3 Participants Needed

Immune Checkpoint Therapy Duration for Bladder Cancer

(IMAGINE Trial)

Recruiting at 395 trial locations
XX
Overseen ByXiao X. Wei, MD, MAS
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: Alliance for Clinical Trials in Oncology
Must be taking: PD-1/L1 inhibitors
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
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 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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on immunosuppressive medication exceeding 10 mg/day of prednisone or its equivalent.

What data supports the effectiveness of the drug Atezolizumab for bladder cancer?

Atezolizumab has been shown to be effective in treating advanced bladder cancer, with a 15% response rate in patients whose cancer progressed after chemotherapy and a 24% response rate in those who were chemotherapy-naïve. It also improved 1-year survival rates to 36% and 57% in these groups, respectively, compared to historical treatments.12345

Is immune checkpoint therapy, like Atezolizumab, generally safe for humans?

Atezolizumab, used for bladder cancer, has shown a favorable safety profile in clinical trials, with most side effects being mild to moderate. Serious side effects were less common, making it generally well-tolerated compared to traditional chemotherapy.13678

How is immune checkpoint therapy with drugs like Atezolizumab different for bladder cancer?

Immune checkpoint therapy drugs like Atezolizumab are unique because they block proteins that prevent the immune system from attacking cancer cells, specifically targeting the PD-L1/PD-1 pathway to boost the body's immune response against bladder cancer. This approach has shown better response rates and survival compared to traditional chemotherapy, especially in patients who have not responded to first-line treatments.13469

Research Team

XX

Xiao X. Wei, MD, MAS

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults with urothelial carcinoma, a type of bladder cancer. Participants must have had at least one cycle of FDA-approved immune therapy and not show disease progression after 12-15 months of treatment. They can't join if they're pregnant, breastfeeding, unwilling to use birth control, or have certain infections or a history of other cancers.

Inclusion Criteria

My cancer is in the bladder, renal pelvis, ureter, urethra, or prostate.
My cancer is advanced but has not been treated with immune therapy yet.
I have undergone at least one treatment cycle with an FDA-approved immunotherapy for my advanced or metastatic bladder cancer.
See 2 more

Exclusion Criteria

No history of allogeneic organ transplantation
I have an autoimmune or inflammatory disorder but don't need more than 10 mg/day of prednisone.
I don't have tuberculosis, hepatitis B or C, or uncontrolled HIV.
See 6 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive immune checkpoint inhibitors such as pembrolizumab, nivolumab, atezolizumab, durvalumab, or avelumab. Treatment cycles repeat every 21 to 42 days depending on the specific drug regimen.

Approximately 1 year

Follow-up

Participants are monitored for overall survival, progression-free survival, and adverse events after treatment completion.

5 years
Follow-up at 4 weeks, then every 6 months

Treatment-free Interval (Arm B)

Participants in Arm B discontinue ICI treatment and may restart upon disease progression at physician discretion.

Varies based on disease progression

Treatment Details

Interventions

  • Atezolizumab
  • Avelumab
  • Durvalumab
  • Nivolumab
  • Pembrolizumab
Trial OverviewThe study compares the effects of stopping immune checkpoint inhibitors (avelumab, durvalumab, pembrolizumab, nivolumab, atezolizumab) after about a year versus continuing them. It aims to see if early discontinuation affects survival rates while reducing side effects and costs.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm B (immune checkpoint inhibitor)Experimental Treatment5 Interventions
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.
Group II: Arm A (immune checkpoint inhibitor)Active Control5 Interventions
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.

Atezolizumab is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Tecentriq for:
  • Melanoma
  • Hepatocellular carcinoma
  • Small cell lung cancer
  • Non-small cell lung cancer
  • Urothelial carcinoma
🇪🇺
Approved in European Union as Tecentriq for:
  • Melanoma
  • Hepatocellular carcinoma
  • Small cell lung cancer
  • Non-small cell lung cancer
  • Urothelial carcinoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials
521
Recruited
224,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Findings from Research

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.
In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.
Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer.Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]
Atezolizumab, an anti-PD-L1 therapy, showed long-term safety and efficacy in patients with metastatic urothelial carcinoma, with a median follow-up of 37.8 months and a low incidence of severe treatment-related adverse events (9%).
The treatment resulted in a 26% objective response rate, with a median duration of response of 22.1 months, and median overall survival of 10.1 months, particularly benefiting patients with higher PD-L1 expression on immune cells.
Atezolizumab (MPDL3280A) Monotherapy for Patients With Metastatic Urothelial Cancer: Long-term Outcomes From a Phase 1 Study.Petrylak, DP., Powles, T., Bellmunt, J., et al.[2022]
In a phase 3 study involving 487 patients with advanced urothelial carcinoma, the combination of pembrolizumab and lenvatinib did not show improved progression-free survival (4.5 months) or overall survival (11.8 months) compared to pembrolizumab with placebo.
The combination treatment resulted in a higher rate of severe adverse events (51%) compared to the placebo group (27%), leading to the conclusion that the benefit-to-risk ratio was not favorable for using lenvatinib with pembrolizumab as first-line therapy.
Pembrolizumab with or Without Lenvatinib as First-line Therapy for Patients with Advanced Urothelial Carcinoma (LEAP-011): A Phase 3, Randomized, Double-Blind Trial.Matsubara, N., de Wit, R., Balar, AV., et al.[2023]

References

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]
Atezolizumab in Patients with Pretreated Urothelial Cancer: a Korean Single-Center, Retrospective Study. [2022]
Atezolizumab (MPDL3280A) Monotherapy for Patients With Metastatic Urothelial Cancer: Long-term Outcomes From a Phase 1 Study. [2022]
Immunotherapy: a new treatment paradigm in bladder cancer. [2021]
Pembrolizumab with or Without Lenvatinib as First-line Therapy for Patients with Advanced Urothelial Carcinoma (LEAP-011): A Phase 3, Randomized, Double-Blind Trial. [2023]
Phase 1 Trial of Atezolizumab Plus Trimodal Therapy in Patients With Localized Muscle-Invasive Bladder Cancer. [2021]
[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. [2019]
Atezolizumab in invasive and metastatic urothelial carcinoma. [2019]
Immunotherapy Beats Chemo for Bladder Cancer. [2018]