1190 Participants Needed

Blood Test and Immunotherapy for Bladder Cancer

Recruiting at 396 trial locations
JW
Overseen ByJoseph W. Kim
Age: 18+
Sex: Any
Trial Phase: Phase 2 & 3
Sponsor: National Cancer Institute (NCI)
Must be taking: Immunotherapy
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

What is the purpose of this trial?

This phase II/III trial examines whether patients who have undergone surgical removal of bladder, but require an additional treatment called immunotherapy to help prevent their bladder cancer from coming back, can be identified by a blood test. Many types of tumors tend to lose cells or release different types of cellular products including their DNA which is referred to as circulating tumor DNA (ctDNA) into the bloodstream before changes can be seen on scans. Health care providers can measure the level of ctDNA in blood or other bodily fluids to determine which patients are at higher risk for disease progression or relapse. In this study, a blood test is used to measure ctDNA and see if there is still cancer somewhere in the body after surgery and if giving a treatment will help eliminate the cancer. Immunotherapy with monoclonal antibodies, such as nivolumab and relatlimab, can help the body's immune system to attack the cancer, and can interfere with the ability of tumor cells to grow and spread. This trial may help doctors determine if ctDNA measurement in blood can better identify patients that need additional treatment, if treatment with nivolumab prolongs patients' life and whether the additional immunotherapy treatment with relatlimab extends time without disease progression or prolongs life of bladder cancer patients who have undergone surgical removal of their bladder.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on any immunosuppressive agents or systemic corticosteroids above a certain dose within 14 days before joining the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Nivolumab, Opdivo, Relatlimab, Opdualag, BMS-986016, relatlimab-rmbw for bladder cancer?

Research shows that drugs targeting the PD-1/PD-L1 pathway, like Nivolumab and similar treatments, have been effective in treating advanced bladder cancer. These drugs help the immune system attack cancer cells, and several have been approved for use in bladder cancer, indicating their potential effectiveness.12345

How does the immunotherapy treatment for bladder cancer differ from other treatments?

This treatment is unique because it uses immunotherapy drugs like Durvalumab and Avelumab, which are antibodies that target PD-L1, a protein that helps cancer cells hide from the immune system. Unlike traditional chemotherapy, these drugs enhance the body's immune response to fight cancer, offering a different approach with potentially fewer side effects.12678

Research Team

MD

Matthew D Galsky

Principal Investigator

Alliance for Clinical Trials in Oncology

Eligibility Criteria

This trial is for adults with bladder cancer who've had their bladders and lymph nodes surgically removed recently. It's not for those who only had part of the bladder taken out or have heart failure, severe hearing loss, bad peripheral neuropathy, or poor overall health. Participants should not have any remaining visible cancer after surgery.

Inclusion Criteria

I had a complete bladder removal and lymph node surgery 3 to 12 weeks ago.
I have moderate heart failure.
I can walk and take care of myself but cannot do any physical work.
See 7 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Treatment

Patients receive nivolumab and/or relatlimab intravenously every 28 days for up to 12 cycles

48 weeks
12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years
Visits at weeks 60, 72, 84, 96, 120, 144, 196, and 248

Treatment Details

Interventions

  • Nivolumab
  • Relatlimab
Trial OverviewThe study tests if DNA from tumor cells in blood can guide immunotherapy post-bladder removal surgery. It uses a test called Signatera to detect this DNA and then treats patients with nivolumab alone or combined with relatlimab to prevent cancer recurrence.
Participant Groups
4Treatment groups
Experimental Treatment
Active Control
Group I: Cohort B, Arm IV (ctDNA surveillance, nivolumab)Experimental Treatment7 Interventions
Patients in Cohort B, Arm IV undergo ctDNA surveillance consisting of collection of tissue and blood during screening and collection of blood only on study and during follow up. Patients who convert to ctDNA(+) during surveillance then receive nivolumab IV over 30 minutes and relatlimab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans throughout the trial.
Group II: Cohort A, Arm II (nivolumab, relatlimab)Experimental Treatment7 Interventions
Patients in Cohort A, Arm II receive nivolumab IV over 30 minutes and relatlimab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of tissue during screening and collection of blood throughout the trial. Patients also undergo CT or MRI scans throughout the trial.
Group III: Cohort A, Arm I (nivolumab)Active Control6 Interventions
Patients in Cohort A, Arm I receive nivolumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of tissue during screening and collection of blood throughout the trial. Patients also undergo CT or MRI scans throughout the trial.
Group IV: Cohort B, Arm III (nivolumab)Active Control6 Interventions
Patients in Cohort B, Arm III receive nivolumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of tissue during screening and collection of blood throughout the trial. Patients also undergo CT or MRI scans throughout the trial.

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Findings from Research

Five PD-1/PD-L1 inhibitors are approved for treating advanced bladder cancer, but first-line treatments like Atezolizumab and Pembrolizumab require PD-L1 testing for platinum-ineligible patients, while second-line treatments do not.
The review highlights the differences in PD-L1 testing assays and their implications for clinical practice, providing guidelines to help healthcare professionals navigate the complexities of these tests in urothelial carcinoma.
PD-L1 assessment in urothelial carcinoma: a practical approach.Eckstein, M., Cimadamore, A., Hartmann, A., et al.[2023]
Durvalumab, a monoclonal antibody targeting PD-L1, showed a manageable safety profile in patients with advanced urothelial bladder cancer, with common side effects including fatigue and diarrhea, but no severe (grade 4 or 5) adverse events reported.
The treatment demonstrated a 31% overall response rate, with a significantly higher response of 46.4% in patients with PD-L1-positive tumors, indicating that PD-L1 expression may play a crucial role in the efficacy of durvalumab.
Safety and Efficacy of Durvalumab (MEDI4736), an Anti-Programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor, in Patients With Advanced Urothelial Bladder Cancer.Massard, C., Gordon, MS., Sharma, S., et al.[2022]
The introduction of PD-L1/PD-1 inhibition therapy has significantly changed treatment strategies for advanced urothelial bladder cancer, showing efficacy in both first-line and second-line treatment settings.
Despite the promise of PD-L1/PD-1 therapies, the proportion of patients who actually benefit from these treatments remains low, highlighting the need for better biomarker-driven approaches to improve patient selection and treatment outcomes.
Programmed death ligand-1/programmed death-1 inhibition therapy and programmed death ligand-1 expression in urothelial bladder carcinoma.Yu, WB., Rao, JY.[2020]

References

PD-L1 assessment in urothelial carcinoma: a practical approach. [2023]
Safety and Efficacy of Durvalumab (MEDI4736), an Anti-Programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor, in Patients With Advanced Urothelial Bladder Cancer. [2022]
Programmed death ligand-1/programmed death-1 inhibition therapy and programmed death ligand-1 expression in urothelial bladder carcinoma. [2020]
Integrating angiogenesis signature and tumor mutation burden for improved patient stratification in immune checkpoint blockade therapy for muscle-invasive bladder cancer. [2023]
Unwrapping the genomic characteristics of urothelial bladder cancer and successes with immune checkpoint blockade therapy. [2020]
Systemic Immunotherapy of Non-Muscle Invasive Mouse Bladder Cancer with Avelumab, an Anti-PD-L1 Immune Checkpoint Inhibitor. [2021]
PD-L1 testing in urothelial bladder cancer: essentials of clinical practice. [2021]
Nivolumab for the treatment of bladder cancer. [2021]