the time of study analysis will be censored at the time of last patient contact. Cox models will be used to compare the outcome between the two treatment groups.
Time frame: 12 months
Progression-free Survival (PFS) Rate at 12 Months
Progression-free survival (PFS) is the length of time patients are alive without disease progression. Progression will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Stratified Cox models will be used to compare the outcomes between the two treatment groups.
Time frame: 12 months
Immune-related Progression-free Survival (iPFS) Rate at 12 Months
Immune-related progression-free survival (iPFS) is the length of time patients are alive without immune-related progression. Progression will be assessed using immune related (ir)RECIST criteria. Stratified Cox models will be used to compare the outcomes between the two treatment groups.
Time frame: 12 months
Treatment-free Interval (Arm B)
Treatment-free Interval is the length of time patients are off treatment. A Stratified Cox model will be used to evaluate this outcome.
Time frame: From last dose of immune checkpoint inhibitor (ICI) to initiation of a subsequent systemic treatment or death, assessed up to 5 years
Rate of Response After Immune Checkpoint Inhibitor (ICI) Rechallenge (Arm B)
Rate of response is the percentage of patients with response after re-initiation of immune checkpoint inhibitor (ICI) therapy after progression post-registration. Rate of response will be assessed using RECIST 1.1. A chi-square test (or Fisher's exact test) will be used to determine whether there is an association between the best tumor response prior to trial enrollment and that achieved upon ICI re-challenge.
Time frame: Up to 5 years
Number of Patients Experiencing Grade 3 or Greater Adverse Events (AEs)
Adverse events (AEs) are ailments occurring during treatment. AEs will be assessed using Common Terminology Criteria for Adverse Events version 5.0.
Time frame: 2.5 years
| Milestone | Arm A (Immune Checkpoint Inhibitor) | Arm B (Immune Checkpoint Inhibitor) |
|---|---|---|
| Started | 1 | 2 |
| Completed | 0 | 0 |
| Not completed | 1 | 2 |
| Withdrew: Adverse event | 1 | 0 |
| Withdrew: Withdrawal by subject prior to beginning treatment | 0 | 2 |
OS is the length of time patients are alive after registering to receive protocol treatment. Patients who are lost to follow-up or are not known to be deceased at the time of study analysis will be censored at the time of last patient contact. Cox models will be used to compare the outcome between the two treatment groups.
| percentage of participants | Arm A (Immune Checkpoint Inhibitor) | Arm B (Immune Checkpoint Inhibitor) |
|---|---|---|
| Overall Survival (OS) Rate at 12 Months | 0 | 0 |
Progression-free survival (PFS) is the length of time patients are alive without disease progression. Progression will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Stratified Cox models will be used to compare the outcomes between the two treatment groups.
| percentage of participants | Arm A (Immune Checkpoint Inhibitor) | Arm B (Immune Checkpoint Inhibitor) |
|---|---|---|
| Progression-free Survival (PFS) Rate at 12 Months | 0 | 0 |
Immune-related progression-free survival (iPFS) is the length of time patients are alive without immune-related progression. Progression will be assessed using immune related (ir)RECIST criteria. Stratified Cox models will be used to compare the outcomes between the two treatment groups.
| percentage of participants | Arm A (Immune Checkpoint Inhibitor) | Arm B (Immune Checkpoint Inhibitor) |
|---|---|---|
| Immune-related Progression-free Survival (iPFS) Rate at 12 Months | 0 | 0 |
Treatment-free Interval is the length of time patients are off treatment. A Stratified Cox model will be used to evaluate this outcome.
No measurements were reported for this outcome.
Rate of response is the percentage of patients with response after re-initiation of immune checkpoint inhibitor (ICI) therapy after progression post-registration. Rate of response will be assessed using RECIST 1.1. A chi-square test (or Fisher's exact test) will be used to determine whether there is an association between the best tumor response prior to trial enrollment and that achieved upon ICI re-challenge.
No measurements were reported for this outcome.
Adverse events (AEs) are ailments occurring during treatment. AEs will be assessed using Common Terminology Criteria for Adverse Events version 5.0.
| Participants | Arm A (Immune Checkpoint Inhibitor) | Arm B (Immune Checkpoint Inhibitor) |
|---|---|---|
| Number of Patients Experiencing Grade 3 or Greater Adverse Events (AEs) | 0 | 0 |
Collected over 2.5 years. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm A (Immune Checkpoint Inhibitor) | 0/1 (0%) | 0/1 (0%) | 1/1 (100%) |
| Arm B (Immune Checkpoint Inhibitor) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) |
| Event | Arm A (Immune Checkpoint Inhibitor) | Arm B (Immune Checkpoint Inhibitor) |
|---|---|---|
| FatigueGeneral disorders | 1/1 | 0/2 |
| Rash maculo-papularSkin and subcutaneous tissue disorders | 1/1 | 0/2 |
| Laryngeal inflammationRespiratory, thoracic and mediastinal disorders | 1/1 | 0/2 |
| Papulopustular rashInfections and infestations | 1/1 | 0/2 |
| HyperkeratosisSkin and subcutaneous tissue disorders | 1/1 | 0/2 |
| DiarrheaGastrointestinal disorders | 1/1 | 0/2 |
| FeverGeneral disorders | 1/1 | 0/2 |
| MyalgiaMusculoskeletal and connective tissue disorders | 1/1 | 0/2 |
| Flu like symptomsInfections and infestations | 1/1 | 0/2 |
| Skin and subcutaneous tissue disorders - OtherSkin and subcutaneous tissue disorders | 1/1 | 0/2 |
| Age, Categorical(Participants) | Arm A (Immune Checkpoint Inhibitor) | Arm B (Immune Checkpoint Inhibitor) | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 0 | 1 | 1 |
| >=65 years | 1 | 1 | 2 |
| Sex: Female, Male(Participants) | Arm A (Immune Checkpoint Inhibitor) | Arm B (Immune Checkpoint Inhibitor) | Total |
|---|---|---|---|
| Female | 0 | 0 | 0 |
| Male | 1 | 2 | 3 |
| Ethnicity (NIH/OMB)(Participants) | Arm A (Immune Checkpoint Inhibitor) | Arm B (Immune Checkpoint Inhibitor) | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 1 | 1 |
| Not Hispanic or Latino | 1 | 1 | 2 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Arm A (Immune Checkpoint Inhibitor) | Arm B (Immune Checkpoint Inhibitor) | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 1 | 1 |
| White | 1 | 0 | 1 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 1 | 1 |
| Region of Enrollment(participants) | Arm A (Immune Checkpoint Inhibitor) | Arm B (Immune Checkpoint Inhibitor) | Total |
|---|---|---|---|
| United States | 1 | 2 | 3 |
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Plan to share: Yes
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Alliance for Clinical Trials in Oncology