NCT04637594

Trying to Find the Correct Length of Treatment With Immune Checkpoint Therapy

Duration of Immune Checkpoint Therapy in Locally Advanced or Metastatic Urothelial Carcinoma: A Randomized Phase 3 Non-Inferiority Trial (IMAGINE)

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: Alliance for Clinical Trials in Oncology · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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 After completion of study treatment, starting new treatment or withdrawn consent, patients are followed up at 4 weeks, and then every 6 months for 5 years following registration.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.

Conditions

• Locally Advanced Bladder Urothelial Carcinoma
• Locally Advanced Renal Pelvis Urothelial Carcinoma
• Locally Advanced Ureter Urothelial Carcinoma
• Locally Advanced Urethral Urothelial Carcinoma
• Locally Advanced Urothelial Carcinoma
• Metastatic Bladder Urothelial Carcinoma
• Metastatic Renal Pelvis Urothelial Carcinoma
• Metastatic Ureter Urothelial Carcinoma
• Metastatic Urethral Urothelial Carcinoma
• Metastatic Urothelial Carcinoma

Interventions

Type	Name	Description
DRUG	Pembrolizumab	Given IV
DRUG	Nivolumab	Given IV
DRUG	Atezolizumab	Given IV
DRUG	Durvalumab	Given IV
DRUG	Avelumab	Given IV

Timeline

• Start date: 2022-05-27
• Primary completion: 2024-06-01
• Completion: 2030-09-01
• First posted: 2020-11-20
• Last updated: 2026-03-20
• Results posted: 2026-03-20

Locations

377 sites across 1 country: United States

Regulatory

• FDA-regulated drug study